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ffe ~R B m 

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COPYRIGHT DEPOSIT. 



A TEXT- 

oj 

PATHO 



BOOK 

LOGY 



BY 

ALFRED STENGEL, M. D., Sc. D. 

Professor of Medicine, University of Pennsylvania; Physician to the Pennsylvania 
and to the University Hospitals 



AND 



HERBERT FOX, M. D. 

Director of the Pepper Laboratory of Clinical Medicine, University of Pennsyl- 
vania; Pathologist to the Philadelphia Zoological Garden 



SEVENTH EDITION, RESET 



WITH 509 TEXT ILLUSTRATIONS, MANY 
IN COLORS, AND 15 COLORED PLATES 



PHILADELPHIA AND LONDON 



W. B. SAUNDERS COMPANY 

1921 




Copyright, 1898, by W. B. Saunders. Revised, reprinted, and recopyrighted March, 1899. 
Reprinted August, 1899; November, 1899. Revised, reprinted, and recopyrighted 
October, 1900. Reprinted July, 1901; September, 1902. Revised, reprinted, 
and recopyrighted July, 1903. Reprinted March, 1905. Revised, 
reprinted, and recopyrighted September, 1906. Reprinted 
November, 1907; August, 1909; August, 1910; July, 
1911, and June, 1912. Revised, entirely reset, 
reprinted, and recopyrighted August, 1915. 
Reprinted February, 191 9. Revised, 
entirely reset, reprinted and re- 
copyrighted April, 1 92 1. 



Copyright, 1921, by W» B. Saunders Company 



§>CI. 



U617015 



PRINTED IN AMERICA 




PREFACE TO THE SEVENTH EDITION 



The present edition of the Text Book of Pathology follows the style 
of previous issues in presenting the matter in paragraphic reference 
form, although so much new matter has been added and so extensive a 
revision of every section has been made necessary by the rapid increase in 
pathologic knowledge during late years, that a complete resetting of the 
whole book was decided upon. The additions however have been in the 
direction of new matter and detail, with a careful avoidance of specula- 
tion and controversy, the attempt being to give the practitioner and 
student a conservative defensible opinion of the subject as it is understood 
today. 

Some entirely new sections have been added; several important 
headings, such as those dealing with nephritis, influenza and lymphomata, 
have been rewritten. Replacements and additions of illustrations to the 
extent of about a hundred have been provided. Our thanks are offered 
to the publishers for their helpful attitude in making the revisions as 
complete as we could desire. 

Alfred Stengel. 
Philadelphia, Pa., Herbert Fox. 

April, 1921. 



13 



CONTENTS 



PART I— GENERAL PATHOLOGY 



Paoe 



CHAPTER I 

The Etiology of Disease 19 

CHAPTER II 

Disorders of Nutrition and Metabolism 41 

CHAPTER III 

Disturbances of the Circulation of the Blood 60 

CHAPTER IV 

Retrogressive Processes 82 

CHAPTER V 

Inflammation and Regeneration 121 

CHAPTER VI 

Progressive Tissue Changes 163 

CHAPTER VII 

Teratology. 246 

CHAPTER VIII 

Bacteria. Their Nature and Action 253 

CHAPTER IX 

Diseases Due to Bacteria 286 

CHAPTER X 

Animal Parasites and Diseases Caused by Them . 382 

CHAPTER XI 

The Methods of Transmission of the Communicable Diseases 423 

PART II— SPECIAL PATHOLOGY 

CHAPTER I 

Diseases of the Blood 429 

CHAPTER II 

Diseases of the Lymphatic Tissues 459 

15 



16 



CONTENTS 



Page 

CHAPTER III 

Diseases of the Circulatory System 4g4 

CHAPTER IV 

Diseases of the Respiratory System 549 

CHAPTER V 

Diseases of the Gastro-intestinal Tract 622 

CHAPTER VI 

Diseases of the Ductless Glands 734 

CHAPTER VII 

Diseases of the Urinary Organs 753 

CHAPTER VIII 

Diseases of the Reproductive Organs . . 811 

CHAPTER IX 

Diseases of the Bones 883 

CHAPTER X 

Diseases of the Joints 903 

CHAPTER XI 

Diseases of the Voluntary Muscles 912 

CHAPTER XII 

Diseases of the Brain and Its Membranes 920 

CHAPTER XIII 

Diseases of the Spinal Cord and Its Membranes 978 

CHAPTER XIV 

Diseases of the Peripheral Nervous System 1006 

CHAPTER XV 

The Eye 1012 

CHAPTER XVI 

The Ear. . < 1033 

CHAPTER XVII 

The Skin .................. * 1040 

Index 1061 



A TEXT-BOOK OF PATHOLOGY 



PART I 
GENERAL PATHOLOGY 



Pathology is the science that deals with disease in all its aspects. 
It includes the study of the causes, the manifestations, and the results 
of disease. 

Three important subdivisions of the study of pathology are recog- 
nized, viz., etiology y or the study of the causes of disease; morbid or 
pathological anatomy, the study of the gross and microscopical structural 
changes in disease; and morbid or 'pathological physiology, the study of 
disturbances of function. In the latter groups is included pathological 
chemistry, as morbid chemical action and its results are the outcome 
of disturbed function. 

Pathology may be otherwise divided into general and special pathology. 
The former treats of causes of disease and pathological processes irre- 
spective of any individual part; the latter deals with the causes or 
processes in individual diseases, organs, or parts. 

Disease itself is not a separate entity, but may be denned as ab- 
normality in structure, in function, or in both combined. It is doubt- 
ful whether alteration of function can occur without some alteration 
in structure, but it frequently happens that functional disturbances 
are present though no structural alterations are discoverable even by 
the most precise methods of investigation. 

It is obvious from the foregoing that it is impossible to define sharply 
either disease or health. Health, or fully harmonious action of all 
physical and physiological units, is subject to the same laws of mode and 
mean as any other group of varying but comparable units, and as the 
examples or phenomena digress from the mean, they approach the 
abnormal or the unnatural. This will suggest the merging of the healthy 
into the diseased state, and it must be understood that in digressing from 
a norm in the developmental or adult state, the animal body does not give 
evidence of new structures or functions. Such anatomical changes as may 
take place are in the direction of reversion to a fetal or undifferentiated 
tissue and chemical abnormalities are in the form of incomplete or irregular 
metabolism. Assuming further that health is controlled by a harmoni- 
ous and uniform set of impulses, the interruption of one of them or the 
introduction of a foreign stimulus will unbalance the cycle, or the natural 
impulses may be destroyed by the foreign intrusion. Many slight abnor- 
malities of stimulation or minor intrusions are quickly removed and the 
2 17 



18 



A TEXT-BOOK OF PATHOLOGY 



general physiology rights itself promptly. If, however, the interruption 
or intrusion affect an important structure, an organ like the liver or lung, 
the cycle of physiology of the remaining parts must be constructed upon a 
temporary plan in a compensatory manner. The various organs or 
systems have different values in throwing compensatory work upon others. 
For example, the failing lung throws work upon the kidneys, skin, and 
intestines, and the failing heart strains the lungs and kidneys. Organs in 
pairs complement each other or one may attempt to assume the duties of 
both. The loss of the liver or kidneys is incompatible with life, while a 
large part of these organs or even of the brain may be destroyed without 
cessation of life. 

The character of an organ, grossly, microscopically and chemically, 
being dependent upon its constituent cells, the alteration in diseased 
organs is fundamentally the effect of pathological changes in such cells, as 
Virchow's philosophy has taught us. There exists within organs as be- 
tween different organs, a balance of function, nicely adjusted and adapted 
not only to interorganic structure and function but to the role of other 
viscera perhaps through circulating messengers acting as mutual regu- 
lators. The severity of an abnormality stands in direct relation to the 
number of cells affected, the degree of change, and the importance of the 
cells. The more highly specialized a cell, the less able it is to regenerate 
its kind, and, therefore, the more lasting is the effect of its destruction. 
The cells of the brain and the germ cells do not reproduce. 

It cannot be maintained today that disease is primarily either cellular 
or functional but it is reasonably certain that no physical change occurs 
without its corresponding chemical alteration and it is difficult to under- 
stand a metabolic disturbance without an anatomical one. The cause of 
the anatomical and chemical changes are factors either within or without 
the body. The specific diseases are usually indicated by an equally 
specific set of anatomical and chemical changes from the normal. The 
foregoing paragraphs illustrate the problem of pathology as a biological 
one to be approached in the broadest possible manner. The student 
must not be satisfied with thinking that a diagnosis depends upon what 
may be seen under a microscope or upon a kymograph, he must weigh all 
the facts that can be mustered and be a constant student of anatomy, 
gross and minute, physiology, normal and abnormal, and of chemistry in 
all its branches. 

The symptoms of disease are the expressions of abnormal functional 
activity, and are, therefore, properly discussed under the head of Patho- 
logical Physiology; but they are so important from a practical stand- 
point, and form so extensive a subject of investigation, that they are 
usually considered apart from pathology, in special treatises dealing with 
diagnosis and the practice of medicine. 



CHAPTER I 



THE ETIOLOGY OF DISEASE 

The study of the causation of disease embraces and must account 
for the predisposing factors and the determining causes. The former 
prepare the system and make it susceptible to the latter, or immediate 
and specific causes of disease. 1 

The predisposing factors may increase the receptivity of the body for 
more than one kind of disease agent. The term " predisposition " is 
at times used for a hereditary or acquired tendency toward certain 
diseased states. Thus, one might exemplify hereditary predisposition 
by the lowered resistance to tuberculosis of the young of tuberculous 
parents. Another phase of this hereditary influence is shown in the 
tendency for cells to exhibit an abnormal metabolism because of a family 
or hereditary tendency, and leading to abnormal states of health (Baum- 
garten's anlage). (See Heredity.) Acquired predisposition is due to 
vices of living, previous disease, or to a summation of several 
predisposing factors leading in one direction. This has been termed 
''disposition 7 ' by some writers. 

Predisposing Factors. — The normal system is able to cope with 
the determining causes of disease to a certain point by its general vitality 
and regulative functions. Thus, heat and cold may prove harmless if not 
too intense or prolonged. In the case of exposure tc heat, the superficial 
capillaries become dilated, sweating increases, and there is increased heat 
dissipation from the surface at the same time that increased respiratory 
function occasions evaporation and loss of heat through the lungs. In 
the case of exposure to cold, increased muscular exercise leads to greater 
heat production, while contraction of the superficial blood-vessels restricts 
the elimination of heat. When, however, a certain point of intensity is 
reached in the case of heat, cold, or other causes of disease, the normal 
organism is unable to oppose sufficient resistance, and disease or injury 
results. Chemical relations in body cells and fluids,, such as equilibrium 
of colloids in solid and liquid condition or enzyme power, may be de- 
stroyed by prolonged exposure to heat and cold, and the former may also 
destroy red blood-cells. The degree of resistance differs in different 
individuals, in different races, or people living under varying climatic 
conditions, etc. In some the degree of resistance may be so great that 
certain diseases are never contracted. The term immunity (q. v.) is 
applied to this state. 

Certain predisposing factors may now be taken up in order. 

1. Age. — This plays a large part in the vulnerability of an individual. 
The exanthemata are much more common in childhood, while car- 
cinoma is commonest in adult life. The rate of repair is also greater in 

19 



20 A TEXT-BOOK OF PATHOLOGY 

youth. Tuberculosis assumes somewhat different forms when develop- 
ing in childhood, adolescence, or adult life. There is a decided varia- 
tion in the amount of protective antibody in the blood at different ages. 

2. Sex. — The influence of sex is not great aside from disease of the 
sexual organs. Man is subject to more traumatisms and diseases due to 
the wider social life he leads. He suffers more often from cancer, aside 
from genitalia, than the female. There are more cases of gout, diabetes, 
and organic nervous disease in men. Women are more often attacked 
by functional nervous diseases and affections of the thyroid gland. 

3. Race. — Certain peoples are prone to or immune against certain 
diseases. Negroes are resistant to malaria and endure yellow fever 
well. Aside from the unsanitary conditions in which many live, they 
have a low resistance to tuberculosis. The effect of zoological order is 
more pronounced than race differences. The dog is resistant to tuber- 
culosis; the chicken, to tetanus. This has hampered experimental work 
upon infectious diseases, because it is often difficult to fulfil Koch's pos- 
tulates (q. v.). 

4. Nutrition. — Failure to obtain wholesome pure food will, of course, 
reduce resistance. The presence of putrefaction or disease-producing 
agents will cause disease. Prolonged hunger reduces general resistance. 

When food of sorts to which people are accustomed become unavail- 
able, substitutions must of course be made and the use of these may lead 
to chronic digestive disorders; the eating of unusual foods has the same 
effect. Habits, like that of alcoholic liquor drinking, may reduce the 
resistance by disturbing digestion. Proper fat rationing or at 
least the necessary calorie requirement of the body must be maintained, 
in order that normal resistance continues. The relation of bodily activity 
and stored-up reserve has an influence upon later demands of exertion. 

Not only is the availability of nourishment of importance to the body 
as a whole but it must be maintained to each part proportionately, for 
deprivation of pabulum by arterial obstruction may lead to atrophy or 
functional disorders. 

5. Idiosyncrasy is the peculiar susceptibility of individuals to cer- 
tain poisons or infections and sometimes even to ordinary foods. This 
should not be confused with diathesis or predisposition (q. v.). 

The presence of one infection may favor the reception of another. 

6. Conditions of Life. Habitation in places infested with disease-trans- 
mitting insects materially influences morbidity. Unsanitary dwellings 
directly affect health usually by the resulting anemia, with a consequent 
reduction of resistance especially to communicable disease. Occupation 
is for the most part potent in the predispositions or causation of disease 
by what is inhaled (coal dust, hair feathers) or swallowed (lead) or by the 
position in which work is done (tailors) . Prolonged mental anxiety has 
some depressing effect upon resistance and has a pronounced 
influence in the production of psychosis particularly in those so inclined. 
There seems fair reason to assume that continued nervous strain may have 
some effect in arterial degenerations and sudden shock has been known to 
precipitate glycosuria. 

7. Injury. 

8. Heat and cold. 



THE ETIOLOGY OF DISEASE 



21 



9. Physical forces, like electricity and x-ray, and atmospheric pressure. 

10. Poisons of all kinds. 

Items 1 to 5 may be called intrinsic or internal, while 6 to 10 are 
extrinsic or external. 

PATHOLOGICAL DISPOSITION 

Under this heading come those instances in which physical or phy- 
siological departures from the type or from the standard are expressed 
in the unusual susceptibility of the whole or a part. Idiosyncrasies 
might be classed here.. This pathological disposition refers chiefly to 
those conditions in which slow healing of skin wounds or the lack of 
sweat and sebaceous secretions render the skin more susceptible to 
spreading infections. We might also include here the sensitive state of 
some individuals to certain organic proteins which makes them subject 
to intoxications with these compounds, not toxic to other persons. (See 
Anaphylaxis.) 

There is a related pathological disposition at seats of chronic in- 
flammation, chronic irritation, or chronic injury, as it has lately been 
called. Here malignant change may occur. 

Whether this pathological disposition is hereditary or acquired is 
difficult to say, as it is equally impossible to decide whether it is due to 
absence of immunity reactions. 

Occasionally organ or system disposition is mentioned, by which is 
meant a peculiar visceral distribution of lesions, which may be anatom- 
ical or physiological. It covers such instances as the frequency of 
infarction of the spleen and lung, and the involvement of the spleen' in 
liver disease. 

Heredity or inheritance is a factor of importance in the etiology of 
disease but there is some question as to the true inheritance of a special 
condition. It would seem better to consider the prenatal influence in two 
ways: First as' the result of a physiology and perhaps anatomy that has 
been following a certain course of events for some generations and the 
young must needs continue this same scheme (this is shown in familial 
gout) or second, where the offspring is the result of an established patho- 
logical parent and when it appears in the world is at once surrounded 
by conditions favoring the development of disease (illustrated by tuber- 
culosis). Also, an alcoholic mother or one subjected to hardships during 
pregnancy may give birth to a child which is feeble and lacking in re- 
sistance to disease; this feebleness is congenital, but not inherited. The 
same statement applies to diseases such as tuberculosis and syphilis, which 
may be acquired from the mother by the the fetus in utero, but are not 
inherited. If the father is the original source of infection, he first infects 
the mother, from whom the child then acquires the disease. One cannot 
in these cases properly use the term " hereditary." 

Heredity, strictly speaking, applies only to the transmission of 
parental or ancestral characteristics to the offspring through the paren- 
tal germ-plasm. We may distinguish between racial, familial, and 
direct inheritance. The term direct inheritance indicates transmission 
from parent to offspring. The term indirect is sometimes used to indicate 
transmission of characters latent in one generation to subsequent ones. 



22 



A TEXT-BOOK OF PATHOLOGY 



Atavism is a more frequent designation of this derivation of characteristics 
from ancestors after they had been latent in one or more generations. 
In a broader sense the term "atavism" has also been applied to reversion to 
racial characteristics that had been dormant through man}?- generations. 
Collateral inheritance is a term used in cases in which an individual mani- 
fests characters present in uncles, aunts, or other collaterals, but not in his 
parents or immediate ancestors. The laws of heredity explain this 
occurrence. 

In some cases there is crossed transmission. A peculiar form of 
heredity is seen in hemophilia and some other diseases, which are trans- 
mitted through the female members of a family, who generally remain 
unaffected, to the male offspring. Hereditary traits sometimes pre- 
dispose to a number of allied affections. This is particularly striking 
in the case of the neuropathic heredity, in which various forms of nervous 
disease may appear alternately or irregularly in members of an affected 
family. 

Rossle says normal and pathological characters, but not diseases, are 
inherited. The germ cell is not infected with the cause of syphilis, but the 
fetus is influenced by having been formed in persons affected with syphilis 
and so modified that their ovum or spermatozoon fails of normal progress 
in embryonic development. The fetus may of course have syphilis 
acquired in utero via the placenta. The influence of maternal conditions 
is naturally the greater. Abnormalities in offspring of consanguineous 
parents are now explained as a summation of the natural tendencies of 
both parents. 

Hereditary Congenital Pathological Conditions. — Such conditions as 
hemophilia and color-blindness, familial nervous disorders, joint mal- 
formations, and skin anomalies are placed in this group. 

Pathological Conditions of Later Life Depending Upon Heredity. — 
This heading refers to the related subjects of predisposition and diathetic 
reversionor inheritance. Such diseases as gout, diabetes, and insanity are 
covered. Here one may place the undeveloped physique and constitu- 
tional lack of resistance to tuberculosis in the children of affected parents. 

A number of theories have been constructed to explain the mechan- 
ism of heredity. Darwin, in his hypothesis of pangenesis, suggested that 
minute particles are given off from all of the cells of the body; these are 
collected in the reproductive cells, which, in consequence, represent all 
of the bodily characteristics, hereditary and acquired. Weismann 
denies the transmissibility of acquired characteristics, and holds that 
in the process of reproduction a certain amount of "germ-plasm" passes 
from the parent cell into the offspring, where it remains, and is in 
turn passed on to succeeding generations, thus perpetuating ancestral 
characteristics. 

Another theory of heredity is called epigenesis, or that process through 
which an ovum goes in its maturation process when it develops under 
its appropriate biological environment. This theory does not accept the 
statement that in the ovum there is a preformed molecule that will 
eventually develop into a particular part, as is the case with the two 
previous theories. It assumes that the development of the individual 
occurs in harmony with that of the race. 



THE ETIOLOGY OF DISEASE 



23 



However, it has been shown that with the earliest stages of a de- 
veloping ovum certain differentiations occur which apparently stand as 
forerunners of certain bodily parts, and the development depends upon 
the preserved integrity of these primary divisions of the ovum. It has 
also been shown that an embryo when dividing shows distinct polarity. 
These facts militated against the epigenetic theory and gave rise to the 
mosaic theory, which assumes the control of bodily parts by definite 
molecules or blastula segments. 

It must not be forgotten in the study of heredity that, while the 
atomical changes are measures of evolution and heredity, the chemistry 
of the biological mass must be similarly affected. If, as has been main- 
tained by some authors, the disproportion between the surface tension 
in nucleus and protoplasm combined with alterations in the chemical 
constituents as a result of this, be the cause of cell growth, then any 
disturbance of the cell tension or chemistry will be felt by new cells the 
product of the division. If the parent cell has established for itself a 
definite chemical cycle, its progeny will continue this cycle. This is 
another application of Baumgarten's anlage, and shows the close associa- 
tion of heredity and predisposition. 

The theories and experiments upon heredity have given rise to certain 
generalizations and laws which are now explained. 

Racial inheritance expresses itself in functional or anatomical varia- 
tion. Races are peculiar in resistance to parasitic diseases and in the 
maintenance of certain physical characters. 

Familial inheritance is similar in principle to the former, and is well 
illustrated in hemophilia (q. v.). 

Blended and Particulate Inheritance. — The former means a har- 
monious admixture of characters of the parent, while the latter means 
the domination of some particular character. Mendel's law: The 
observations of Gregor Mendel upon self -fertilizing plants showed the 
transmission of character to follow a very definite law. When two or- 
ganisms, one so-called dominant, the other recessive, reproduce, the off- 
spring contains a mixture of the two, although dominant characters 
show more clearly. The second generation shows one pure dominant, 
two admixtures of dominant and recessive, and one recessive. Self- 
fertilization will produce always dominant from dominant and recessive 
from recessive. Offspring of admixtures will produce, as in the second 
generation, a dominant which will continue a dominant, a recessive 
following this type in its progeny, and mixtures of dominant and recessive 
and recessive and dominant. These last two will then follow the same 
course by producing two pure and two mixed progenies. This law 
has been worked out with many plants and some small animals. It has 
not been directly applied to man, but it is obvious that the domination of 
characters must have influence upon offspring. Galton's law claims that 
the parents each supply a quarter of the influence to the offspring; the 
four grandparents, each a sixteenth, and so backward to the completion 
of the unit. 

For the mosaic inheritance and atavism see above. 
Reversionary inheritance is atavistic reversion to a lower condition 
or incomplete type. 



24 



A TEXT-BOOK OF PATHOLOGY 



Diathetic inheritance is a transmitted tendency in a particular direc- 
tion. (See Pathological Disposition and Predisposition.) 

Cumulative inheritance is a summation or exaggeration of charac- 
ters from both parents. 

Mutation is the assumption of character not peculiar to the given 
species. 

Determining Causes. — Among the immediate or determining causes 
of disease are those which originate outside the body and those which 
are generated within the body. Among the former are included trau- 
matism, heat, cold, and other physical agents, poisons, and living organ- 
isms, including bacteria and various animal parasites. The causes of 
disease originating within the body itself are less definitely known, but 
it has been found in chemical studies that various products of normal 
metabolism when accumulated in abnormal quantity, or products of 
disturbed metabolism, may occasion local or widespread disease of 
various sorts. This self-poisoning is designated auto-intoxication. 

The term " auto-intoxication " is frequently applied to poisoning by 
products of intestinal putrefaction. This application of the term is not, 
strictly speaking, correct. The same poisons might have been produced 
by putrefaction of food outside the body, when the use of the name auto- 
intoxication would be manifestly absurd. If poisons are produced by 
imperfect digestion, and these affect the organism, the condition could 
properly be termed auto-intoxication. 

TRAUMATISM 

Traumatism, or mechanical injury, may be of various sorts, gradual 
or sudden, small or large; and the effects are dependent upon the form 
and severity of the injury. Pressure brought to bear upon a part leads 
to disturbances of the circulation and more or less direct injury of the 
cellular elements. When the pressure is gradual, true atrophy of the 
part may occur, as in the case of the atrophic liver resulting from lacing. 
When the pressure is greater and the circulation is completely arrested, 
more destructive change may result, such as necrosis or gangrene. This 
is seen in the necrotic atrophy of bone resulting from the pressure of 
aneurysms, or the gangrene of extremities resulting from ligation. 
Wounds. — Frequently, inflammatory reaction occurs in the surrounding 
tissues when traumatic injuries have been sustained. This is illustrated 
in all forms of wounds, and it is through the inflammation and sub- 
sequent regeneration of tissue that the areas of destruction are restored. 
In cases of injury by fine particles, as in powder-marks of the skin, or 
the surface injuries sustained by miners and metal-workers, or in indi- 
viduals inhaling sharp particles like coal-dust, marble-dust, or steel-fil- 
ings, small injuries of the tissues result. The foreign bodies may be 
subsequently discharged, leaving a focus of inflammation, or the 
inflammation may surround the particle embedded in the tissue, and 
encapsulation by fibrous-tissue formation may occur. Large injuries in 
which the tissues are contused or broken may lead to extensive inflam- 
mation, in part the result of the direct injury to the tissues and in part 
the result of injury of the blood-vessels. 



THE ETIOLOGY OF DISEASE 



25 



An injured surface presents a locus minoris resistentice which offers 
an entrance to organisms already in the locality or to those that might 
be actually driven into the tissue or blood-stream by the damaging 
force. 

Gross traumatism of the body as a whole, as in falls, crushing injuries, 
etc., causes various disturbances according to the part mainly involved. 
Rupture of the viscera, as the lungs, heart, liver, spleen, stomach, or 
intestines, may occur. When the head is violently struck, unconscious- 
ness is common as a consequence of either disseminated punctiform 
hemorrhages, large focal hemorrhages, or obscure and possibly only 
functional disturbances. Commotio cerebri, the condition occurring in 
such cases, may ,be fugacious or may lead to permanent disorder de- 
pendent upon organic changes in the brain. Spinal symptoms, met with 
after railway injuries and like accidents, may be due to hemorrhage and 
secondary morbid processes in the cord, or may be due to the uncertain 
pathological conditions constituting hysteria. 

The relation of a single trauma to tumors is not entirely clear. It 
seems that a new growth has been observed at a point where an injury 
has been sustained. Repeated minor traumata or continued irritation 
seem to precede some epithelial growths. The most notable example 
is the epithelioma of the lip of clay-pipe smokers. The injury in these 
cases can hardly be a determining cause. The occurrence of a tumor at a 
site of injury is not inconsistent with any of the principal theories of 
cancer origin. 

Epithelial cysts may arise at points of injury by the displacement of 
epithelial cells to a position below the surface. These are not true neo- 
plasms. 

Shock. — It is perhaps well to consider at this point a condition 
frequently a sequel of severe or prolonged traumatism, namely shock, 
but it must be emphatically stated at once that the group of signs under 
this name arises at times without gross physical injury (nervous or 
anesthetic shock). The picture of shock is that of a person with rapid 
shallow respiration, frequent feeble pulse, dilated pupils, moist pallid or 
cyanotic skin, anemic mucous membranes, falling temperature, apathy 
deepening in severe cases into unconsciousness. The slowness of the 
reflexes is noteworthy, for while the patient may be conscious, it requires 
strong or repeated urging to elicit replies and deep stimuli to awaken 
reflex response. The only things suffered by the patient are chilliness 
and numbness ; otherwise he is indifferent to his surroundings. Sphincter 
tone is maintained. 

The causes of this shock may be cited in about the order of their 
importance and urgency as follows: Surgical operations, traumatism, 
hemorrhage, nervous shocks, anesthesia, and localized injuries. Surgical 
shock is that due to prolonged or vigorous handling of internal structures, 
notably but not solely the abdominal viscera and as the results are the 
same and operations are usually conducted under ether, it may be dif- 
ficult at times to decide the prime cause in any given case since the 
prolonged administration of ether alone can produce shock; nitrous 
oxide and oxygen anesthesia is practically not followed by shock. 
In cases of blows, as for example on the testes or abdomen, the 



26 A TEXT-BOOK OF PATHOLOGY 

effect is evidenced in immediate or delayed shock depending usually 
upon the intensity of the force and the size of the area struck. Hemor- 
rhage especially when more than two per cent, of the body weight is 
lost, leads to shoek but internal hemorrhgea may have the same effect. 
In certain neurotic individuals, a minor injury may precipitate shock or 
it may occur in such persons without trauma as the result of anticipation 
or in the fear of danger or after seeing unpleasant sights, such as occurred 
in the late war (shell shock); in the last cases shock is delayed, slow in 
development and has a distinct neuropsychiatric element. A localized 
condition of shock may arise after injuries to the spinal column particu- 
larly those that sever or transversely compress the cord, in which case 
only the parts supplied by the nerve routes below the line of injury present 
the proper signs. 

Despite the varied conditions under which shock may arise, the mani- 
festations are strongly similar, suggesting that all the causes must have 
one particular action but what this may be is as yet unknown, although 
enough information is on hand concerning the abnormal physiology to 
make clear, at least in part, what is transpiring and to indicate some 
fairly useful remedial agencies. Most of the symptoms and signs of 
shock may be stated categorically to depend upon one condition, namely, 
lowered blood pressure, which has as its sequels the rapid pulse and 
respiration, leaking skin with its consequent greater radiation of heat, and 
decreased reflexes and cerebration because of anemia. The marked and 
continued failing of blood pressure is due in the first place to a decreased 
amount of blood being pumped by the heart which in turn is due to a fail- 
ure of return of sufficient venous blood. The veins and capillaries are at 
first in a state of contraction but shortly the latter become engorged with 
blood. This stagnation is held by. some to be the cause of low pressure 
since the heart cannot get enough bulk of fluid to pump against. Others 
are of the opinion that the primary brain anemia induced by the agent 
causing the shock reduces the activity of the vaso-motor and certain 
sensory centers and that a vicious circle is established because they 
are unable to get more blood on account of vaso-motor depression. It 
has been asserted that degenerative changes occurring in the central 
ganglion cells are the cause of shock, but these are not peculiar to shock 
and could be coincidences or the result quite as well as the cause. 

The reason for the stagnation of blood in capillaries is not yet ade- 
quately explained; to pursue its discussion would lead to speculation 
but it will suffice here to state a few isolated facts. The capillaries 
actually contain more corpuscles and less fluid (increased viscosity) 
than normally, the latter draining into adjacent tissues. Because of 
slow circulation of blood, oxidative processes are slow, and acidosis 
arises, a condition further affecting cardiac muscular power. In addi- 
tion there is a lowered carbon dioxide combining power of the blood, 
due it is asserted, to rapid respiration, the result of excessive sensory 
stimulation of the respiratory center. The loss of heat is continuous, 
while the above conditions exist and assists in intensifying their effects. 
It is asserted that, when the primary causes of shock does damage 
to tissue, there are certain substances, probably degradation products of 
protein, elaborated and absorbed, which have a local and central depressing 



THE ETIOLOGY OF DISEASE 



27 



effect upon vasomotor apparatus. This may be effective in some cases 
of delayed shock but it is manifestly not a factor in all varieties. 

The syndrome appearing after the injection of certain sera or that 
occurring occasionally during severe intestinal or infectious intoxications 
is akin to the above but, having been explained on a more strictly bio- 
chemical and immunological basis, will be discussed under anaphylactic 
shock (q. v.) 

PHYSICAL CONDITIONS 

Heat. — High temperatures produce local or general results ac- 
cording to the mode of application and degree of heat. 

Local excess of heat produces various lesions. Moderate excess leads 
to relaxation of the walls of the blood-vessels; with increasing grades of 
temperature there is, in addition, necrotic change in the cells of the part, 
and exudation of serum causes vesicle formation. Still higher grades 
of temperature produce immediate destruction, perhaps with charring, 
of large or small areas, while the surrounding tissues suffer from reactive 
inflammation and hyperemia. Extensive burns involving one-third 
or more of the surface of the body frequently cause death. In these 
cases it is likely that poisonous products are formed, either directl}' 
through tissue and blood destruction, or indirectly through disturb- 
ances of the functions of the skin or internal organs. The immediate 
manner of death is often in the form of shock; when the termination is 
delayed, various vascular, hemic, and tissue disturbances may occur. 
Intravascular coagulation is not unusual, and is not improbably the 
result of the liberation into the blood of tissue elements set free in the 
areas of local destruction, or to substances produced by direct destruction 
of the blood. The same substances may account for the existence of 
fever (ferment intoxication). The intravascular coagulation caused 
in this or other ways may induce venous stasis and localized hemorrhages. 
Focal necrosis or degeneration of the tissues of various organs, such as 
the liver, kidneys, or the mucous and serous membranes, may be due to 
thrombotic occlusion of vessels, or to the influence of circulating poisons 
without thrombosis, or to both. It seems probable that the cause of all 
these physical changes is a necrotizing toxin arising in the burned skin. 
(Some manifestations of this condition resemble anaphylaxis.) Marked 
changes are found in the lymphatic glands as well as in the Malpighian 
bodies of the spleen and in the bone-marrow. These changes present 
themselves as areas of leukocytic degeneration containing actively 
phagocytic endothelial cells and surrounded by a zone of lymphocytic 
invasion. The lesions are not unlike those produced by abrin, ricin, 
and bacterial toxins. Duodenal ulcer is often referred to as an occasional 
result of extensive burns. The blood itself may present evidence of 
disease in the form of degenerations of the corpuscles, in the reduction 
of their number, and of the amount of coloring-matter, while regenerative 
changes frequently present themselves some time later (nucleated red 
corpuscles). Changes in the urine may occur in cases of extensive burns, 
in consequence of the tissue destruction (hemoglobinuria, albumosuria). 

Exposure to general high temperature varies in its effects according 
%o the manner of exposure (dry air, steam, etc). An animal exposed 



28 



A TEXT-BOOK OF PATHOLOGY 



to a constant temperature somewhat above the usual surrounding tem- 
perature presents a slight increase of its body heat, which is compen- 
sated for by increase in the respirations and pulse-rate. Much higher 
temperatures may cause death by coagulation of the tissue proteins,, 
notably in the muscular structure of the heart or the respiratory muscles. 
Before this extreme is reached, however, it may be found that the con- 
sumption of the tissues of the body is greatly in excess, though the re- 
spiratory quotient is altered in favor of the amount of oxygen consumed. 
Continuous exposure to excessive heat frequently causes peculiar dis- 
turbances in man, known as heat-stroke, sunstroke or insolation and 
heat exhaustion. In these conditions hyperemia and edema, or even 
inflammation of the meninges, may occur. These lesions are some- 
times supposed to be the result of the direct effect of the heat; but there is 
reason to believe that they may be occasioned by poisonous substances 
produced within the body by metabolism, disturbed as a result of the 
heat, which toxins are thought to have a depressing effect upon the heart- 
muscle ; cardiac power is surely not up to normal. The blood is quite con- 
centrated probably because of the excessive dissipation of moisture. One 
evidence of the effect on the blood of continued elevation of temperature 
is the appearance in the red blood-corpuscles of basophilic granules — 
granular degeneration of Grawitz. (See chapter on Blood.) Exposure 
to high temperatures for long periods, such as steamship stokers are 
subjected to, produces cramps in the muscles, chiefly of the extremities. 
The excitability of the muscles is greatly increased. 

The autopsy upon a death from heat-stroke shows an early rigor 
mortis and decomposition, general passive congestion due to weak heart 
action, a fluid condition of the blood, and sometimes hemorrhages into 
the medulla. 

A portion of the body, as an arm or a leg, may be exposed for a 
limited time to excessive temperatures (300° to 400° F.) in dry air 
without injury. The general temperature is slightly elevated, but 
metabolism is practically unaffected. 

The effects of general or local heat are much increased when the 
organism as a whole or in the part involved is below par. A paralyzed: 
limb is burned or scalded at comparatively low temperatures. 

Cold. — Exposure to extreme degrees of cold may cause results- 
quite similar to those produced by heat. Exposure of the skin to lique- 
fied air, solidified mercury, or other substances at excessively low tem- 
peratures produces vesiculation and necrosis of the tissues like those 
produced in burns. 

Exposure of the body to greatly reduced but bearable temperatures 
of the surrounding atmosphere causes vascular disturbances followed 
by necrosis of the tissues and inflammatory changes. The parts so 
affected are the extremities or projections of the body, like the toes- 
and fingers, nose and ears. The primary result of cold is vascular 
constriction and local anemia, factors upon which most students of the 
subject have laid great weight. These serve the purpose of preserving 
the body heat by preventing heat radiation; later the blood-vessels are 
paralyzed and extreme hyperemia results. Then cellular exudation and 
necrosis may occur. These changes are well seen in the condition 



THE ETIOLOGY OF DISEASE 



29 



termed chilblain while still greater exposure may lead to distinct necrosis 
or gangrene of an extremity. In prolonged exposure to cold there are a 
gradual reduction in the activity of the various organs and a gradual 
obtunding of the sensibility until the patient becomes comatose. The 
retention of excrementitious products of metabolism, or the formation of 
products of abnormal metabolism, may be important in causing this 
condition. There is a reduction of hemolgobin and red cells, increase of 
C0 2 excretion, and disappearance of glycogen. Autopsy shows edema of 
lungs, with or without congestion, and transudates into serous cavities. 

Freezing of the body as a whole leads to death it is believed, not by 
damage to heart or respiration especially, but by depression of all meta- 
bolic processes and the inability of the heat center, trained to work only 
against a certain variation, to accommodate itself to the excess radiation. 
The outcome of freezing depends upon its duration, and recovery seems 
possible in certain cases. After death the only changes found are 
peripheral ischemia and internal congestion, at times with hemorrhage. 

Exposure to cold plays an important part as a clinical cause of dis- 
ease. Various forms of pharyngitis and coryza or bronchitis so fre- 
quently follow such exposure that the term "cold" is generally used. 
Other conditions, like rheumatism, pleurisy, pneumonia, and the like, 
bear a similar relation. It is now recognized that in most of these 
cases cold is merely a predisposing cause, the immediate cause being 
in many, if not all, cases specific micro-organisms. The mode of action 
of the exposure is uncertain; probably it causes a reduction in the resist- 
ing powers of the organism and thus favors the activity of bacteria. 
The hyperemia following exposure to cold is associated with lowered 
alkalinity of the blood, thus favoring bacterial increase. The phago- 
cytic action of leukocytes is reduced by exposure to cold, and it is 
said that complement and antibody do not combine so readily with 
antigen. This is true in vitro. 

Increased Atmospheric Pressure. — Exposure to extreme pressure 
of several atmospheres may occur among deep-sea divers or in men 
working in caissons used in bridge building. Little disturbance may 
be caused at first or for a long time; but on return of the workmen to 
the usual atmospheric conditions symptoms make their appearance 
(caisson disease). Among these symptoms are bleeding from the nasal 
or other mucous membranes, great depression, delirium, and paralytic 
conditions. Congestion, degenerations, and vacuolations in the spinal 
cord have been discovered in some cases. 

The cause of the lesions is a hypertension of nitrogen within tissues. 
Tissues hold much more nitrogen than the blood, so that this gas is held 
in them because the blood becomes saturated each time it passes through 
the lungs. When the person returns to normal atmospheric pressure 
the tissues give up to the blood their retained gas. The blood and 
lungs can excrete but slowly, so that bubbles of nitrogen under release 
of pressure appear in tissues and vessels.' These bubbles are the cause 
of hemorrhages, fissures, and gas embolism. 

Decreased Atmospheric Pressure. — Effects of decreased press- 
ure are seen in inhabitants of high altitudes and in persons ascending 
in balloons. Marked excitement of the vascular system, increased 



30 



A TEXT-BOOK OF PATHOLOGY 



respiratory effort, hemorrhages, somnolence, weakness, vomiting, and 
similar symptoms are observed ; in less marked cases a general excitement 
of the nervous system, sleeplessness, occur. The low partial pressure of 
oxygen at high altitudes has in all probability something to do with 
the condition, combined with which is, according to some physiologists, 
an inability of pulmonary tissue to adjust itself rapidly to use the oxygen 
at this pressure. Some investigators consider the unusual sensory 
stimuli experienced at high altitudes to have an effect upon respiratory 
and vascular centers. A mild acidosis exists. Investigations show that 
the blood contains greatly increased numbers of red corpuscles in a given 
volume, and the percentage of hemoglobin is correspondingly increased. 
This is probably due, to some extent, to disturbance in the distribution of 
the corpuscles with stagnation in the peripheral vessels (see Diseases of the 
Blood). 

Insufficiency of Respiratory Air. — A certain amount of air is 
necessary for the continuance of health or life. Insufficiency may be 
due to diseases which obstruct the air-passages or affect the pulmonary 
tissue itself, and to foreign bodies (solid bodies, water in drowning) 
within the air-passages. Changes in the atmosphere or gases taken into 
the lung may cause insufficiency in the supply of oxygen, notably in 
CO-poisoning ,in which the foreign gas enters into firm combination with 
the hemoglobin of the blood and thus excludes oxygen. 

Insufficiency of air in the sense of improper or vitiated air is usually 
to be attributed to a failure of movement or replacement, the effect of 
which will be an interference with heat radiation, consequently there 
will be metabolic disturbances and early fatigue. In the most satis- 
factory air supply, temperature must also permit radiation and there is 
a roughly inverse proportion between desirable rate of movement and 
temperature. 

Moderate decrease of the supply of air causes labored and rapid 
breathing, more or less cyanosis, depression, and stupor. This con- 
dition is termed asphyxia. Complete lack of air causes increase of these 
symptoms and death by suffocation. 

The appearance of the body after asphyxia or suffocation is most 
characteristic in the face which is swollen, cyanotic or blotchy; in 
strangulation it is much enlarged and the eyes and tongue may protrude. 
The lungs are deeply congested while the air passages including the mouth 
and nose, may contain bloody froth. Hemorrhages have been seen in 
the organs and cavities. The heart is dilated with dark fluid blood 
the right side being especially enlarged. After recent drowning the con- 
ditions are much the same except for such conditions as may arise by 
water and soil getting into the lungs and stomach; prolonged stay in 
water is usually accompanied by much decomposition. 

The respiratory rhythm is maintained by the regular stimulation 
of the respiratory center by the appropriate mixture of carbon dioxid 
and oxygen in the circulating fluids. If, by repeated deep inspiration, 
the amount of C0 2 in the blood decreases (called acapnia), there is no 
stimulation of the respiratory center and a condition of true apnea 
ensues. This view of apnea is maintained by some, while others claim 
that apena may be induced after section of the vagus, and that, therefore, 



THE ETIOLOGY OF DISEASE 



31 



the gases in the blood are always responsible for apnea. This term should 
be used for the interruption of respiration due to the above causes, 
and not to cessation by mechanical or voluntary causes. 

Long-continued insufficiency of oxygen may directly or indirectly occasion de- 
generative diseases of the tissue. It has often been asserted that anemia causes many 
of its symptoms and results because the blood is incapable of carrying sufficient oxygen 
in its reduced state. As a matter of fact, however, physiological experiments have 
demonstrated that the respiratory exchange (inhalation of oxygen and exhalation of 
carbonic acid gas) is but little affected and is as frequently increased as decreased. 

Electrical Influences. — The effects of powerful electrical currents 
and discharges on the tissues resemble those produced by burns. Locally, 
a dry, crisp, excavated lesion is produced. Later, hyperemia and ap- 
pearances resembling moist gangrene develop. The underlying muscles 
are more or less paretic. Changes in the blood-vessels and a fluid state 
of the blood, extending to some distance from the local lesion, have 
been observed. Very powerful and fatal discharges in some cases 
produce hemorrhages in the floor of the fourth ventricle and petechiae in 
the serous membranes and elsewhere. There are degenerations of nerve- 
cells, particularly in ganglia. Death seems to be caused by powerful 
inhibition of the heart. Lightning stroke leaves branching linear burns. 
Less powerful discharges, such as dynamo workers receive, cause sting- 
ing sensations in the absence of burns. If prolonged, there is loss of 
consciousess, depending for its depth upon the amount of and duration 
of the current. There is no definite amount that the body will always 
endure. 

Effects of Rontgen and Similar Rays 

The physical forces here considered are from the portion of the spec- 
trum beyond the violet-x-rays, Radium rays and ultraviolet rays and are 
not visible to the eye. The action of the first two is similar and is ex- 
pressed in the skin at first by reddening and heat which are followed, if the 
radiation continue, by blistering, loss of hair, and pigmentation, which may 
go over into a sluggish ulcer. When ulceration has not been extensive a 
chronic dermatitis like xeroderma pigmentosum remains, often with per- 
sistent painful cracks. The epithelium (glandular cells are somewhat 
resistant) shows one of two conditions; it is either swollen and vacuolated 
or there is marked hyperkeratosis. With this there is a tendency to 
grow downward and epithelioma only too often results. The subjacent 
tissue is poor in vessels because the rays have the power to cause endothe- 
lial degeneration and thrombosis in arteries and capillaries. The rays 
have the effect of destroying blood forming cells in the bone marrow, the 
effect seeming to be upon the nuclei, and less, if at all, upon the cyto- 
plasm; this cell destruction is also seen in lymphatic tissues. Radiation 
destroys spermatozoal centers without producing physical impotence and 
it is probable that ova are likewise killed. There seems to be no special 
difference in the action of rays upon normal and tumor cells so that 
radiation of tumors should only be given when ample protection of 
healthy tissues is possible; superficial growths hold out more promise than 
deep ones. X-Ray affects metabolism by increasing uric acid nitrogen 
and phosphorus (from nuclei) excretion and by splitting lecithin. 



32 



A TEXT-BOOK OF PATHOLOGY 



The ultraviolet rays of the spectrum are responsible for burning, 
tanning and freckling and possibly for the color of the dark skinned in- 
habitants of tropics. Prolonged exposure of blond persons leads to a 
mild irritative dermatitis, or if quite prolonged and repeated, to a chronic 
indurative condition with hyperkeratosis and ulceration. 

POISONS 

Definition. — The term "poison" may be applied to substances which 
when introduced in relatively small amounts into the living organism 
disturb its structure or functional activity. 

The Action of Poisons in General.- — Gaseous poisons act primarily 
upon the respiratory mucous membranes with which they come in 
contact, or after absorption into the blood disorganize this fluid or lead 
to disturbances of the nervous system. Liquid poisons are generally 
absorbed through the gastro-intestinal mucous membrane, but may be 
received directly into the tissues by injection under the skin; they 
are rarely absorbed through the skin. Solid poisons must in all cases 
first be dissolved, and are then absorbed like the liquid poisons. They 
may by their strong attraction for water absorb the latter directly 
from the tissues, and by this process alone may bring about important 
changes. 

The lesions due to a poison may be entirely local, as in the case 
of certain corrosives or caustics; in other cases the point of entrance is 
unaffected, the pathological manifestations being entirely due to the 
changes in different parts of the body or to nervous disturbances, result- 
ing from the circulation of the poison in the blood. Some poisons act 
immediately in destroying cells (caustics), while others must combine 
with them before the toxic effect is manifest; in other words, there is a 
latent period. 

The fate of poisons after ingestion is very different in different 
cases. Some poisons circulate with the blood and are eliminated un- 
changed. Others may suffer chemical change within the stomach or 
other cavities of the body before absorption, and may be either com- 
pletely neutralized, or may be converted into forms which are sub- 
sequently slowly absorbed. After absorption into the blood other chemical 
reactions may occur, and the poison may be more or less neutralized, 
the system then suffering either from the resulting compounds or from 
the changed condition of the blood. Active destruction of the poison 
may occur in the blood or in the various organs, especially the liver. 
In these processes, however, the glandular organs may suffer seriously, 
various forms of degeneration or necrosis resulting. Certain poisons, 
like the toxins, enter into chemical combination with cells of the body 
and remain fixed in this way. (For further details see Immunity) 

The defense of the body against poisons lies in substances natural to 
it, and probably not increased in response to intoxication. This does not 
apply to the bacterial toxins in bacterial infection, but if injected in the 
absence of general infection some of the bacterial toxins may be de- 
toxicated as are inorganic or higher vegetable poisons. Among the 
defensive bodies are the blood, bile salts and acids, sulphuric acid as 
such or as sulphates, and the fatty acids. The processes at work are 



THE ETIOLOGY OF DISEASE 



33 



rapid elimination, oxidation, reduction, and hydrolysis. Poisons may 
be changed in form by precipitation or altered by combination with 
body proteins. 

The effect of poisons depends upon the dose as well as upon the 
nature of the substance, and also upon the individual. The repeated 
ingestion of certain poisons, such as arsenic or opium, may generate a 
considerable degree of immunity or tolerance (mithridatization) . Simi- 
lar immunity may be a natural characteristic of a given individual or 
of classes or species. This, however, cannot be called an immunity in the 
ordinary sense of the word and, while the cause of the resistance is far 
from clear, the nearest one can come to explanation now, is that the body 
learns elimination and exercises this function more thoroughly; the power 
of dehydration, reduction and the like is apparently increased in the 
resistant individual. Susceptibility to the action of poisons is further 
influenced by age and constitutional vigor. Children bear certain 
poisons better, comparatively speaking, than adults, while the reverse 
is true of other substances. Sometimes there are idiosyncrasies which 
lead to peculiar results not observed in the average individual. In 
consequence of this, substances ordinarily not toxic may be extremely 
injurious to certain persons. (See Allergie.) 

Sometimes poisons are comparatively innocuous when administered 
in one way, though powerfully toxic to the same animal when other- 
wise introduced. Thus in dogs intravenous injection of atropin is very 
slightly injurious, but injection of minute doses into the spinal cord 
-causes rapid poisoning. Some experiments would indicate that the 
leukocytes are capable of fixing inorganic poisons and thus acting as 
defensive agencies. 

In general, the action of poisons ma}^ be immediate destruction, 
stimulation ,to exhaustion and disintegration, or inhibition gradually 
to cessation of function. There are poisons with special predilection, 
e. g., strychnin for the nervous system; phosphorus for bone; snake- 
venom for blood, nervous tissue, and spleen. 

Elimination. — -The excretion of poisons may take place through 
the kidneys, lungs, the mucous membrane of the gastro-intestinal 
tract, the mammary glands, or the skin. In some i nstances a poison is 
eliminated without change in the excreta; in other cases it suffers com- 
plete change, and is not present at all in the excretions. The rate of 
elimination varies greatly, and is more or less dependent upon condi- 
tions of the system. Some poisons, as phosphorus and mercury, may 
be stored up within the body for a considerable period, subsequently 
suffering slow elimination. 

Classification. — The number of substances which may act as poisons 
is very great, and the manifestations are of very different sorts. Classi- 
fication of poisons is, therefore, difficult and not entirely satisfactory. 
We may crudely distinguish between gaseous, liquid, and solid poisons; 
between animal and vegetable; organic and inorganic; but these classi- 
fications have no scientific value. 

From the point of view of the action of the poisons we may dis- 
tinguish corrosive poisons, or those which have a local action; organic or 
parenchyma poisons, or those which act less strongly at the point of 

3 



34 A TEXT-BOOK OF PATHOLOGY 

application than upon the various organs to which they are conveyed 
through the blood; blood-poisons, or those which exercise their effects 
primarily upon the blood; and the nerve-poisons, or those which disturb 
the functional activity of the nervous system without producing defi- 
nitely peculiar lesions. 

Corrosive Poisons; Escharotics; Caustics. — Under this heading 
are included various acids, alkalies, and mineral poisons, such as sul- 
phuric, nitric, oxalic, carbolic, and hydrofluoric acids, caustic potash 
or soda and ammonium, and gases like chlorin and bromin. Nitrate of 
silver, bichlorid of mercury, sulphate of copper, and other inorganic 
compounds have a similar action, and certain organic bodies, such as 
cantharidin and croton oil, belong to the same class. 

All these poisons exercise a destructive effect upon t)ie cells with 
which they come in contact, partly by abstraction of water and partly 
as a result of a coagulating power or similar action. The acids and 
mineral caustics usually produce dry and more or less discolored areas 
of necrosis; the caustic alkalies cause a sort of gelatinous change or a 
saponification of the tissue. The degree of injury depends upon the 
poison and the amount in contact with the tissues. There may be only 
a superficial injury of the outer layer of epithelial cells, or extensive 
destruction. Reactive inflammation is almost always present, and 
often, especially in the mucous membranes, the inflammatory reaction 
is extensive, though the corrosive action of the poison is limited in depth 
and extent. The affected part may present slight areas of necrosis with 
reactive hyperemia and inflammation beneath and around them, or 
deep eschars, vesicles, or large bullae. In the process of healing, extensive 
scars may form, and these may be serious in their effects, as in the case 
of strictures of the esophagus. 

Organic Poisons; Parenchyma Poisons. — This large group includes 
many metallic compounds that have a local corrosive or escharotic 
effect, but which may in smaller dose gain entrance to the blood and 
cause extensive organic lesions. It also includes poisons of vegetable 
origin and products of bacterial growth. In general, these poisons have 
a similar action. The kidneys and the mucous membrane of the intes- 
tines are especially active in their elimination and suffer most seriously. 
Degenerations of the epithelial cells of various sorts are met with, 
such as nuclear degenerations, coagulation necrosis, fatty degeneration, 
and even calcification. The changes may be diffuse or may occur in 
small foci. In the latter case small areas of granular appearance, 
having a lighter color than the surrounding tissues, are seen; and on 
staining the cells are found to color poorly or not at all, the nuclei often 
showing this change first. Nuclear degenerations (fragmentation, 
hyperchromatosis, etc.) are observed, and in some instances marked 
fatty degeneration of the cells occurs. Around the foci of degeneration 
there is more or less cellular infiltration (polymorphonuclear cells) 
and to a less degree the degenerated area itself is infiltrated. In cases 
in which diffuse change occurs there is equally diffuse round-cell infil- 
tration. After the acute process has subsided, hyperplasia of the con- 
nective tissues may occur and the affected part becomes more or less 



THE ETIOLOGY OF DISEASE 



35 



sclerotic or indurated. Regeneration of the parenchyma cells is less 
apt to occur. 

Some of the more important of the poisons of the group may now 
be separately considered. 

Phosphorus is a poison of considerable activity in the yellow form; 
the red variety is inert. Workmen in match factories are the most 
frequent victims of this form of intoxication, but occasionally accidental 
poisoning by swallowing occurs. In the latter the manifestations are 
acute. The pathological changes are catarrhal inflammation of the 
gastro-intestinal mucous membrane and more or less widespread fatty 
degeneration of various tissues and organs. The liver suffers most 
severely, being enlarged, light yellow or reddish in color, and friable or 
doughy. Microscopically, the liver-cells are found extensively de- 
generated (fatty). Similar but less marked fatty degeneration is 
found in the renal tubules, gastro-intestinal epithelia and heart-muscle, 
and in the intima of the blood-vessels. Extensive jaundice is frequent 
and. numerous hemorrhages may occur. In the more chronic poisoning 
of match-makers the poison enters through the mouth and respiratory 
passages, being inspired as dust. Chronic catarrhal inflammation of the 
respiratory tract may occur and a peculiar form of necrosis of the 
bones (see Bones) is met with. 

Arsenic is poisonous in certain forms (white arsenic, arsenous 
acid) and inert in other forms (the sulphids). Acute poisoning occurs 
when toxic forms are swallowed in large doses; the chronic forms, of 
poisoning result from gradual ingestion or the inhalation of dust con- 
taining arsenic. Cases of the latter sort occur when wall-paper, hang- 
ings, and the like, colored with arsenic pigments, are used. The lesions 
in acute arsenic-poisoning resemble those produced by phosphorus 
although in some acute cases the arterial changes, especially in the kidney, 
are noteworthy, leading usually to minute hemorrhage and extravasation. 
The gastro-intestinal inflammation is, however, more severe, while the 
fatty degeneration of the organs is less marked. In chronic arsenic- 
poisoning changes in the peripheral nerves (degeneration and inflam- 
mation) are most important. It is likely that focal or diffuse myelitis 
may likewise be caused by this poison. Chronic inflammations of the 
gastro-intestinal or respiratory mucous membranes are met with in 
some cases. Inflammatory lesions and pigmentation of the skin may 
occur. 

Lead. — Among the compounds leading to acute or subacute poison- 
ing the chromate, the acetates, the carbonate, and oxid are most im- 
portant. Chronic poisoning occurs in workmen in paint manufactories 
and among type-setters and painters, and in persons drinking certain 
waters that have been conducted through lead pipes. Less rarely the 
use of cosmetics, dyestuffs, etc., containing lead causes chronic poison- 
ing. In the acute forms of lead-poisoning moderate gastro-enteritis 
occurs. In the chronic form changes in the nervous system are most 
important. Peripheral neuritis is the most frequent lesion, but changes 
in the large ganglionic cells of the gray matter of the cord, minute hem- 
orrhages and fine focal necroses in the brain substance, have some- 
times, been found. Diffuse sclerosis of the blood-vessels, noticeable in 



36 



A TEXT-BOOK OF PATHOLOGY 



large ones but rather characteristically occurring in small ones, hav- 
ing a decided influence in the production of an interstitial nephritis of 
a disfigurating type, are quite common. Involvement of bursae, tendons 
and ligaments in a manner suggesting the lesions of gout may be present. 
Atrophy and fatty degeneration of the muscle-fibers are less important 
results. A blue line on the gums at the junction with the teeth (due to 
deposit of sulphid of lead) is a lesion of clinical importance. A constant 
and diagnostically suggestive change is found in a peculiar degeneration 
(basic degeneration) of the erythroctyes. (See chapter on Blood.) 
Chronic plumbism in the male leads to a reduced weight and early 
mortality of the offspring while in the female, abortion and stillbirths 
are common. 

Mercury. — Poisoning with mercury may be acute, subacute, or 
chronic. The first is due especially to the corrosive chlorid and other 
mercuric salts; the second, to calomel or small doses of those of the 
former group. Chronic poisoning occurs as a result of inhalation of 
fumes or dust containing mercury, and is seen in workmen in 
mirror manufactories. In the acute cases violent inflammatory and ne- 
crotic lesions of the gastro-intestinal tract are seen. Parenchymatous de- 
generation, fatty change, and even calcification of the renal epithelium, 
especially of the convoluted tubules and the ascending limb of Henle's 
loop, may occur; fatty degeneration in other organs may sometimes be 
met with. In subacute cases marked by ptyalism some change in doubt- 
less present in the salivary glands, but the nature of this has not been 
determined. 

Ergot is a poison having as its principal action the increase of blood 
pressure especially by constriction of the smaller vessels due to the pres- 
ence of certain amines which act upon the sympatheic nervous sys- 
tem. Acute poisoning sometimes results from overdosage, while chronic 
intoxication occurs from the use of affected grain, particularly in famine 
years. Wide spread poisoinng of communities has sometimes resulted. 
The lesions produced are not definite or uniform. Gastro-intestinal 
inflammation and erosion of the mucous membrane have been observed, 
but are not constant; sclerotic change in the spinal cord has been found in a 
few cases. Gangrene is a frequent lesion, probably resulting from vascular 
obstruction due to contraction of the blood-vessels. Enlargement of the 
spleen has sometimes been noted. 

Toxalbumins from Plants. — Certain vegetable bodies, like ricin, de- 
rived from the castor bean, and abrin, derived from jequirity bean, are 
exceedingly toxic, acting in part as blood-poisons, but also as parenchyma 
poisons. Injected into animals these substances cause violent intoxica- 
tion and focal areas of necrosis in various situations, notably in the 
liver. In part these lesions result from vascular thrombosis, in part, 
from direct action. The study of the action of these poisons is of par- 
ticular interest from the resemblance of the lesions to those caused by 
certain bacteria and bacterial poisons. 

Toxic Products of Bacteria. — In the growth and multiplication of 
various bacteria definite toxic substances are created, and through the 
latter the lesions of infection are to a large extent produced. Such 
poisonous bodies may be generated in the growth of the bacteria out- 



THE ETIOLOGY OF DISEASE 



37 



side of the body, as well as within the body. In the latter case the 
pathological lesions at the point of infection may be the focus of origin 
of toxic substances which are then distributed throughout the body. 
This is eminently true of tetanus and, to a large degree, of diphtheria. 
In other cases the bacteria themselves are transported to various parts 
of the body and, finding lodgment in the tissues, set up changes by 
which their toxic products are evolved. The latter increase the local 
foci of pathological change and then spread in the circulation and cause 
general intoxication. Further reference to these poisons will be made 
when discussing the individual bacteria. 

The venom of serpents and of various insects contains toxic bodies^ 
some of which are protein in nature. They vary in their action, being 
to some extent blood-poisons, but more particularly parenchyma poisons. 
The lesions produced are local and general. Locally, there are intense 
inflammatory reaction and edema around an area of cellular necrosis or 
destruction where the poison has come in immediate contact with the 
tissues. The blood seems to suffer great disorganization and corpuscular 
change, hemolysis being especially noteworthy when venom is deposited 
locally and slowly absorbed; when a large quantity is thrown into the 
circulation intravascular clotting is apt to occur. Petechial hemorrhage 
and foci of cellular necrosis occur in various organs, and edema of the 
lungs is frequently present. The action of the venom of different animals 
varies in kind and intensity to a certain extent, but is, in general, of a 
similar type. Snake-venom has the peculiarity of setting up immunity 
reactions similar to those induced by bacterial toxins. It contains several 
different fractions, those toxic to blood, nervous tissue, kidney, etc. 

Blood-poisons. — Various liquid or gaseous substances are termed 
"blood-poisons" because of their especial action upon this tissue. The 
blood-poisons may be classified as (a) those which combine with the 
hemoglobin without changing the corpuscles; (6) those which alter the 
red corpuscles and the coloring-matter; (c) those which affect the blood 
as well as the tissues generally; (d) those which cause changes in the 
blood-plasma, increasing or decreasing the tendency to clotting; and (e) 
those which destroy leukocytes. 

(a) Among the poisons which act by entering into combination 
with the hemoglobin without changing the corpuscles, carbon monoxid, 
cyanogen, and hydrogen sulphid are important. In carbon-monoxid 
poisoning, which is commonly seen in illuminating gas poisoning, the 
blood has a light color while petechial hemorrhages and fine areas of 
necrosis may be seen in various parts of the body especially in the brain. 
In cyanogen-poisoning the blood is similarly light in color; while in H 2 S- 
poisoning the blood is often dark, sometimes quite black. 

(b) Among the poisons which disorganize the blood-corpuscles and 
later the hemoglobin are a large number of chemical agents used in 
medical practice or in the arts, including potassium chlorate, nitro- 
glycerin, anilin, nitrobenzol, various coal-tar derivatives, and arseni- 
uretted hydrogen. Certain poisonous plants (toadstools) act similarly. 
These poisons lead to a reduction of the hemoglobin with formation of 
methemoglobin and at the same time destruction of the corpuscles 
themselves, with release of the hemoglobin into the serum. The altered 



I 



38 A TEXT-BOOK OF PATHOLOGY 

condition of the blood often induces secondary changes, such as fatty 
degeneration and hemorrhages in various organs. The blood-corpuscles 
are found in variously degenerated conditions, showing microcytosis 
and poikilocytosis in particular. Nucleated red corpuscles may be 
present as in other conditions of blood destruction with attempted 
regeneration. 

(c) Among the poisons which disorganize the blood and at the same 
time cause changes in the parenchyma of organs, reference has been 
made to abrin and ricin. In addition to the organic changes, these 
substances cause certain alterations in the blood itself, increasing the 
coagulability and thus inducing thrombosis. 

(d) Various substances introduced in sufficient quantity are capable 
of affecting the plasma of the blood or the corpuscles in such a way as 
to affect its coagulability. Calcium salts, carbonic acid gas, and fibrin 
ferment are active in this way, but the last alone produces toxic results 
through this function. Ferment intoxication may occur in consequence 
of various other intoxications, when corpuscular or tissue destruction 
has liberated the ferment. Among the poisons which decrease coagula- 
bility peptone is important. 

(e) Saponin and benzol reduce the number of leukocytes apparently 
by destroying or inhibiting the centers of their production in the bone 
marrow. 

Injection of large quantities of water or hypotonic salt solution may 
have a hemolytic effect. 

The blood-serum of one individual may contain hemolytic agents 
for the cells of another person, and more frequently for those of another 
species. 

Nerve-poisons. — This group contains a large number of substances 
capable of producing violent symptoms and even death without definite 
change in the tissues of the body. Some investigations showing cer- 
tain alterations in the finer structure of the nervous system in disease 
and in cases of intoxication suggest that histological changes in the 
central neurons may be found to result from poisoning by these sub- 
stances. Changes of this kind (changes in size and form of the cell and 
nucleus, thickening, contraction, or disappearance of dendrites, altera- 
tions in the chromophilic bodies, etc.) have been described in the gray 
matter of animals poisoned with alcohol and certain toxins of bacterial 
origin. It is not unlikely that similar changes will be found in other 
conditions. Among the nerve-poisons are alcohol, chloroform, ether, and 
various alkaloids like morphin, atropin, etc. In this same group might 
be included some of the poisons contained in the venom of serpents and 
other animals, but these usually cause definite lesions in the blood or 
tissues of the body. 

Ptomain Intoxications. — Another group of poisons with action similar 
to the last are those produced within the body by putrefaction or in 
various foodstuffs before ingestion. Frequently cases have been observed 
in which all the members of a family or even large numbers of people 
have been poisoned by eating certain meats, sausages, ice-cream, and 
other foods. In some of these cases it has been stated that the 
toxic element was a basic compound resembling the alkaloids in 



THE ETIOLOGY OF DISEASE 



39 



chemical structure, to these putrefactive compounds the name ptomain 
is given. 

There is a tendency, and possibly a correct one, to discard the idea 
that ptomain poisoning as such occurs at all and to explain that condi- 
tion as one of bacterial infection or intoxication. The history of certain 
cases, however, leaves the matter as yet imperfectly settled for, while it 
may be impossible to isolate ptomains in any quantities or at all from 
the body, they may have been destroyed, and the attack has at times 
appeared too shortly after ingestion of certain foods to have arisen from 
poisons made within the body; it is also impossible at times to isolate 
pathogenic organisms. However, it is asserted that the poisons can be 
and usually are made before the food is ingested and that they are to be 
considered as bacterial toxins. Such is indeed the case in the conditions 
known as "botulism" and "meat poisoning" where the organisms in 
question produce a heat resistant, easily absorbable poison with a 
powerful action upon nervous tissue, blood and its vessels and cause an 
irritative enteritis. 

VEGETABLE AND ANIMAL PARASITES 

Vegetable parasites are by far the most important causes of dis- 
ease. The belief in a living cause or contagium vivum is by no means 
a recent acquisition, but the actual demonstration that diseases may be 
caused by minute living organisms was one great achievement of the last 
part of the nineteenth century. The micro-organisms in question (bac- 
teria) belong for the most part to the vegetable kingdom and constitute the 
lowest orders of fungi. Their biological characters and theri relations to 
special diseases will be described in a subsequent chapter. 

Etiological Relationship of Bacteria to Disease. — It is difficult to 
prove the specific relation of bacteria to disease. Koch has laid down 
four important laws which must be conformed with before the etiolog- 
ical role of a bacterium is admitted. These are: (1) The bacterium 
must be found in the diseased person; (2) it must be cultivable upon 
media outside the body; (3) pure cultures introduced into a healthy 
animal must produce the disease in the animal; and (4) the bacterium 
must be recoverable from the body of the animal. In a number of dis- 
eases micro-organisms have been proved to be the specific causes 
according to the requirements of Koch's rules. In other diseases it has 
not been possible to furnish absolute proof, though the presumptive 
evidence, furnished by constant occurrence of the bacteria, suggestive 
association with the lesions of the disease, absence of the bacteria in 
other diseases, etc., is sufficient to satisfy all but the most skeptical. 

Classification of Diseases Due to Bacteria. — The general term 
infectious disease is applied to all such as are caused by bacteria. In 
some cases the diseases are readily communicated from person to person, 
even though contact has not been immediate. These are termed con- 
tagious diseases, while the term non-contagious is given to those in which 
such ready transference is not observed. As a matter of fact, the dis- 
tinction is artificial. Any infectious disease may be communicated 
from the diseased to the healthy if the causative agent be transferred. 
In some diseases this transference readily occurs, even through the air 



40 



A TEXT-BOOK OF PATHOLOGY 



and at considerable distances; in others actual contact is necessary; 
while in still others secretions or excretions of the diseased must be con- 
veyed to the healthy. Contagiousness is, therefore, a matter of degree 
only. It is better to use the terms communicable or transmissible dis- 
eases for those in which every case is dependent upon a preexisting one, 
the mode of transmission being either direct or indirect. Malaria is an 
indirectly transmissible disease requiring the intervention of the mos- 
quito, while diphtheria is a directly communicable infection, no agent 
being required for its spread. 

Infectious diseases may be at times spread in communities, affect- 
ing large numbers of people. Such a dissemination is termed epidemic, 
and the disease an epidemic disease. When the disease spreads over 
large areas, as a whole country or continent, the term pandemic dis- 
ease is applied. Other infections are constantly present in a locality; for 
such the terms endemic and endemic disease are used. Some endemic 
diseases are restricted to certain localities and seem in some measure 
dependent upon local conditions (of atmosphere, soil, etc.) for their con- 
tinuance. These are called miasmatic diseases. The soil, etc., has, of 
course, nothing directly to do with disease, but merely affords the con- 
ditions necessary for the propagation of the infecting agent, as, for 
example, swamps and the malarial mosquito. 

Infectious diseases are frequently described as local or general. 
Local infections are those that present specific pathological change in a 
restricted part of the body but it is a mild infection indeed if all the body 
be not in some way affected. In erysipelas and diphtheria the kidneys 
and heart are affected although the gross appearance is of a local lesion; 
impetigo is a mild local affair with no general manifestation. General 
infections are marked by an immediately generalized disease, as in 
typhus fever or plague. Strictly speaking, most if not all of the 
so-called general infections are at first local. Among purely local infec- 
tions might be named, the diseases of the skin due to vegetable micro- 
organisms. 

Entrance of Micro-organisms into the Body. — Bacteria may be 
inhaled or swallowed, may enter through abrasions in the mucous 
membrane or skin, and may be transferred in utero from the maternal 
to the fetal blood. The mode of entrance in individual diseases de- 
pends upon the nature of the bacterium, its habitat, and surrounding 
conditions. Some may enter in but one way; others gain access in any 
of the different ways. Details regarding this subject will be given in 
the discussion of special infections. 

Animal parasites of various kinds act as causes of disease. This 
group of diseases is termed the parasitic diseases or invasion diseases. 
In some instances microparasites cause a clinical picture similar to that 
of infectious diseases (malaria, dysentery, trichinosis) ; in other cases the 
manifestations bear little resemblance to infections. 



CHAPTER II 



DISORDERS OF NUTRITION AND METABOLISM 

Food. — In the life of the organism certain substances are needed 
for growth, for the repair of tissues consumed in the wear and tear of 
life, and to supply heat and other energy. Among these foods are 
proteins, carbohydrates, fats, inorganic salts, and water. A continuance 
of normal existence requires more or less definite proportions of the first 
three and at least a sufficiency of salts and water. In addition to the foods 
named certain as yet not very clearly identified substances normally 
contained in fresh foods seem to be necessary to nutrition. These sub- 
stances have been called vitamins and their absence from the diet is held 
responsible for certain, so called, deficiency diseases. The amount of 
food and the exact proportions vary somewhat in individual cases and 
under varying circumstances. Voit, the pioneer in this work, found that 
a laboring man under ordinary conditions requires 118 gm. of protein, 
56 gm. of fats, and 500 gm. of carbohydrates. This diet contains 3055 
calories. Recent studies all tend to show that the amount of protein is 
beyond actual needs and that some reduction of Voit's figure may be 
made without injurious results and possibly with advantage, 
though the low protein figures of Chittenden and others err on the other 
side. The minimum amount compatible with healthy nutrition is per- 
haps from 60 to 70 gm. The weight of the individual and the amount of 
the daily work must determine the requisite diet, 35 calories per kilo of 
weight being an average figure for a man doing light work. The proteins 
of the diet are necessary to restore tissue waste, since the organism can- 
not build up proteins from simpler compounds. During growth and in 
convalescence from wasting diseases larger amounts of proteins are required 
for tissue building. This consumes part of the nitrogenous foodstuffs. 
The rest, with most of the fats and carbohydrates, is mainly useful in 
contributing energy. 

Diminished Supply of Food; Inanition; Starvation. — Either 
the want of food or diseases of the digestive organs with lack of ab- 
sorption may lead to insufficient nourishment. This causes a loss of 
body weight, as the necessary heat-producing and energy-giving sub- 
stances must be supplied to maintain fife, and the tissues are consumed 
for this purpose. During the first two to five days of starvation in 
previously well-nourished persons the glycogen supply of the body is 
largely consumed, and the amount of protein consumption is corre- 
spondingly less than on subsequent days. In prolonged starvation the 
average requirement of from 28 to 32 calories per kilo has been found 
quite constantly, and with like constancy about 13 per cent, of this 
energy is supplied by protein and 87 per cent, by fat. In fat persons or 

41 



42 



A TEXT-BOOK OF PATHOLOGY 



animals the amount of protein consumption is relatively less than in 
those less supplied with fat. Toward the end of long fasting periods the 
nitrogen elimination falls to low figures. At the same time the urea- 
nitrogen is especially reduced, partly on account of the reduction of 
exogenous proteins in the metabolism and partly on account of acidosis. 
(See Acid Intoxication.) A " premortal rise" in nitrogen elimination 
may occur at the end of long continued inanition. The subcutaneous 
and other fat depots suffer first in the emaciation of starvation; later, the 
glandular organs, muscles, nervous system, bones, and heart. The chlorids 
in the urine are regularly diminished, while calcium salts are increased in 
correspondence with the destruction of osseous tissue. 

The functions of various organs suffer greatly: the respirations and 
heart action are weak, muscular exertions are reduced to a minimum, 
the endurance and nervous force decline, the body temperature sinks, 
and finally death may occur from exhaustion or secondary affections 
consequent upon the disturbed nutrition. (See Acid Intoxication.) 
The blood in starvation preserves its chemical constitution and corpus- 
cular richness surprisingly, even after prolonged abstinence. There is 
probably a reduction in the total mass of blood. Marked acidosis may 
accompany fasting and excessive amounts of acetone bodies may be 
excreted in the urine. Repeated fasting seems to lessen this tendency 
somewhat. 

Increased Supply of Food; Overfeeding. — The effect of this 
depends upon individual conditions, such as the amount of exercise, 
the surrounding temperature, the clothing and condition affecting health 
generally. The effect of overfeeding differs in individuals in consequence 
of various conditions affecting the digestive apparatus, the nervous 
system and the endocrine glands (glands of internal secretion). An excess 
of protein food leads to increased excretion of the end-product of its 
metabolism — urea. Experiments have shown that to a slight extent a 
reserve amount of albuminous tissue may be built up by excess of protein 
food. During growth and after wasting diseases such retention of nitro- 
gen in the upbuilding of tissue is of course pronounced, and is not to be 
interpreted as " reserve protein." Great excess of protein eventually 
disturbs digestion and leads to its own discharge with the feces. 

The carbohydrates and fats are broken up in the body and excreted 
mainly as carbonic acid and water. An excess of these foods tends to 
cause increased deposition of reserve fat and glycogen, which may be 
called upon at subsequent times of need. This deposition is a normal 
or physiological process and has the distinct purpose just indicated. 
Exceptionally in the condition called obesity the storing up of fat is 
inordinate and clearly patholocigal. 

Metabolism of Fat. — The fat of the body has two sources: the fat 
of the diet and sugar either ingested or made within the body. In the 
case of ingested fats the deposited fat is of like composition, and may, 
therefore, be widely different in its composition from the fat peculiar 
to the species; in the case of fat made from sugar it is always specific 
for the species. Thus, a dog fed upon mutton fat deposits mutton fat in 
his tissues, while in making fat from sugar fat peculiar to his species and 
differing from mutton fat is deposited. The sugar from which fat is 



DISORDERS OF NUTRITION AND METABOLISM 



43 



built up may be ingested as such or may be derived from the carbo- 
hydrates, fats, or proteins of the diet or tissues. 

Causes of Obesity. — Excessive ingestion of food by persons having 
active digestion and leading sedentary lives may occasion unusual depo- 
sition of fat. It is difficult, however, to determine the limits between 
physiological and pathological fatness. In some cases patients assert 
that the amount of food has not been excessive, and this may be actually 
true. Obesity in such individuals is undoubtedly pathological and due to 
some inherent abnormality of metabolism. A further proof of the ex- 
istence of such a tendency is seen in certain families in which excessive 
fatness is common, even in childhood. The relation of disorders of the 
endocrine glands to obesity is indicated by the fatness which occurs at 
the menopause in women or after removal of the ovaries, by that of males 
after castration and by the abnormal nutritional conditions and obesity 
seen in diseases of the thyroid gland and hypophysis. The nature of this 
metabolic disorder is obscure. It has often been held that the power of 
oxidation is lacking, and, as a matter of course, the amount of oxygen 
consumed is deficient in comparison with the amount of food ingested. 
This must be true or the fat could not accumulate; but it remains to be 
shown whether the diminished oxygen consumption is the primary 
cause or only an incident in the disease. Experimental investigations 
have shown that the basal heat production (that exhibited by the 
normal body when fasting and with the external temperature at 37° C.) 
is not exceeded in a downward direction in obesity, though the figure 
may be consistently low in this condition. The explanation of this 
circumstance may be found in the fact that in fat persons equivalent 
weights represent an undue amount of inactive (adipose) tissue, and 
that large deposits of subcutaneous fat afford an external protection 
against loss of heat; consistently low figures of heat requirement may, 
therefore, indicate, if not pathological, at least continuously low, oxida- 
tion ; and it is possible that the methods of observation and the range of 
error of these methods may prevent the detection of slight deficiencies in 
oxidation that in the long run (over periods of weeks or longer) could 
explain fatty accumlations. Some experiments seem to indicate retarda- 
tion of oxidation though no actual reduction. 

Pathological Anatomy. — The excessive adipose tissue in this condi- 
tion is found in the skin and subcutaneous tissues, in the omentum and 
peritoneum, around the kidneys, heart, and mediastinal tissues, in the 
liver, and less commonly elsewhere. The amount varies from slight 
excess to monstrous deposits. Secondary changes in the organs (notably 
the heart muscle) may be due to pressure or functional inactivity. 

Associated Conditions. — Fatness is more or less closely related to 
certain other diseases of metabolism, such as diabetes and gout. Anemia 
is frequently present and has sometimes been regarded as a cause, oper- 
ating by reducing oxidation. 

The occurrence of fatness in certain types of nervous disease, such as 
hysteria and idiocy, suggests a nervous perversion of fat metabolism, 
though possibly other conditions, for example, disease of the glands 
of internal secretion, may be fundamentally involved. 



44 



A TEXT-BOOK OF PATHOLOGY 



Excessive Tissue Destruction. — This has been referred to in con- 
nection with inanition; but it may be independent of the amount of 
food ingested. Among the conditions in which this is observed 
may be mentioned fever, infectious or of other forms; chronic infectious 
diseases, with or without fever; tumors, especially carcinoma; intoxica- 
tions of various sorts; some cases of Graves' disease, etc. In all of these 
conditions the fats of the body may waste as in simple inanition; but 
there is an early and marked tendency to consumption Of the more 
important protein structures. 

The nature of the metabolic disturbances in these cases is obscure^ 
though it is likely that toxic substances of various sorts are the direct 
causes. This is most probable in the case of direct intoxications (phos- 
phorus), but is also likely in other cases. In carcinoma, as well as in 
fevers, there are doubtless poisonous substances in the blood, but whether 
these are the causes of the metabolic changes or not requires further 
study. It is now well known that in Graves' disease metabolism is 
increased, the basal metabolism being greatly in excess of the normal, 
and to this is attributable the emaciation of such patients. The in- 
creased metabolism is regarded as a result of increased output of thyroid 
secretion. The fact that thyroid extract is capable of causing excessive 
destruction of tissue in normal or obese persons is significant in this 
connection. 

Acidosis. — In the final metabolic transformation of protein there 
are produced ammonium, urea, kreatinin, and other nitrogenous sub- 
stances. The formation of urea is still obscure in some particulars. It 
is certain that a large part is produced in the fiver and some is formed in 
the glandular organs. The intermediate steps in the manufacture of urea 
have not been definitely determined, but it is known that the liver i& 
capable of converting ammonium salts directly into urea, and it is prob- 
able that ammonium is an important intermediate product of protein 
transformation. An excess of acids in the body (either from introduction 
from without or production in the body) is in part neutralized by alkaline 
bases in the blood and tissue juices and in part by ammonium. In 
consequence of this consumption of ammonium the urea of the urine 
decreases and the ammonium salts are increased. The quantity of such 
salts is, therefore, in a measure an indication of the condition which has 
been termed " acidosis." When the fixed alkalies (sodium and potassium) 
are more or less exhausted in the neutralization of acids, symptoms of acid 
intoxication result. Fortunately, this is at first prevented by the abun- 
dance of ammonium, but in marked cases of acidosis the ammonium 
does not suffice. 

The loss of reserve alkali of the body by combination with acids and 
elimination through the kidneys reduces the C0 2 -carrying capacity of the 
blood, sometimes to such a degree that instead of a normal capacity of 
40 volumes per hundred the figure may be reduced to 20 or less. There 
is of necessity also reduction in the C0 2 - tension in the alveolar air and the 
determination of thes*e values is utilized as a practical method of recog- 
nizing the presence and grade of acidosis. In renal disease a state of 
acidosis may be dependent on the inability of the kidney to excrete 
acid salts. 



DISORDERS OF NUTRITION AND METABOLISM 



45 



Experimental acidosis is easily produced in animals by feeding them 
foods deprived of alkaline bases or by direct administration of acids. In 
the former case the acids (sulphuric from the sulphur of albuminous food, 
and phosphoric from the phosphorus) resulting from transformation of 
food and tissues must be neutralized by the alkalies of the body and the 
ammonium incidental to the process of urea formation in the liver; in the 
latter case there is direct excess of acid. Such acidosis is readily produced 
in herbivorous animals, as the amount of protein food is small, and in 
consequence but little ammonium is produced. Various nervous symp- 
toms are observed. The animal breathes quickly, the pulse grows rapid, 
muscular weakness, ataxia, and tremor develop, and finally coma or col- 
lapse terminates the disease. The administration of alkalies may com- 
pletely arrest the progress of the condition and full restoration may occur. 

Acidosis in Man. — Somewhat similar symptoms are seen in man in 
certain diseases in which increased elimination of ammonium, with de- 
crease of urea and the excretion in the urine of certain organic acids, 
have been discovered. The assumption is warranted that these are cases 
of acidosis. 

Etiology. — Among the conditions in which this occurs are fever, 
diabetes, carcinoma, acute yellow atrophy of the liver, narcosis, severe 
anemia, phosphorus-poisoning, advanced gastro-intestinal disease, 
and inanition. Clinically diabetic acidosis is the most striking and severe 
form. Sometimes no discoverable cause can be detected (cryptogenic 
acidosis). Gastro-intestinal disorders are very possibly the occasion of 
this form of obscure acidosis. Poisons produced in the intestines may, 
perhaps, set in play the metabolic disturbances which terminate in over- 
production of acids. 

Among the acids concerned are lactic, sarcolactic, sulphuric, phos- 
phoric, but especially diacetic and beta-oxybutyric. These in part 
combine with the fixed alkalies and with ammonium, and in part are 
<excreted as such. Some, as sarcolactic acid, usually suffer decomposition 
in the body, and are, therefore, rarely met with in the urine. The im- 
portant acids are the ketonic acids, (3. oxybutyric and its derivative, aceto- 
acetic (diacetic) . By reverse action the former may be derived from the 
latter. Acetone, so important as a clinical indication through its peculiar 
sweetish odor imparted to the expired air, is probably formed at the 
places of elimination (lungs and kidneys) from aceto-acetic acid. 

The ketonic acids, beta-oxybutyric and aceto-acetic, are now known 
to be due very largely to the combustion of fat. In normal cata- 
"bolism of fat there is first a cleavage into glycerol and fatty acids. The 
former is converted into sugar; the latter oxidized in successive stages 
until the higher acids are converted into butyric acid. At this stage 
the process of oxidation becomes somewhat changed, and beta-oxy- 
butyric acid, aceto-acetic acid, and, finally, through acetic and formic 
acid, the end-products (carbon dioxid and water) are produced. At 
the stage of aceto-acetic (diacetic) acid, a side reaction occurs whereby 
acetone is formed. Normally this occurs to the extent of traces only, 
but when fat is burned in large quantities the acetone formation in- 
creases considerably beyond the proportionate increase of the fat con- 
sumption. In diabetes and sometimes in other conditions in which 



46 



A TEXT-BOOK OF PATHOLOGY 



considerable fat consumption takes place, either from lack of carbo- 
hydrates, or as a result of the excess of fat catabolism or from failure of 
certain fermentations concerned, the conversion of beta-oxybutyric 
and aceto-acetic acids into end products is halted or diminished and the 
blood is flooded with the ketone acids, which then act injuriously by 
abstracting bases from the tissues or as direct poisons. 

The ketone bodies undoubtedly may be derived to some extent from 
protein decomposition, especially from the amino-acids leucin, tyrosin 
and phenyl-alanin. 

There is always reduction of oxidation in cases of acidosis but it is not 
known whether this is the primary disturbance or whether it is but an ac- 
companiment. Experimentally it has been shown by several observers 
that diminution in the supply of oxygen will lead to increase of these 
acids. They owe their presence to excessive production and to the fail- 
ure of the normal oxidation. Other substances may result from protein 
destruction with insufficient oxidation. Among these are the amino- 
acids, leucin and tyrosin, as well as lactic acid, found in the urine in 
phosphorus-poisoning and acute yellow atrophy of the liver as well as 
in other conditions. 

The symptoms of acidosis in man may be quite similar to those seen in 
experiments upon animals. Marked dyspnea (air hunger), rapidity of 
the pulse, depression, stupor, and deep coma (coma carcinomatosum, 
diabeticum) are some of the more pronounced manifestations. The ex- 
planation of the symptoms occurring in acid intoxication is not entirely 
clear. The extreme dyspnea, which is one of the most characteristic 
symptoms, was first naturally referred to asphyxia; but as it has been 
found that the blood contains an adequate amount of oxygen and a 
greatly diminished quantity of CO2, this explanation cannot hold. It is 
probable, however, that the dyspnea is due to the inability of the blood 
to carry off carbon dioxid from the cells, in consequence of the reduction 
of available alkali owing to its fixation by the acids. There is thus a 
decrease of oxidation from the accumulation of carbon dioxid in the cells, 
but not asphyxia in the ordinary sense of the word. Some have believed 
that the symptoms of acid intoxication are due to certain as yet unknown 
toxins which are produced at the same time as the acids. There is no 
direct proof of this, and the evidence at hand would indicate that the acids 
in themselves, by reducing the available alkaline bases of the blood and by 
disturbing the metabolic processes in the cells, are sufficient to cause the 
symptoms. The direct action of the acids themselves must be held as 
the probable factor in the production of the symptoms. 

Disorders of Protein Metabolism. — Proteins are complex bodies 
made up of combinations of various amino-acids in proportions differ- 
ing widely in the proteins of the various tissues of the body and in those 
of different species. Within the gastro-intestinal tract the digestive 
ferments convert proteins into proteoses and peptone, and finally into 
the constituent amino-acids. There are thus set free the elements 
from which reconstruction of proteins of composition characteristic 
of the species in question can be effected. Some of the amino-acids 
from the foreign protein of the food may be unsuitable for the recon- 
struction of these new proteins, while some may be present in super- 



DISORDERS OF NUTRITION AND METABOLISM 



47 



fluous amount. These fractions are catabolized and excreted in the 
form of end-products. The major part is used for the resynthesis of 
protein. This was until recently thought to occur exclusively in the 
wall of the intestine, so that there should be delivered into the blood 
re-formed proteins similar to those of the blood. More recently it has 
been learned that the amino-acids are absorbed, in part at least, into 
the blood and utilized for rebuilding of new protein in the liver or other 
tissues. During youth and the growth period and after exhaustive 
wasting of the tissues considerable portions of the food proteins may 
be utilized directly for the upbuilding of the tissues. At other times 
only a small portion is thus utilized to repair the waste of cells and to 
replace dead cells. The greater part of protein food is quickly catab- 
olized and excreted. The level of protein content of the blood is 
maintained very tenaciously, and in case of starvation the blood ab- 
stracts proteins from the cells to maintain the level, while as a result 
of overfeeding some of the protein is deposited as a storage within cells, 
while the larger part is quickly catabolized. There is no capacity for 
storage of protein comparable to the storage of carbohydrates, as glyco- 
gen in the liver and muscles, or of fat in the various areolar tissues. 

The catabolism of proteins is exactly comparable to their digestion 
in the intestinal tract, but takes place within the cells under the influence 
of endotrypsin. First proteoses and peptone are formed, then amino- 
acids, and, finally, end-products varying somewhat with the source 
of the protein involved. The exogenous proteins, those derived directly 
from food, are mainly excreted as urea and ammonium; the endogenous, 
those of the tissues of the body, when catabolized yield only small 
portions of the urinary urea and ammonium, and those of the muscles 
in particular are excreted as creatinin. The latter substance is derived 
from the creatin of muscles, which in turn is probably an anabolic 
product of amino-acids made by a special muscle metabolism. 

In the normal man excess of protein feeding is speedily followed by 
marked increase of elimination of the end-products, urea and ammo- 
nium. Only a fractional retention occurs. In certain pathological con- 
dition, such as nephritis and gout, considerable nitrogen retention may 
occur, especially in the form of non-protein nitrogenous bodies. In 
fasting and starvation the nitrogenous elimination falls to very low 
levels, in which the exogenous nitrogen end-products (urea and am- 
monium) are specially affected. The amount of creatinin is maintained 
at a quite fixed level, being reduced only to the extent of the subtrac- 
tion of the relatively small airlount of creatinin derived from the meat 
and meat extracts of diet.. 

Under conditions of rapid catabolism of protein, such as in leukemia, 
carcinoma, and internal suppurations, the proteoses and peptone may 
be liberated in such quantity as to be in part excreted in the urine (pro- 
teosuria, peptonuria, albumosuria). These proteoses and peptones, 
however, being derivatives of native protein, are non-toxic, contrasting 
with the toxic proteoses and peptone derived from foreign proteins in 
the digestive tract. Whether or not any of the latter are absorbed into 
the blood and excreted in the urine in pathological conditions is un- 
certain. In certain other conditions of rapid protein catabolism (as 



48 



A TEXT-BOOK OF PATHOLOGY 



in autolytic destruction of liver substance — acute yellow atrophy, phos- 
phorus-poisoning, etc.) amino-acids may be excreted in the urine. 

In the catabolism of protein, under conditions in which the utiliza- 
tion of carbohydrates is greatly reduced, as in diabetes, considerable 
sugar may be an end-product. This is derived from the amino-acids, 
which lose their NH 2 by a process of deaminization and yield oxy- 
fatty acids, which are finally converted into dextrose. This process may 
account for much of the persistent dextrosuria of severe cases of diabetes 
after the glycogen storage has been exhausted and the diet has been 
deprived of all carbohydrate matter. 

Creatinin elimination in the urine may be utilized as an indication 
of the state of muscle metabolism. In cases of rapid muscular waste 
from fever or other causes an excessive output of creatinin is met with; 
and in certain extreme cases creatin itself — the substance in muscle 
from which creatinin is derived — is thus excreted, probably as an ex- 
pression of failure of conversion into creatinin. In muscular dystro- 
phies the elimination of creatinin may be decreased. 

Disorders of Purin Metabolism. — By purin metabolism is meant 
the metabolism of cellular nuclei. The nuclei contain nucleoproteins 
which are combinations of globulin and nucleic acid, the latter being com- 
posed of phosphoric acid, pentose-sugar, and a base, either purin or pyrim- 
idin. The important purin bases are the aminopurins, adenin and 
guanin, and the oxypurins, hypoxanthin and xanthin. In the normal 
purin catabolism there is first a separation of the globulin and nucleic 
acid, and then, under the influence of special enzymes, the latter is broken 
up into its components and the purin bases deaminized and oxidized to 
uric acid. In the final urinary excretion both purin bases and uric acid 
are present, so that the catabolism does not wholly proceed to the end- 
product. Under ordinary conditions of diet the urine contains more 
purin of exogenous than of endogenous origin. The foods that yield 
this are such cellular gland foods as thymus, pancreas, liver and kidney, 
and, to a *less extent, muscle (meat); leguminous vegetables; and coffee, 
tea, and cocoa. On a purin-free diet the excretion falls to a low level of 
fair constancy. Apparently the exogenous purins are excreted in toto, 
no part being utilized in the anabolism of nucleic acid. Uric acid was 
formerly believed to be convertible into urea within the body but recent 
studies seem to prove this impossible. 

Under normal conditions the blood contains from 1.5 to 2.5 mg. of 
uric acid in 100 c.cm. Under certain circumstances this quantity may 
rise to 8 or 10 mg. either temporarily er for longer periods. Among 
these conditions are chronic nephritis, gout, lead-poisoning, after heavy 
feeding on purin foods, during resolution of pneumonia, in sepsis, leuke- 
mia, etc. In the last three of the conditions named there is excessive 
cellular metabolism and consequently temporary overproduction of purin 
bodies. In the first three the higher level of uric acid is probably due to 
some alteration of the renal permeability which maintains a higher 
threshold for the elimination (see below), rather than to any increased 
production of uric acid, or in the case of gout to the presence of uric acid 
in the blood in some sort of chemical combination preventing its normal 
excretion. 



DISORDERS OF NUTRITION AND METABOLISM 



49 



Gout. — In its typical form gout is a paroxysmal disease marked by 
deposits of urates in the joints and other structures, and by coincident 
or consequent inflammatory disturbances. There are many varieties, 
however, of irregular gout in which the paroxysms may be partly or 
wholly wanting, and in which the disease takes the form of a general 
systemic disorder, or of organic maladies of various sorts. 

Etiology. — Gout is essentially a hereditary affection, the heredity 
not rarely being polymorphous. By this is meant that in certain families 
gout and other diseases, such as obesity, diabetes, and arterial sclerosis, 
may occur interchangeably. Gout usually develops in the later years of 
of life, and among the contributing causes are the use of alcohol, over- 
eating, sedentary life, and chronic lead-poisoning. 

Pathological Anatomy. — The conspicuous anatomical lesions are 
those of the joints, and consist of the deposit of acid urate of sodium in the 
cartilages and connective tissue, and secondary inflammatory changes. 
The latter may cause great distortion and fibrous overgrowth. Similar 
urate deposits may occur in the cartilages of the ear, eye, and nose, and 
in the subcutaneous connective tissue or elsewhere. These deposits, 
called the gouty tophi, may subsequently disappear by absorption or by 
discharging through the skin. Fibrosis in various organs and tissues 
of the body frequently occurs in the course of gout. Among these the 
fibrotic or gouty kidney is most important. Atheroma, cirrhosis of 
the liver, hypertrophy and fibroid change in the heart, and chronic val- 
vular disease are also frequent. 

Pathogenesis. — For a long time some disorder in the formation and 
excretion of uric acid has been held responsible for the manifestations of 
gout. 

Garrod first demonstrated an excess of uric acid in the blood, and 
recent exact chemical studies have confirmed this observation. There 
are, however, as has been shown, diseases, such as leukemia, nephritis, 
and pneumonia, in which excess of uric acid in the blood occurs without 
any of the results seen in gout. It is possible, of course, that the accu- 
mulation in the blood may be due to different causes in these conditions, 
but it is evident that other factors beside the mere presence of excessive 
uric acid are operative in gout. 

The excretion of uric acid in the urine is found reduced just before an 
acute paroxysm of gout; it increases above the normal during the attack, 
and then falls to about the normal. In chronic cases without attacks 
the excretion is about normal. The increased quantity in the blood 
might then be due to increased production or to a reduced transforma- 
tion to simpler metabolic products. Neither of these explanations 
seems justified. At present the more probable reason seems to be a 
change in renal permeability (without any special renal lesion), as a 
result of which the threshold of excretion is raised or the presence of uric 
acid in some chemical combination retarding its excretion. The reduc- 
tion of uric acid before attacks has been attributed to the deposition 
of acid urate of soda in the joints and elsewhere, though the amount of uric 
acid in all the deposits falls far short of that which could explain this. 
Possibly changes in diet or intestinal absorption may play a part in this 
reduction. 
4 



50 



A TEXT-BOOK OF PATHOLOGY 



The pathogenesis of the urate deposits remains obscure. Ebstein 
first insisted that local necrosis, itself perhaps the result of excess of uric 
acid in the blood, is the direct occasion for the deposits, and some recent 
authorities believe that a primary and essentially gouty local inflam- 
mation invites urate deposits, the uric acid itself having no importance 
in the first condition. Experiments have, however, shown that uric 
acid is capable of causing local inflammatory lesions. Traumatism and 
circulatory conditions may play a part in localizing gouty precipitations. 

Diseases of Carbohydrate Metabolism.— The carbohydrates of 
the diet are converted into dextrose or glucose before absorption, this 
conversion being accomplished by salivary and gastro-intestinal en- 
zymes. After absorption into the blood the dextrose is converted into 
glycogen and stored in the liver cells, or, in cases of excess above the 
hepatic capacity of storage, in the muscles. Normally, there is a storage 
of glycogen sufficient to supply the nutritional needs for as much as five 
days; in fasting experiments it has been clear that the nu- 
tritional needs have been supplied by glycogen during the first few days. 
It has been a subject of much investigation and discussion whether or 
not other sources of sugar exist besides the ingested carbohydrates. 
Recent studies have shown beyond doubt that the amino-acids of protein 
catabolism may furnish considerable quantities of sugar by deaminization 
and subsequent conversion of the oxyf atty acids into glucose. In severe 
diabetes this may be a noteworthy source of sugar. It is conceivable 
that the glycerole derived from the splitting of fat may also furnish 
sugar, and this derivation seems probable, though it has not been definitely 
proved. 

The blood maintains a fairly constant sugar content under normal 
conditions — the amount being about 0.080 gm. per 100 c.cm. With 
normal quantities of sugar in the blood, glucose ordinarily fails to appear 
in the urine because a certain threshold of retention prevents its excretion 
through the kidneys. The threshold is, under conditions of normal 
renal permeability, about 0.170 gm. per 100 c.cm. When the blood 
sugar is reduced the glycogen stores of the liver will replace the loss. 
There is thus maintained a farily constant level of sugar concentration. 
When the sugar reaches a high level — beyond the storage capacities for 
glycogen in the liver and muscles — the excess is deposited as fat in the 
areolar tissues. Still higher levels of sugar concentration may exceed the 
capacity for storage as glycogen or fat and the threshold of renal per- 
meability. Glucosuria then results. 

Ultimately, sugar is oxidized in the muscles and converted into C0 2 
and H 2 0. The glycogen stores in the liver are in cases of need con- 
verted into dextrose, delivered to the blood, and finally burned in the 
muscles. The glycogen stores of the muscles are not available for 
maintaining the sugar content of the blood, but are utilized only by 
oxidation in the muscles themselves. 

Hyperglucemia. — Excess of blood sugar — a condition termed "hy- 
perglucemia" — may be a temporary result of ingestion of starches or 
sugar, or a more lasting condition in certain diseases (diabetes, thyroid 
diseases, hypophysis diseases, cancer). Under normal circumstances the 
liver is capable of storing as glycogen any amount of sugar derived 



DISORDERS OF NUTRITION AND METABOLISM 



51 



from mixed or starchy diet. The processes of digestion and absorption 
do not furnish sugar to the blood with sufficient rapidity to overbalance 
the storage capacity of the liver. Pathologically, the liver may fail 
to store the sugar and the excess in the blood may occasion excretion in 
the urine. In normal cases the blood sugar after a meal may increase 
in one or one and one-half hours to 0.100 or 0.125 per 100 c.cm., but the 
amount quickly falls to its former level. 

Alimentary Glucosuria. — When large quantities of sugar are ingested 
the capacity for storage may be exceeded and glucose may appear in the 
urine. Under certain pathological circumstances (diseases of the liver, 
alcoholism, thyroid disease) the ingestion of relatively small amounts of 
sugars may be followed by glucosuria (glucosuria e saccharo), and even 
starch ingestion may occasion a like result (glucosuria ex amylo). Some- 
times the glucosuria in such cases may perhaps be due to the fact that the 
liver is already stored to its capacity and cannot accommodate additional 
deposits of glycogen. 

Glucosuria Due to Excessive Hepatic Glycolysis. — Under certain 
circumstances the liver converts its stored glycogen into glucose so 
rapidly that hyperglucemia and glucosuria result. This seems to be 
the explanation of the glucosuria occasioned by Claude Bernard's classical 
experiment of puncture of the medulla and by certain poisons such as 
chloral, morphin, antipyrin, etc. 

General Scheme of Possible Causes of Glucosuria 

1. Alimentary— excessive ingestion of starches or sugars beyond the 
storage capacity of liver and muscles. 

2. Defective hepatic glycogenesis — incapacity of the liver to trans- 
form and store as glycogen. 

3. Excessive hepatic glycolysis — too rapid conversion of glycogen 
into glucose. 

4. Defective muscular glycogenesis — incapacity of the muscles to 
transform sugar and store as glycogen. 

5. Excessive muscular glycolysis — conversion of muscle glycogen 
into sugar and excretion as such. 

6. Inability of the muscles to oxidize sugar. (See Diabetes.) 

7. Increased renal permeability for sugar. (See Diabetes.) 
Clinical Causes of Glucosuria. — Glucose appears in the urine under 

a variety of conditions, including dietary excesses, various infectious 
diseases; intoxications (morphin, strychnin, chloral, acetanilid, etc.); 
concussion, injury and diseases of the central nervous system; after 
convulsions; in thyroid and hypophysis diseases, and in diabetes 
mellitus. 

Diabetes mellitus is a disease in which the carbohydrate metabolism 
is disordered with the result that sugar is excreted in the urine more or 
less continuously. It is probable that the term includes underlying 
pathologic conditions of different sorts all of which however having in 
common the capacity of disturbing the normal consumption of sugar in 
the organism. A mild and a severe form are distinguished, and these 
present some striking differences, to which reference will be made below. 



52 



A TEXT-BOOK OF PATHOLOGY 



Etiology. — Diabetes is frequently a hereditary disease occurring in 
families in which the same disease or obesity and gout have occured. 
The Jews seem particularly liable to it. Overeating, sedentary life, 
and gout are causes of some importance, especially of the milder form. 
Sometimes abnormal conditions of the nervous system may be the 
underlying cause. Among these are functional depressions, as in cases 
of excessive grief; traumatic injuries with concussion of the brain; and 
local diseases at the base of the brain in the vicinity of the medulla. 
Disease of the pancreas is the probable cause in many cases, and probably 
plays a part in all cases, though demonstrable lesions of the pancreas are 
not present in all. Diabetes may occur in the young or after middle life, 
the milder cases more frequently occurring at the latter period. 

Pathogenesis. — In the milder cases of diabetes the same explana- 
tion may be applicable as that given for glucosuria, viz., the liver and 
muscles do not store up the carbohydrates carried to them, and the 
excess of sugar is not burned up in the tissues. Hyperglucemia with 
consequent glucosuria results. In these cases the withdrawal of 
carbohydrate food or temporary abstinence from all food causes 
disappearance of the glucosuria. There is, however, the fundamental 
difference between mere glucosuria and true diabetes that in the former 
the capacity to burn sugar is unimpaired, while in the latter even in 
mild cases this function is more or less disturbed. 

In severe diabetes sugar continues to appear in the urine in spite 
of complete abstinence from starches or sugars. This is explained by 
the conversion of glycogen into sugar and when this supply is exhausted 
by the formation of sugar from the amino-acids of protein catabolism, 
and possibly also by conversion of the glycerol of fat catabolism into 
sugar. In normal individuals, and even in those suffering with mild 
diabetes, any sugar thus liberated is burned in the tissues. Glucosuria 
does not, therefore, occur. Severe and mild diabetes differ only in degree : 
in one case the power to consume sugars is greatly deficient, in the other 
only moderately so. 

The nature of the metabolic disturbances that lead to this inability 
to dispose of carbohydrates is still very obscure. The influence of the 
nervous system is undoubted. Reference may here be made to the occur- 
rence of diabetes after puncture of certain parts of the brain (medulla). 
Very possibly this experiment as well as certain clinical causes of dia- 
betes act by increasing hepatic glycolysis, and in consequence by flooding 
the blood with sugar. Bernard's puncture fails to produce glucosuria in 
animals starved to the extent of depriving the liver of its glycogen. 
Recent investigations suggest that nervous conditions and emotional 
states may stimulate adrenal function and thus occasion glucosuria 
through the action of the adrenal secretion on the liver or pancreas. 

Older pathological studies showed that diseases of the pancreas are 
frequently associated with diabetes, and recent experimental investiga- 
tions emphasize this relationship. Total extirpation of the pancreas 
in the lower animals causes diabetes. The relationship between the 
pancreas and diabetes has not been certainly established. Formerly 
Lepine and others believed that the pancreas elaborates a "glycolytic 
ferment," absence of which in cases of disease of the pancreas would oc- 



DISORDERS OF NUTRITION AND METABOLISM 



53 



casion accumulation of sugar in the blood and consequent glucosuria. 
More recently it has been found that a cooperation of muscle extracts 
with pancreatic extracts is necessary to the destruction of sugar, from 
which it would appear that normally pancreatic secretions are carried 
to the muscles and activate the process of oxidation of sugar. It seems 
to have been established that the final oxidation of sugar occurs in the 
muscles and not in the liver. The secretion of the pancreas involved in 
this function is doubtless a product of the islands of Langerhans. (See 
Pancreas.) Other glands of internal secretion seem to have some relation 
to the pancreas and perhaps to the muscles in the development of dia- 
betes. It is known that epinephrin when injected into the body may 
occasion glucosuria, and diseases of the thyroid gland and the hypophysis 
cerebri also occasion glucosuria. The adrenals and the hypophysis may 
act by restraining normal pancreatic function. 

Renal Glucosuria. — Experimentally, glucosuria may be produced 
by injections of phloridzin, a glucoside which is composed of phloretin 
and glucose. Formally the explanation of- the glucosuria resulting from 
injections of phloridzin was as follows: Splitting of the glucoside into 
glucose and phloretin was supposed to occur in the kidneys, the glucose 
being excreted as such, and the phloretin returning to the circulation and 
reuniting with glucose in the liver or elsewhere to form new phloridzin, 
which underwent the same process as that first administered. Careful 
investigations, however, have shown that phloretin itself does not act 
in this manner, and that the cleavage of phloridzin in the kidney, as 
assumed, is improbable. At the present time the more trustworthy 
explanation of phloridzin glucosuria is that it causes some change in 
renal permeability which occasions active excretion of sugar when the 
sugar concentration of the blood is at or even below the normal level. 
It was early recognized that in cases of phloridzin glucosuria the amount 
of sugar in the blood is not above normal, and this fact was one of the 
confusing conditions that required explanation. In the light of present 
knowledge it would seem that the blood tends to maintain its normal 
sugar content by obtaining glucose from the liver and the diet, while 
the lowered renal threshold allows sugar to escape in the urine. The 
glucose excreted in phloridzinized animals may be derived from proteins 
or fats as well as from the glycogen stores of the body, since it has been 
found that glucosuria occurs in fasting animals presumably deprived of 
all glycogen. 

That the effect of phloridzin is not merely that on renal permeability 
is indicated by the fact that phloridzinized animals excrete quantitatively 
sugars administered in large quantities, showing a loss of sugar burning 
power. 

Is is believed by many that certain cases of glucosuria in man are due to 
a similar disorder of renal permeability, and in particular some cases of glu- 
cosuria associated with gout and arteriosclerosis may be explainable on this 
basis. The occurrence of definite glucosuria without hypergucemia would 
raise the presumption of increased renal permeability (renal diabetes). 
It is impossible at present to make more positive statements. 

The view that diabetes is due to increased formation of sugar has 
been definitely disproved. 



54 



A TEXT-BOOK OF PATHOLOGY 



Metabolism in Diabetes. — The essential metabolic disturbance in 
diabetes is the inability of the body to consume and utilize sugar. In 
mild cases this is a moderately developed defect; in severe diabetes it is 
more and more pronounced, though probably never absolute. As a result 
the sugar concentration of the blood is increased and amounts to from 
0.130 to 0.350 gm. per 100 cubic centimeters. The inability to utilize 
sugar causes increased consumption of fat and proteins and leads to 
emaciation. In mild cases and for a time in severe diabetes overfeeding 
with fats and proteins may prevent loss of weight from destruction of 
the fats and proteins of the body, but eventually this protection of the 
tissues fails to be effective. There is always a tendency to excessive 
destruction of proteins and nitrogens loss, as the diabetic is unable to 
utilize carbohydrates to protect the proteins. The fats also are con- 
sumed to an excessive degree and their oxidation tends to be abnormal, 
as a result of which the ketone acids and acetone are formed in exces- 
sive amounts. (See Acidosis.) Increased elimination of ammonium 
and other bases (alkalies, calcium, magnesium) are expressive of the 
overproduction of acids and their neutralization by the bases in question. 

Pathological Anatomy. — Aside from the lesions already referred to 
as in some way related to the causation of the disease, there are found 
pathological changes of various kinds that result from it. The lesions of 
gout (arteriosclerosis and cirrhotic kidneys) may be of the nature of 
mere concomitants, but similar lesions may be direct results of diabetes. 
Renal diseases are of peculiar interest. Late in diabetes albuminuria 
frequently develops and renal sclerosis may follow. When this occurs 
the glucosuria and other symptoms of diabetes sometimes subside. 
Changes in the liver (cirrhosis) have often been found, and have been 
regarded as causative in some cases. A peculiar form of diabetes with 
hepatic disease and general staining (hemochromatosis) of the skin 
and other tissues has been described under the title diabete bronze. Skin 
eruptions (eczema, furuncles, carbuncles) are frequent in certain forms 
of diabetes, and gangrene of the extremities is common. Pneumonia 
and pulmonary tuberculosis are among the frequent developments of 
late stages of the disease. Chronic endocarditis, neuritis, and cataract 
are not uncommon lesions. 

Pentosuria. — Pentose (a sugar containing five carbon atoms) is found normally 
in the nuclei of cells, the total amount in the whole body being estimated as approxi- 
mately 20 gm. Occasionally pentosuria is met with either in combination with 
glucose in diabetes or as an independent condition unattended by symptoms and 
tending to occur in several members of a family. It is certainly not due to the inges- 
tion of pentoses in the diet, and is probably an independent metabolic disorder 
sometimes associated with diabetes, but at other times wholly independent. 

Oxaluria. — This term is, strictly speaking, applicable only to increase of oxalic 
acid in the urine, but is usually employed for cases in which crystals of oxalate of 
lime are found abundant in the urine. The normal maximum of oxalic acid is 20 
mgr. for twenty-four hours. True oxaluria determined by chemical estimation of 
the total excretion of oxalic acid has been found in jaundice and in some cases of 
diabetes. The source of oxalic acid in the urme is still somewhat in doubt. Several 
investigators claim to have found that the older view regarding its presence in excess 
in the urine following certain kinds of vegetable diet is erroneous, and that there 
is no such thing as "alimentary oxaluria." The weight of opinion, however, still 
favors the older view. There is some experimental evidence for the belief that 



DISORDERS OF NUTRITION AND METABOLISM 



55 



intestinal fermentation is an important factor in the formation of oxalic acid. While 
this may be true, there seems little doubt but that the oxidation of uric acid ac- 
counts for the presence of much of the oxalic acid in the urine, and that nucleins 
and nucleo-albumin are, therefore, important sources of derivation. The authors 
who have argued in favor of a specific disease marked by nervous symptoms and 
oxaluria based their observations on the presence of an excess of oxalate sediment, 
rather than on chemical examinations. Increased sediment occurs in certain in- 
stances of gout in which the oxalates alternate with uric acid or coexist with this. 
In these cases, as in cases of oxalate calculus in the 1 kidney or bladder, the impor- 
tant causative factor is most probably some alteration in the constitution of the 
urine, such as conversion of monosodic phosphate into the disodic phosphate, that 
reduces the solvent power of the urine for oxalate of lime. 

Metabolism of Phosphorus. — Phosphorus exists in the body in the nuclei of cells 
in combination as nucleic acid, in the bones as phosphates, and in the lipoids of 
the nervous system. The phosphorus of food is absorbed as phosphoric acid, which 
combines with sodium, calcium, and magnesium, and from these combinations is 
utilized in the anabolism of phosphatic compounds of the tissues. The excretion of 
phosphorus takes place through the kidneys and intestinal tract. Phosphorus of 
the diet may fail of normal absorption in the presence of excess of calcium, which, 
combining with phosphoric acid, is discharged in the feces. Under ordinary condi- 
tions the phosphorus of the urine, like purin output, is a measure of nucleic metab- 
olism. Excess of phosphorus elimination may be encountered in cases of destruction 
of bone. 

Phosphaturia. — This term should be restricted to increased excretion of phos- 
phoric acid rather than to the presence of increased phosphate sediment in the urine. 
The latter may be due simply to want of acidity of the urine. The daily maximum 
of phosphoric acid with ordinary diet is from 3.5 to 4 gm. The term " phosphaturia" 
might also be applied to cases in which no absolute excess of phosphoric acid is found, 
but in which this substance is relatively in excess when compared with the excretion 
of nitrogen. The normal proportions are from 17 to 20 parts of phosphoric acid 
for 100 parts of nitrogen. Phosphaturia in the sense just described has been found 
in some cases of inanition. Decided increase in the phosphatic excretion, absolute 
as well as relative, occurs in some cases of diabetes; also in cases of tuberculosis and 
disease of the bones, such as ostitis and osteomyelitis. In considering the question of 
phosphatic excretion in the urine it is important to remember that the greatest 
portion of phosphoric acid is derived from the food, only minor quantities coming from 
the metabolic consumption of tissues. Further, it must be remembered that much of 
the phosphoric acid of metabolism is excreted through the bowel. Recent observa- 
tions show that when there is some intestinal disorder preventing excretion of calcium 
from the intestines there may be excess of phosphoric excretion in the urine in combi- 
nation with calcium. The term diabetes phosphaticus has been used by Tiessier for 
phosphaturia in the sense of increased total excretion, and four varieties have been 
described; (a) cases with polyuria and marked nervous symptoms; (b) cases preceding 
or accompanying pulmonary diseases, especially tuberculosis; (cj cases in which phos- 
phaturia alternates with or coexists with glycosuria; and {d) cases in which oxaluria, 
polyuria, and slight albuminuria are present and in which there is some relationship 
with gout. 

The nature of the metabolic disturbances in phosphaturia are obscure. Some- 
times the disorder of metabolism seems to be merely quantitative; in other cases, 
doubtless qualitative. 

FEVER 

Definition. — It is not easy to define this term accurately, though 
we may regard as fever a condition in which the temperature of the 
body is elevated above the normal (98.4° F.; 37° C.) and in which the 
tissue-metabolism is altered in the direction of increased consumption. 
There are cases in which the latter is insignificant or wanting, and there 
are other instances in which the temperature remains normal or sub- 
normal under influences that ordinarily provoke fever. It is doubtful 



56 



A TEXT-BOOK OF PATHOLOGY 



whether mere elevation of temperature, such as occurs in experimental 
injury of certain parts of the brain, constitutes fever; but unquestionably 
it would be improper to apply this term to conditions of excessive tissue 
destruction without elevation of temperature. 

Nature. — It is important, first, to consider the regulation of the 
temperature in health. In the normal individual heat is produced in the 
body by constant oxidation and other metabolic activities, and the 
excess is dissipated by radiation from the surface and the heating or 
evaporation of excreta. These processes of heat production and heat 
dissipation are regulated in an orderly manner under the influence of the 
nervous system. Special centers for the production, dissipation, and 
regulation of heat have been described by the physiologists, though 
their location and method of operation still remain in doubt. What- 
ever the exact mechanism may be, it is quite certain that in some way 
the nervous system exercises a control over production and discharge 
of heat. 

The excessive heat of fever -may conceivably be due to excess of 
heat production, to diminution of the dissipation, to both of these con- 
ditions, or to increase of both with greater excess of production. In 
most instances of fever in man it appears that production and dissipa- 
tion are both increased, though the latter is insufficient. At the onset 
heat dissipation may for a time be diminished. The increased produc- 
tion results from increased, oxidation and other metabolic processes. 
A study of the respiratory exchange of gases shows that oxygen is con- 
sumed in greater quantity than normally, and the quantity of CQ2 
is correspondingly increased. The excess may amount to as much as 20 
per cent., but in part this increased oxidation is due to the stimulation 
of muscular contractions in rigor, etc. Investigation of the excreta 
shows at the same time evidences of more or less rapid and extensive 
tissue waste. The quantity of nitrogen eliminated is in excess of that 
consumed in the food, and wasting of the tissues results. The albu- 
minous elements suffer particularly in the metabolic wasting, the de- 
crease of fat being more especially dependent on insufficiency of food. 

Etiology. — Tha causes of fever doubtless vary greatly. Direct 
exposure to heat does not affect the temperature more than a fraction 
of a degree in healthy persons, unless the surrounding temperature 
is very great. Ordinarily the heat-regulating mechanism maintains a 
proper adjustment. Excessive heat may, however, bring on fever, as 
in the case of sunstroke. Here, it has been held that the heat leads to 
direct disturbances of the regulating apparatus in the central nervous 
system; but recent investigations seem to show that there are first 
produced toxic substances which secondarily influence the heat-centers 
of the brain. In another class of cases still more direct disturbance of 
heat regulation seems to occasion fever. Among these cases are the in- 
stances of fever in hysteria and other nervous diseases. 

In the great majority of cases of fever it is quite certain that toxic 
substances are the cause of the febrile disturbances. These substances 
may be of quite different sorts. In the case of infections it is known that 
certain substances contained within the bacteria themselves may cause 
fever, and that products of the growth of the micro-organisms may have 



DISORDERS OF NUTRITION AND METABOLISM 



57 



the same effect. These substances are probably of albuminous nature. 
Other albuminous bodies resulting from normal or disturbed metabo- 
lism, independent of the action of bacteria, such as albumoses, peptone, 
tissue-fibrinogen, etc., may be equally potent; and various ferments, 
such as pepsin, fibrin-ferment, diastase, etc., are known to have the same 
power. These facts explain the multiplicity of causes capable of produc- 
ing fever, as any chemical, mechanical, or bacterial injury of the tissues 
may liberate toxic substances, which in turn act upon the nervous sys- 
tem and occasion the phenomena of fever. 

Pathological Physiology. — Fever is accompanied by or leads to a 
variety of disorders. The appetite is lost, there is excessive thirst, 
emaciation is habitual, and the functions of the various organs are more 
or less disturbed. To a large extent these results are doubtless due to 
the presence of toxic substances in the blood and to other changes in this 
fluid. This is usually chlorid retention and, despite the increased elimina- 
tion through the skin and lungs, retention of water, so that loss of weight 
may not be as evident as the amount of tissue destruction would other- 
wise occasion. A common and possibly characteristic metabolic proc- 
ess is the hydration of the albuminous tissues with formation of 
albumoses. There is little accurate knowledge of the toxic substances in 
the blood. The original posions that caused the fever may be toxic for 
the entire organism, and other poisons may be produced by the elevation 
of temperature and the disturbed metabolism. 

Pathological Anatomy. — Definite morbid changes may occur in the 
various tissues of the body, notably the muscles, heart, liver, and kidneys. 
Among the changes are cloudy swelling, fatty degeneration, and coagula- 
tion necrosis. It is unlikely that these changes are the direct result of the 
increased temperature. More probably they result from the action of 
toxic substances. 

Conservative Effects of Fever. — 'While fever occasions many dis- 
turbances and leads to various pathological consequences, it is not im- 
probable that it manifests conservation effects. Some authors have 
called attention to the fact that rapid reduction of the temperature 
under the influence of antipyretics is often followed by harmful conse- 
quences. This does not necessarily prove the usefulness of the fever, 
as the antipyretics are often capable of harm in themselves. A more 
definite proof of the uses of fever is that obtained by subjecting infected 
animals to high temperature or to febrile conditions, and then studying 
the progress of the infection. Under these circumstances it has been 
found that the course of various infections, such as with the Diplococcus 
pneumoniae, the bacillus of typhoid fever, and other organisms, is much 
milder and the consequences less serious than in animals not placed under 
the same conditions. These results agree very well with experiments with 
bacteria outside the animal body. For example, it is known that many of 
the bacteria are influenced unfavorably in their growth and virulence by 
excessive temperatures (104° to 107.6° F. ; 40° to 42° C.) . Whether in the 
body the temperature affects the micro-organisms directly or indirectly 
through the production of antitoxic substances, or in other ways, remains 
unsettled. It is not unlikely that increased circulation and respiration 
favor the elimination of the toxins that cause the fever. Increased toxicity 



58 



A TEXT-BOOK OF PATHOLOGY 



of the urine has been found, but the methods employed are open to 
criticism. 

BERIBERI 

Definition. — Beriberi, or kakke, is an epidemic or endemic specific 
polyneuritis, with alterations of sensation and motility, and associated 
disturbances of digestion. This disease was long regarded as an infec- 
tion, and in some particulars strongly suggests one but it is not com- 
municable. It occurs in tropical and subtropical countries, and is 
characterized by muscular weakness, generalized muscle pains, dropsy 
and cardiac failure. 

Etiology. — Beriberi occurs among young persons and usually affects 
numbers of people. It is most frequent along ocean coasts and great 
rivers, and is most prevalent during damp seasons of the year. Dietary 
conditions, such as may arise from defective food on ships and in institu- 
tions, appear important in its etiology. 

The cause of beriberi is unknown; no virus has been isolated to 
establish its infective nature, and it is now believed to belong to the so- 
called deficiency diseases wherein some necessary food element is absent 
from the discharge. The use of decorticated rice seems to be the prin- 
cipal factor in the causation of the disease. In milling and polishing rice 
the pericarp, rich in valuable phosphorus, is removed. Much informa- 
tion has been gleaned by the experimental production of a degeneration 
peripheral neuritis in birds by feeding with such polished rice, and a 
similar experiment has been made with condemned prisoners. The im- 
portance of the unknown substance in the covering of the rice grain is 
shown by the fact that improvement follows the use of rice-bran in beri- 
beri and experimental polyneuritis. This substance is either necessary 
to nutrition, or its absence disturbs metabolism in the nervous tissues. 
Some observers believe toxins are formed by cooking improperly pre- 
served or spoiled rice. Moszkowksi produced beriberi in himself by a 
diet of polished rice. His symptoms indicated no change in the motor 
nerves, the sensory only being affected, and the reflexes were increased. 
There was excessive nitrogen excretion, but the phosphorus metabolism 
seemed normal. The disease may be transmitted to the young through 
the milk. The form chiefly associated with superficial dropsies is called 
" kakke," believed by some to be an independent disease. This is denied 
by others. 

The sensory phenomena take the form of areas of reduced tactile 
sense and are commonly met upon the dorsum of the foot, finger-tips 
and dorsum of the hand, around the mouth, and upon the abdomen. 
Edema of the superficial parts may or may not be seen. Then follow 
palsies of the dorsal muscles of leg and hand, and at times of the cranial 
nerves supplying face and neck. Death occurs by exhaustion or inter- 
current infections. The pathology, except in the nervous system, is in 
no way specific. There is a slight anemia and leukocytosis. Edema in 
several isolated areas may be found. Congestions and early inflamma- 
tions are common. This is particularly true of the gastro-intestinal 
tract, where the mucosa is cyanotic, but the glands are little if any 
changed. Parenchymatous degenerations are met. In the peripheral 



DISORDERS OF NUTRITION AND METABOLISM 



59 



nerves there is degenerative neuritis with increase of nuclei, probably 
from the sheath of Schwann. The ganglia on the posterior roots and 
occasionally the roots themselves are degenerated. 

PELLAGRA 

This is a chronic, relapsing, non-febrile disease characterized by a 
more or less specific cutaneous eruption and nervous and digestive dis- 
turbances. Its etiology is not certainly known, but it has been supposed 
to be due to the use as food of Indian corn in which a toxin has arisen 
by infestation with certain aspergillus species. This is in accord with 
its appearance in the spring and summer. Various bacilli and amebse 
have been considered causes of pellagra, and lately Sambon asserts that 
it is transmitted by an insect. Late observations indicate that it may 
be transmitted to monkeys by Berkefeld filtrates from tissues of human 
cases. It occurs most commonly in white females between twenty and 
forty, beginning in May and June. Poor environment and living con- 
ditions favor its development. 

The cutaneous manifestations take the form of an erythematous 
dermatitis on exposed parts, which are aggravated by exposure to sun- 
light. The skin may swell or vesicles may form. The distribution is 
apt to be symmetrical and the patches limited. Thickening of the super- 
ficial layers, with pigmentation and parchment-like appearance, is the 
common condition in later stages. 

The nervous conditions comprise anesthesias, paresthesias, early 
increase of reflexes, and tremors. Later, evidences of dementia set in. 

There is no specific pathology. There are congestion and pigmenta- 
tion, and sometimes fatty degeneration of parenchymatous organs. 
Ulcers in the colon may be found. In the nervous system meningitis 
of a low order, degeneration of a few nerve- and ganglion cells, perivas- 
cular infiltration of round cells and degeneration of the posterior and 
lateral columns have been reported. The cerebrospinal fluid is usually 
abundant, possibly under pressure, limpid, clear, sterile, and contains 
some increase in protein and lymphocytes. 

There seems to be a lowered and somewhat perverted protein metab- 
olism in pellagra. Judging from the known facts that hyperacidity 
exists in the stomach, we may assume that digestion is deficient in the 
intestine. 

The microscopical changes in the skin are degeneration in the corium, 
followed by mild granulation tissue and thickening accompanied by 
proliferation in the spinous and granular epithelium in which pigment 
is prominent. 

The last two diseases, beriberi and pellagra, seem to be due to the 
absence from the diet of substances necessary to the construction of the 
phosphatids of nervous tissue, to which Funk has given the name "vit- 
amins." Their exact nature is not yet clear, but they do not seem to be 
proteins or carbohydrates. 



CHAPTER III 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 

GENERAL DISTURBANCES 

The circulation of the blood is maintained by the rhythmic con- 
tractions of the auricles and ventricles of the heart, aided by the elas- 
ticity of the arteries; by the compression of the veins by the muscles; 
and by the suction of the inspiratory movements of the chest. 

General disturbances of the circulation result from lessened or 
excessive heart power, from arterial disturbances, or from changes 
in the quantity or character of the blood. Muscular and respiratory 
weakness may be contributing causes. 

Weak Heart.- — There are various forms of heart disease that may 
lead to disordered circulation. The muscle itself may be weakened from 
overstrain, the fevers or other diseases, the action of poisons or insuf- 
ficient nourishment, as in the anemias or from narrowing of the coro- 
nary artery. The muscle may be soft and cloudy, fatty, or hardened by 
sclerotic changes. There may be no evident muscular disease, but 
merely functional weakness. The valves or orifices of the heart may 
be diseased, and regurgitation or obstruction of the blood-flow results. 
Sometimes blood-clots form within the heart and similarly cause ob- 
struction of the current. Finally, pericardial effusion or adhesions or 
tumors pressing upon the heart may serously disturb its action. 

The result of the weakened state of the heart must be the accumula- 
tion of blood in the venous system. The place of engorgement depends 
upon the part of the heart specially weakened. If the left ventricle 
fails, the blood backs into the left auricle and the lungs. As long as the 
right heart maintains its power the venous congestion goes no further; 
but when this fails, overfilling of the right auricle and of the systemic 
veins ensues. When the right heart is first at fault, general venous con- 
gestion is an earlier manifestation. In all cases the arterial pressure falls 
and the blood-current is slowed, whereas the venous pressure is increased. 

Sudden and complete failure of the heart causes anemia of the brain 
and syncope, which may prove fatal if not instantly relieved. 

Hypostatic Congestion. — In cases of serious weakness of the heart, 
in which it is quite unable to maintain an active circulation, the blood 
tends by the force of gravity to sink to dependent parts. This condi- 
tion is known as hypostatic congestion. It occurs very frequently in 
low fevers and quite commonly just before slow death resulting from 
any cause. Dilatation of the vessels from vasomotor paresis, general 
muscular weakness, and the failure of vigorous inspiratory efforts are 
secondary causes. 

60 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 61 

The blood accumulates in the skin of the back, especially about 
the buttocks. The skin is of a livid color, but is bloodless over the 
bony points; the tissues tend to become sodden from transudation of 
liquid from the blood-vessels. Sloughing and gangrene (bed-sores) 
may result. Internally, hypostatic congestion affects the lungs par- 
ticularly, and a form of pneumonia may follow. 

Postmorten lividity is allied to hypostatic congestion. After death 
the blood gravitates to the dependent parts and accumulates in the 
veins, as the arteries contract when the heart-action ceases. 

Overaction of the heart is less frequent than weakness. Tem- 
porary overaction occasions increased activity of the circulation and 
elevation of blood-pressure, sometimes sufficient to cause hemorrhage. 
More prolonged overaction due to overwork, to excessive feeding, or to 
nervous stimulation, as in Graves' disease, causes hypertrophy of the 
left ventricle, and later of the whole organ. In consequence the circu- 
lation may be more or less permanently overactive. 

Arterial Disorders. — Both organic and vasomotor disturbances are 
important. Of the organic disturbances the most frequent is sclerosis of 
the arteries, which offers a constant impediment to the arterial circula- 
tion. Hypertrophy of the heart overcomes the obstacle, but when the 
heart fails venous congestion and dropsy ensue. Sclerosis may also 
affect the veins, but much less commonly. Local diseases of the aorta, 
as congenital narrowing, compression by enlarged glands or tumors, 
aneurysms, and blood-clots may obstruct the flow of blood to the arteries, 
and thereby cause stagnation of the blood in the heart, lungs, and venous 
system. 

Vasomotor disturbances are dependent upon the nervous system. 
Under the influence of certain diseases of the nervous system or of 
poisons (as carbonic acid gas in asphyxia) acting locally on the vessels 
or upon the vasomotor center in the brain, . contraction of the smaller 
arterioles occurs; and in consequence the blood-pressure is greatly 
elevated, the heart is impeded, and venous congestion results. On the 
other hand, the arterioles may distend from vasomotor paresis, the 
blood-pressure falls, and unless the heart is active there is a tendency to 
hypostatic congestion. 

Changes in the Blood. — 'Increase and decrease of the quantity of the 
blood are generally merely passing conditions to which the circulation 
readily adapts itself by dilatation or contraction of the vessels. Sudden 
losses of blood, if large, may be fatal by syncope. Smaller losses are soon 
repaired by absorption of water from the tissues and by regeneration of 
blood. Increase in the quantity of the blood by ingestion of liquids 
never disturbs the circulation greatly. Rapid excretion soon reduces 
the quantity to the normal. 

Changes in the character of the blood may affect its circulation. 
The accumulation of carbonic acid and probably other effete products 
of tissue change impede the flow by exciting vasomotor contraction. 
This is probably brought about by the action of poisons on the 
terminal nerve-filaments in the blood-vessels or directly on the walls of 
the vessels. This is the best explanation of the increase of pressure in 
cases of Bright's disease without arteriosclerosis. The poisons in this 



62 



A TEXT-BOOK OF PATHOLOGY 



case are quite possibly retained substances which the damaged kidney 
cannot excrete. 

The changes in pressure cited above may be largely due to changes 
in the viscosity of the blood. In general, anything which increases the 
cellular content or molecular concentration increases pressure, while the 
reverse is naturally the case. The chromaffin system, particularly of 
the adrenals, seems to have a stimulating effect upon blood-pressure. 
It is believed by some observers that an overproduction of epinephrin 
is responsible for chronic arterial disease. 

Concerning the muscular and respiratory influence upon the circula- 
tion, it is to be remembered that contraction of muscles has a decided 
propelling action upon the blood current and that the difference in 
intrathoracic pressure during inspiration and expiration is a great aid in 
fining the large vessels of the chest. When therefore muscular power 
is decreased venous return is deficient, and when excessive, blood pressure 
is heightened. Respiratory hmitation as in asthma or pleural exudates, 
with the establishment of a positive intrathoracic pressure, impedes the 
fining of the right heart and aeration of the blood. 



LOCAL ANEMIA 



Local anemia or ischemia is the condition in which a tissue contains 
less than its proper quantity of blood. This may be direct when it results 
from causes obstructing the flow into arteries, 
or collateral when it is due to withdrawal of 
blood into hyperemic areas in other parts of the 
body. Of the causes acting directly, pressure 
is the most frequent. There may be general 
pressure upon an organ or localized area of the 
body, as in the application of elastic bandages; 
or pressure upon the vessels within the tissue 
itself, as in amyloid disease, the amyloid sub- 
stance compressing the arteries and capillaries, 
or there may be direct compression of an artery 
by tumors. The circulation in an artery may 
be impeded by sclerosis of the vessel walls and 
by emboli or thrombi within the vessel. Local 
anemia of moderate or even severe grade may 
be due to nervous influences acting through the 
vasomotor system, as in the earlier manifesta- 
tions of Raynaud's disease. Collateral anemia 
is well illustrated by the anemia of the brain 
occurring in animals in which the splanchnic 
nerves have been cut, with the consequent pro- 
duction of abdominal hyperemia. When ischemia is due to obstruction 
of a single vessel the circulation is generally soon restored by collateral 
anastomosis; the collateral vessels sometimes reach considerable dimen- 
sions (Fig. 1). When an artery which has few anastomoses and which 
soon splits up into capillaries is obstructed, the phenomena of infarction 
(see page 70) ensue. 




Fig. 1. — Anastomoses 
three months after ligation 
of the femoral artery of a 
dog (Porta). 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 63 

An anemic area is pale, reduced in size and temperature, and func- 
tionally less active than normal. If the condition persists, fatty de- 
generation and necrosis results, a condition probably due largely to the 
deprivation of oxygen and the liberation of autolytic ferments; the 
changes are best seen in infarction. When a severe local anemia is 
relieved it is apt to be followed by hyperemia of the same area, due to 
exhaustion or degenerative weakness of the vessel walls. 

LOCAL HYPEREMIA 

Local hyperemia is increase in the quantity of blood in a part of the 
body. This may be due to increase of the flow to that part, or to ob- 
struction of the outflow. The former is called active or arterial hyperemia 
or congestion; the latter, passive or venous hyperemia. 

Active hyperemia occurs in organs during periods of functional 
activity, the increased blood-supply here being due to increased demand 
for nutrition. Pathologically, active hyperemia is due to causes which 
lead to dilatation of the arteries of a certain part. This dilatation may 
be due to influences acting through the vasomotor nervous system or to 
local affections of the vessel walls. The vasomotor nervous system may 
be affected at its center in the medulla or peripherally. The latter is 
seen when the sympathetic nerves, which contain vasoconstrictor fibers, 
are severed or compressed by tumors, the vessel walls thereby becoming 
paralyzed (neuroparalytic hyperemia). The superficial congestive hy- 
peremia in fevers is probably due to the central vasomotor action of the 
toxic causes of fever. On the other hand, the vasodilator fibers in the 
spinal nerves may be stimulated, as in certain cases of neuritis, with 
a similar result (neurotonic hyperemia). Direct injury to the vessel 
walls by heat, traumatism, inflammation, chemicals, or by the vascular 
fatigue following temporary stoppage of the circulation is a frequent 
cause. Active hyperemia is spoken of as collateral when anemia in one 
part leads to overfilling of the vessels of an adjoining or even distant part. 

The hyperemic area is bright red in color, the temperature is ele- 
vated, and there is slight swelling, due to the increase of blood in the 
part and transudation of serum into the tissues. After death the dis- 
tended arteries and capillaries may contract and the part grows paler. 
Arterial hyperemia is one of the phenomena of beginning inflamma- 
tion, and in any case if prolonged may terminate in inflammation. 
Functional activity is increased by moderate congestions. 

Passive hyperemia is due to impediments to the outflow of the 
blood through the veins. This may be brought about by compression 
of veins by tumors, by thickening of their walls, by thrombi within, 
or in the case of the lungs and great veins of the trunk by obstruction 
in the right heart from valvular thickening or incompetency. Little 
disturbance results from obstruction of a small vein, because of the 
freedom of collateral circulation, provided the heart is active. In 
cases of weak heart-power, however, slight obstructions may determine 
local venous hyperemia, or by gravity alone the blood may accumulate in 
dependent parts. The latter constitutes hypostatic congestion. 

When venous channels have been obstructed for more than a short 
time, nature makes an attempt to return the blood to the heart, by 



64 



A TEXT-BOOK OF PATHOLOGY 



. ii 



establishing collateral circulation or enlarging existing anastamoses. 
Thus in portal cirrhosis the stasis in the intraabdominal veins leads to a 
dilatation of the parietal and cutaneous vessels draining to the thoracic 
and femoral regions. 

Areas the seat of passive hyperemia are dark red or bluish (cyanosis) 
and lowered in temperature. The veins are distended, and very soon the 
watery elements of the blood transude and the part becomes edematous 
and swollen. In severe cases red blood-corpuscles escape by diapedesis. 

The appearance of blue discoloration in congested parts has been laid 
to the lowered volume of oxygen and increased amount of reduced hemo- 
globin, due either to transfer of the former to the tissues and the taking 
over by the blood of metabolic products and C0 2 during stasis, or by 
imperfect oxygenation of the blood in the lungs, which can occur when 

atmospheric oxygen is low in tension or pul- 

• . monary aeration is defective (cardiac decom- 

- - pensatiori). 

In consequence of the increased intravas- 
cular pressure the red corpuscles are pushed 
through the wall of the vessel at the angular 
junction of adjacent endothelial cells. At 
these points the cement substance is found in 
greater abundance than along the borders of 
the cells, and the escape of the corpuscle takes 
place through the semisolid cement substance. 

Later fatty degeneration results from the 
imperfect nutrition of the tissues; or even 
necrosis and gangrene may occur. In long- 
continued moderate passive hyperemia over- 
growth of connective tissue, due either to 
direct irritation or to replace the atrophied 
parenchyma or both, and pigmentation of the 
tissue by broken-down blood-corpuscles are 
observed (brown induration). 

Complete stoppage of the circulation in a 
localized area is called stasis (Fig. 2). This 
may be an extreme grade of passive hyperemia. 
The blood-corpuscles accumulate in the small vessels (arteries, capillaries, 
and veins), and the plasma is slowly pressed through the vessel wall or 
onward in the vessel. There results a filling of the vessel with a homo- 
geneous red material, which is composed of the red corpuscles so closely 
packed as to be indistinguishable. On relief of the stasis the corpuscles 
become free again. Stasis may also be produced by chemical agents 
which rapidly withdraw the plasma from the vessels, leaving the corpuscles 
unable to circulate; or similarly by rapid evaporation of the liquor 
sanguinis from internal structures (as the peritoneum) exposed to the air. 

Passive congestion of any grade and stasis interfere with functional 
activity in two ways: by the reduction of nutrition of the cells and by 
the pressure exercised upon them by the accumulating blood and serum. 
These areas are at first protected against infection because of the excess 
of venous blood, which has a high restraining power upon germs. 




Fig. 2. — Stasis of blood in 
the superficial vessels in a 
case of valvular disease and 
heart failure (modified from 
Ziegler) . 



DISTURBANCES OF THE CIRCULATION OE THE BLOOD 



65 



HEMORRHAGE 

By hemorrhage is meant the escape of the several constituents of 
the blood from the blood-vessels. It is said to be arterial, venous, or capil- 
lary, according to the vessel from which the flow of blood takes place, 
and parenchymatous when it comes from all of the vessels. Hemorrhage 
may occur either by diapedesis and extravasation through intact vessels 
{hemorrhage per diapedesin) or by actual rupture of a vessel {hemorrhage 
per rhexin) . The former process is seen only in the capillaries and smaller 
veins; the latter occurs mainly in the arteries and veins. 

Emigration and Diapedesis. — Under normal conditions a certain 
number of white corpuscles, by virtue of their ameboid movements, 
escape from the capillaries, and become wandering cells which move 
about in the tissues or are carried by the lymph-stream. This process is 
called emigration. There is at the same time some transudation of 
plasma, which, with the leukocytes, enters^ the lymphatic circulation. 
Under certain abnormal conditions the red corpuscles also pass through 
the vessel wall and collect in the tissues. This is known as diapedesis 




Fig. 3. — Diapedesis of the red. blood-corpuscles through a capillary of a frog's tongue 

(after Thoma). 

(Fig. 3). It may be studied very readily under the microscope in the 
mesentery of a living frog. It is noticed that the red corpuscles approach 
certain parts of the wall of the capillary or vein and become fixed; then 
a small projection appears outside the vessel, opposite the corpuscle, 
and as this increases the corpuscle within grows smaller, until the whole 
body had gradually passed through. Not rarely several corpuscles pass 
through in one mass, as has been particularly noted by Thoma. Out- 
side the vessel the corpuscle at once assumes its ordinary shape. 

Diapedesis was first studied by Strieker and Cohnheim. Arnold, whose investi- 
gations are most important, first believed that the emergence of the red corpuscles 
takes place through orifices or stomata; but later recognized, as is now generally 
believed, that the supposed stomata are merely accumulations of intercellular sub- 
stance in certain places between adjoining endothelial cells or at the junction of 
several cells. The active cause of the extrusion of the red corpuscles is the pressure 
of the blood. It has been thought that chemical changes in the endothelial cells or 
the so-called stomata must precede the diapedesis. 
5 



66 



A TEXT-BOOK OF PATHOLOGY 



The leukocytes emigrate from the vessel in exactly the same way 
as the red corpuscles, but mainly by their own ameboid movements. 
At the same time there is a more or less copious overflow of plasma. 

Diapedesis is readily induced by mechanical compression of a vein, 
which elevates the blood-pressure; or it may follow elevation of blood- 
pressure from any other cause. On the other hand, with normal pres- 
sure increased permeability of the vessel walls may occasion diapedesis. 
Such degenerative conditions of the vessels may be due to the action of 
poisons, to various infectious diseases, to moderate traumatism, or to 
temporary obstruction to the flow of blood into a certain area. Perhaps 
also altered states of the blood may play a part when both the vessels 
and pressure are normal. Hemorrhages by diapedesis are generally 
small and punctate (petechial), but may be quite large, as sometimes in 
the conjunctiva. 

The solution of the endothelia or the intercellular cement substance 
may be caused by many toxins, and seems not to be dependent on any 
one chemical substance, but is expressed by many bacterial and other 
toxins such as those from snakes and plants. This change in the lining 
cells seems also to have occurred, probably by malnutrition, in vessels 
though which the circulation has been suspended for a time, because after 
resumption of the flow more or less extensive extravasation may occur 
from- such vessels. 

Multiple ecchymoses may result from obstruction of capillaries or 
small blood-vessels. Such obstructions occur in the form of hyaline 
thrombi in various infections, as a result of burns or freezing of the skin, 
as well as from exogenous and endogenous poisoning. Fat embolism and 
embolism of parenchymatous cells may bring about the same result. 

Causes of Hemorrhage. — The ordinary form of hemorrhage per 
rhexin may be due to traumatism, to diseases of the vessels, to increase 
of the blood-pressure, and to certain vague nervous influences. 

1. Traumatic hemorrhage may be due to direct laceration of a vessel 
or to contusions which merely weaken the vessel wall and lead to sub- 
sequent rupture. 

2. Diseases of the blood-vessels causing hemorrhage generally 
originate from causes within the vessel, and are due to such conditions 
as poisoning, infections, cachexias, or the anemias. Among the diseases 
of the vessels are fatty degeneration of the intima or media, atheroma, 
and miliary aneurysm. On the other hand, the outer coat may be eroded 
by surrounding disease and hemorrhage ensues (hemorrhage per dia- 
brosin). This is seen in phthisic cavities in the lungs. 

3. Increase of blood-pressure may be absolute or relative. The 
former occurs from emotional excitement, from hypertrophy of the heart, 
during paroxysms of whooping-cough, croup, and various convulsive 
disorders. In asphyxia there is decided increase of blood-pressure both 
from vasomotor contraction and from the violent muscular efforts. 
Relative increase of pressure occurs when the pressure external to the 
vessel is reduced, as in balloon ascensions, or in the pleura in cases in 
which during violent inspiratory efforts the air cannot enter the lungs, 
as in the fetus attempting to breathe during labor. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



67 



4. Neuropathic Hemorrhage. — The nervous system exercises a pe- 
culiar influence upon the vessels. In cases of apoplexy, of epilepsy, and 
of section of the spinal cord and in other nervous conditions spontaneous 
hemorrhages from the nose or stomach, or into the lungs, suprarenal 
bodies, and other organs, are not infrequent. In the same group also 
are to be reckoned the instances of vicarious hemorrhage due to suppres- 
sion of the menses and the remarkable cases of stigmatization. The 
last named is a condition in which under nervous exaltation or hysteria 
spontaneous hemorrhages occur from various parts of the body, especially 
from the parts wounded in the Crucifixion. 




Fig. 4. — Fat embolism in the glomerular capillaries of the kidneys in a case of severe 
comminuted fracture. Stained by osmic acid. 

5. The Hemorrhagic Diathesis. — Certain persons present an in- 
herited tendency to bleed spontaneously or after very trivial injuries. 
Such persons are known as bleeders/' and the condition as hemophilia. 
The exact pathological condition which occasions the hemorrhages is still 
uncertain, nor are their any peculiar anatomical changes in the body. 
All that can be stated today with reasonable certainty is that there is a 
deficiency of prothrombin in the blood plasma, and that the platelets, 
while about normal in number, are unable to perform their usual part 
in the process of coagulation. Hemophilia is a familial disease mani- 
fested by extraordinary tendency to bleed either spontaneously or upon 
trivial injury. The hemorrhage may be external, submembranous, or 
interstitial. The diathesis is transmitted by the females and expressed 
by the males. The reverse has been known to occur. There is a lower 



68 



A TEXT-BOOK OF PATHOLOGY 



coagulability of the blood, a prolongation of the clotting time, and prob- 
ably a lowered tonicity of vessel walls. Rudolph and Cole cite two cases 
in which the clotting times were nine and one-half and nineteen minutes. 

A hemorrhagic diathesis may also be developed as a result of various 
diseases, as typhus fever, anthrax, septicemia, or phosphorus-poisoning. 
The same is observed in the severe forms of anemia, like progressive 
pernicious anemia and leukemia. In these cases altered blood states and 
disease of the vessel walls are doubtless the causes at work. 

Classification of Hemorrhages. — Hemorrhage may occur on free 
surfaces or into the tissues. In the former case various names are ap- 
plied to designate the locality, such as epistaxis, nosebleed; hemoptysis 
hemorrhage from the lungs; hematemesis, from the stomach; enter -or- 
rhagia from the bowel; metorrhagia, uterine hemorrhage between, and 
menorrhagia, at the menses. 

Hemorrhages into the tissues take their names from the size and 
nature of the lesion. A hemorrhagic infiltration beneath a surface, as 
of the skin or mucous membrane, is called an ecchymosis, which if small 
and well defined is a petechia, but if large and diffuse, a suggillation or 
suffusion. A distinct accumulation of blood, constituting a veritable 
blood-tumor, is known as a hematoma. Infiltrations of a peculiar sort, 
involving localized portions of a tissue or organ, are known as hemor- 
rhagic infarcts (q. v.). 

Results of Hemorrhage. — A very large hemorrhage may cause 
sudden death by cerebral anemia. More frequently the patient remains 
in shock for a time and then slowly recovers. The hemorrhage ceases 
spontaneoulsy by the diminution in heart action, by clotting of the blood 
at the point of rupture, by retraction of the elastic vessels, and by pres- 
sure of the surrounding tissues. Blood extravasated in the tissues 
soon coagulates and subsequently undergoes disorganization, the red 
corpuscles breaking down into pigment matter, hematoidin and hemo- 
siderin, which may be carried away or deposited at the seat of hemor- 
rhage, causing the well known black and blue mark. The fluid elements 
may be completely absorbed, or, stained with coloring-matter, may re- 
main as a cyst in which cholesterol plates are usually found. The solution 
of a large blood collection is due to leukocytic enzymes and products of 
tissue cell destruction. A focus of hemorrhage may set up reactive 
inflammation and lead to encapsulation by new connective tissue. Some- 
times hemorrhagic accumulations become inspissated and undergo calci- 
fication. Blood in the serous sacs does not readily coagulate, but mingles 
with the normal liquid secretion. It may be gradually absorbed or may 
undergo degenerative changes, especially when infected by micro-organ- 
isms. Large hemorrhages cause acute anemia; repeated small extrava- 
sations may lead to profound secondary anemia. (These conditions 
will be more fully discussed under Diseases of the Blood.) 

EMBOLISM 

Embolism is the process in which foreign bodies of various kinds 
are carried in the blood and deposited in the smaller arteries or capil- 
laries through which their size does not permit them to pass. The 
bodies deposited are called emboli. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



69 



Sources and Nature of Emboli. — The most common form of em- 
bolism is that in which portions of thrombi situated in the heart, the 
large veins of the extremeties or pelvis, or on atheromatous patches in 
the aorta, are swept into the circulation and lodge in the smaller vessels. 
Softening of the original thrombus is generally the immediate cause. 
More rarely portions of a diseased heart-valve or of the intima of the- 
heart or arteries, liver or placental cells, or parts of tumors are carried 
in the circulation and deposited as emboli. Embolism of large giant 
cells of the bone-marrow is common. Disorganization of the blood 
may cause embolism of pigment particles, as in malaria, or of small hyaline 
masses, as in burns and certain forms of poisoning. In cases of fracture 
of bones particles of fat may be dislodged from the marrow and enter the 
circulation, while in wounds of the large veins of the neck or elsewhere 
air-embolism is observed. Finally, masses of bacteria, scolices of echi- 
nococcus, and other parasites are serious forms of emboli. 

Dust-embolism. — Small particles of coal, iron, marble, or clay entering the lungs 
in respiration sometimes penetrate the tissues, are largely taken up by phagocytic 
cells, and for the most part are carried to the bronchial lymphatic glands. If the 
latter are surcharged and soften, the dust particles may gain access to the circulation 
through the efferent lymph-channels of the gland or by rupture of the gland into» 
neighboring veins. More rarely dust particles may enter the blood-vessels in the 
lungs directly by penetration. After their entrance into the blood they are depos- 
ited in the capillaries and substance of the liver, spleen, and bone-marrow, where they 
may remain permanently, either free or enclosed in fixed cells, or whence they may be 
removed by wandering cells. The final discharge occurs especially from the lungs,, 
the tonsils, the lymphatic structures of the intestines, and from the liver in the bile. 

Air-embolism. — Small quantities of air may occasion no serious disturbances; 
but when large quantities enter the veins the right heart is found full of frothy blood 
and the pulmonary arterioles are occluded by small bubbles. Sudden death in these 
cases is not unusual. Some experiments in dogs seem to cast doubt on the serious- 
ness of air-embolism, but the matter is not yet settled. (See Caisson Disease.) 

Fat-embolism. — Sudden death may occur when a large number of the pulmon- 
ary vessels are obstructed by embolic oil-drops. When the process is less extensive, 
little disturbance arises, as the oil is soon broken up into droplets and passes through 
the pulmonary capillaries; small parts of it may disappear into tissue spaces while 
globules caught in any tiny vessel are shortly surrounded by leucocytes and also acted 
upon in all probability by blood lipase. After fractures the blood may contain a 
really great excess of fat, usually, to be sure, in fine emulsion. There are at present no 
definite facts covering the relationship between the amount of fat in the blood and 
the occurrence of symptoms of fat embolism. (See Fig. 4.) 

Seats of Embolism.- — -The final place of lodgment of an embolus 
depends mainly on its source. Those derived from the general venous 
circulation are usually carried through the right heart to the lungs, where 
they occlude branches of the pulmonary artery; such accidents not in- 
frequently occur after surgical operations on the lower abdomen, pelvis 
and thighs. Emboli in the portal circulation may lodge in the liver, or 
pass through the liver to the heart and lungs. 

Retrograde Embolism. — Sometimes portions of thrombi, tumor 
masses, other cellular emboli, or micro-organisms may be transported 
in the veins in a direction opposite to the normal blood-current. Thus 
emboli may be carried upward in the inferior vena cava and into the 
hepatic veins and so into the liver; or from any of the larger veins or 
even from the right heart backward toward the peripheral veins. This 



70 



A TEXT-BOOK OF PATHOLOGY 



condition, known as retrograde embolism, is observed when some pul- 
monary disease, such as whooping-cough, emphysema, etc., causes in- 
creased intrathoracic pressure and consequently a positive instead of 
negative pressure in the large intrathoracic veins. There may be an 
actual retrograde current of blood, or the centrifugal transportation of 
the embolus may be more gradually accomplished by repeated impulses 
directed toward the periphery, each of which pushes it a little further. 

Emboli coming from the left heart or from the aorta are distributed 
in the general arterial circulation. They are most frequently found 
in the spleen, kidneys, and brain. Other organs or the peripheral vessels 
may likewise be affected, but the results of embolism are less marked 
in them and are frequently overlooked. Emboli from the veins may 
reach the general circulation in cases in which the foramen ovale or 
septum ventriculorum is perforated (paradoxical embolism), or by being 
broken up into smaller emboli in the lungs and thus passing through the 
pulmonary capillaries. The latter is not infrequent in cases of fat- 
embolism of the lungs. 

Results of Embolism. — A large embolus may cause sudden death 
by occluding one of the main branches of the pulmonary artery, one of 
the coronary arteries, or a large cerebral vessel. If the vessel is 
wholly occluded, secondary thrombosis may complete the obstruction 
and death may be slow. In the case of less important vessels merely local 
anemia results. This may be relieved by establishment of collateral 
circulation, or may cause more or less extensive necrosis if not relieved. 
The original embolus and the secondary thrombus may undergo soften- 
ing or organization in the same manner as ordinary thrombi (q. v.). 

The results of occlusion of smaller vessels by emboli depend on the 
nature of the embolus. They are either purely mechanical when the 
embolus is aseptic, or septic when the embolus contains micro-organisms. 
The important mechanical result of small emboli is the pathological con- 
dition called infarction. 

Metastasis. — The process of metastasis of tumors and of infectious 
diseases is closely allied to that of ordinary embolism, and should be 
considered as that form of embolism in which there arises at the point 
of settlement a condition similar to that at its origin. Small particles 
of tumors in the one case, or of infected thrombi or tissue in the other, 
enter the blood-vessels or the lymphatic channels and are carried to 
neighboring or distant parts of the body, where they lodge in capillary 
vessels. In the case of tumor-embolism the embolus itself grows into 
a new tumor nodule, the local tissue forming the stroma; in case of infec- 
tious processes secondary foci of the infectious disease result, the local 
tissue supplying the inflammatory exudate. 

INFARCTION 

Infarcts occur in situations in which there are small arteries having 
only capillary or, at most, very slight arterial anastomosis with neigh- 
boring arteries. Such arteries were called end-arteries by Cohnheim. 
They are found especially in the kidney, spleen, lungs, retina,base of the 
brain, and parts of the heart. When one of these is occluded by an em- 
bolus infarction may occur. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 71 

Infarcts are situated in the peripheral part of the organ, and are harder 
than the surrounding tissue. They are wedge shaped, the base being 
outward toward the periphery of the organ. Infarcts may sometimes 
result from occlusion of a number of adjoining arterioles or capillaries, and 
in this case are irregular in outline. There are two forms of infarction, 
the red or hemorrhagic, and the white or anemic. The former are dark 
red in color, and have the appearance of wedgeshaped areas of hemorrhage 
with coagulation. Anemic or white infarct's present the same general 
features, but are less elevated and are yellowish or grayish in color. They 
are frequently surrounded by a zone 
of congestion or hemorrhage (Fig. 5) . 

Formation of Infarcts. — The 
first effect of occlusion of an end- 
artery by an embolus is stoppage 
of the circulation beyond the em- 
bolus. A wedge-shaped anemic area 
results. This may remain anemic 
and undergo coagulation necrosis, 
with the formation of an anemic 
or white infarct. In other cases, 
however, the vessels of the oc- 
cluded area, after a temporary 
period of anemia, become overfilled 
with blood, extravasation occurs, 
and a hemorrhagic infarct results. 
Various theories are offered to ex- 
plain the persistence of anemia in 
the first case and the overfilling 
with blood in the second. In 
anemic infarcts the persistent 
anemia in some cases is due to 
thrombosis in the venules which 
receive the blood from the occluded 

end-artery and in the anastomotic Fig. 5.— Old anemic infarct of spleen. 

capillaries. At times rapid swell- 
ing of the parenchymatous cells of the organ compresses the capil- 
laries and maintains the anemia. When muscular contraction or 
collateral compression takes place it is relatively easy to understand 
how the blood from adjoining parts would fail to slip into the anemic 
areas. Some contend that white infarcts are frequently formed by rapid 
absorption and removal of the coloring-matter of the blood from hemor- 
rhagic infarcts. In the latter the overfilling of the vessels results either 
from a back flow of blood from the veins (Cohnheim) or from free capillary 
anastomosis. The latter would be especially apt to occur when the 
general or local blood-pressure was previously elevated, or when the lodg- 
ment of the embolus caused reflex contraction of the surrounding vessels, 
and thus overflow of blood into the occluded area through the capillary 
anastomoses. The hyperemia thus produced soon leads to extravasation 
of blood, because the vessels of the occluded areas rapidly undergo de- 
generative changes. The continuance of the dark color in the hemor- 




72 



A TEXT-BOOK OF PATHOLOGY 



rhagic infarct is due to deposition of iron-bearing pigment derived from 
hemolysis by autolytic or tissue enzymes. Infarcts in the lungs are 
nearly always hemorrhagic; those in the kidneys and especially the 
spleen are frequently anemic. In the brain irregularly shaped areas 
of anemic necrosis (softening) are the usual result. 




Anemic 
Infarct 





Anemi c 
In/arc T 
wi'tk 
Coagulation 
Necrosis 



Fig. 6. — Semidiagrammatie presentation of the production of an infarct, without anasto- 
mosis, with anastomosis, and with lateral compression by hemorrhage. 



Subsequent Changes. — In anemic infarcts cellular necrosis pro- 
ceeds fairly rapidly; due in all probability to autolytic changes by intra- 
cellular enzymes; the coagulum that forms early may remain to be 
later replaced by fibrous tissue, or undergo necrosis. The broken-down 
tissue is gradually absorbed and reactive inflammation and organization 
cause cicatrization. Not infrequently a small amount of calcareous mat- 
ter is deposited, especially in infarcts of the lungs. In hemorrhagic 
infarcts the extravasated blood breaks up into pigment matter and the 
tissues suffer degenerations similar to those seen in anemic infarcts. 
The final result in either case is generally a scar, which is pigmented in 
cases of hemorrhagic infarcts, and it is probable that regeneration of the 
parenchyma rarely takes place; this seems surely to be the case in the 
myocardium. Occasionally infarcts undergo liquefaction and cyst 
formation, especially in the brain. The infarct may become infected 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 73 

by micro-organisms after its formation and abscess may result, as in 
cases in which the embolus itself was an infectious one. 

Infectious embolism occurs in cases of purulent softening of 
thrombi, in cases of local suppuration or necrosis, in ulcerative endocardi- 
tis, and the like. The first effect may be the formation of a hemorrhagic 
or anemic infarct; but the micro-organisms soon multiply and invade the 
tissues, causing suppurative or gangrenous processes. Metastatic ab- 
scesses are produced in this manner. Similar results follow when an 
infarct is secondarily infected. This is not infrequent in the lungs, where 
the air-passages furnish a ready path for the entrance of micro-organisms. 

Pulmonary infarcts may be due to embolic occlusion of the blood-vessels, but 
also to obstruction of a bronchiole. Any kind of hemorrhagic extravasation in the 
lungs may assume a wedge shape, because the area infiltrated is the wedge-shaped 
area included in the divisions of a terminal bronchiole. (For details, see the chapter 
on the Lungs.) 

THROMBOSIS 

. Thrombosis is the coagulation of blood within the blood-vessels or 
heart during life. At the very beginning of the process the formation 
is not a coagulum in the ordinal sense, but subsequently coagulation 
is the ensential feature. After death clots form within the heart and 
vessels, as in blood removed from the body. 

Causes. — The conditions favorable to thrombosis are alterations 
in the blood-current, changes in the vessel walls, and alterations in the 
blood tself. For the most part two or all of these conditions are present 
in cases of thrombosis. 

Alterations in the Blood-current. — Anything which slows the current, 
such as narrowing of the blood-vessels, weakness of the heart, or pressure 
upon the vessels, favors thrombosis. Complete arrest of the current in a 
part may lead to ordinary clotting, such as occurs postmortem; but with 
careful precautions a vessel may be ligated at two points without the 
occurrence of clotting in the occluded portion — at least for a long time. 
Some change in the blood-vessel wall is generally necessary in addition. 
Some sudden change in blood-pressure or rate of flow, some back pres- 
sure or blood eddy may permit the settling upon the intima of sufficient 
blood-platelets to start a clot. Thrombi due to slowing of the current are 
frequently seen in the heart, the vessels of the lower extremities, and in 
the sinuses of the brain in the course of exhausting fevers or other asthenic 
conditions. They are called marantic thrombi. In many of the latter 
micro-organisms have important etiological relations. 

Changes in the vessel walls play an important part. Atheroma, 
inflammatory or degenerative changes in the vessels of areas of inflam- 
mation or necrosis, ligation and other traumatic injuries, and diseases of 
the endocardium are all examples of conditions leading to thrombosis. 
In many cases of thrombosis apparently due to slowing of the current 
of blood micro-organisms have been the more important factors by caus- 
ing primary infective lesions of the endothelium. Dilatation of the arteries 
(aneurysm) or veins (phlebectasia) or of the cavities of the heart acts largely 
by slowing the current of blood or by producing irregular currents. 



74 



A TEXT-BOOK OF PATHOLOGY 



Alterations in the Blood. — It is believed by Aschoff that some altera- 
tion in the blood itself is necessary, and that without this, changes in the 
vessel wall are insufficient. These blood alterations may consist of 
clumping of platelets, collections of hemolyzed red blood-cells, and the 
like. 

Experimentally, thrombosis may be induced by injection into the 
circulation of extracts of the thymus gland, the suprarenal bodies, the 
testicles, and other organs. These extracts contain large quantities of 
the fibrin-ferment regarded by Schmidt as an essential factor in coagula- 
tion. Pathologically, it is probable that the tendency to thrombosis in 
typhoid fever, sepsis, and other diseases is due to increase of similar 
fibrin-forming factors in the blood. The name ferment thrombosis is 
applied in these cases. 

The presence of bacteria in the blood in cases of thrombosis and 
within the thrombi themselves indicates a probable relationship of great 
importance. Some bacteria (especially staphylococci) seem particularly 
potent, while others apparently have little effect. The mode of action 
of the bacteria has not been fully established, but hemolytic activity and 
injurious effects on the fining of the blood-vessels may now be considered 
sufficient to explain thrombosis, on the basis of a reduction of the anti- 
coagulating power of endothelium. Bacteria seem able to induce hyper- 
inosis, or an increase in the fibrin-forming elements. 

Hemolytic action is also the probable explanation of the frequent 
thrombosis met with in various mineral poisonings and in auto -intoxica- 
tion such as follows freezing or burns. 

According to present-day views, coagulation of the blood is the result of a special 
form of gelatinous precipitation of fibrinogen, a normal constituent of the blood- 
plasma under the influence of fibrin-ferment or thrombin. The latter is probably 
not a true ferment in its mode of action, but seems rather to enter into a physical 
or physicochemical combintaion with the fibrinogen. Thrombin is a derivative 
of various cells of the body, especially the leukocytes and vascular endothelia. It 
occurs in the cells as -prothrombin, which requires for its activation or conversion into 
thrombin, calcium salts and probably also certain so-called thromboplastic substances 
derived from tissues. In the blood within normal blood-vessels coagulation is pre- 
vented by the action of antithrombin (Howell). According to the views here ex- 
pressed the process of coagulation may be tabulated as follows: 

Cells— ^thromboplastic substance. Thromboplastic substance + calcium + pro- 
thrombin = thrombin. Thrombin + fibrinogen = fibrin. 

Pathological Anatomy. — The appearance and the construction of 
thrombi depend upon the manner of formation. 

When formed in consequence of almost complete stoppage of the 
circulation they are dark-colored, soft, red clots, similar in every way 
to postmortem coagula, and under the microscope show fibrillar fibrin 
enclosing mainly red corpuscles. 

Yellowish or white thrombi are formed slowly from actively cir- 
culating blood and are more consistent. Their composition will be under- 
stood from the mode of formation. In the normal circulation the red 
corpuscles move in a column in the center of the stream, separated from 
the wall of the vessel by a plasmatic zone in which the leukocytes may be 
seen. When the circulation is slowed, plaques approach the vessel wall, 
and tend to adhere in small masses to any point of disease in the endo- 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



75 



t helium and also to each other. This has been termed conglutination 
of the blood-plaques. 

In the ordinary thrombus, after primary conglutination of the plaques, 
leukocytes are added, and red corpuscles in great or small numbers, 
according to the manner of formation of the clot, whether rapid or slow. 

White thrombi consist of conglutinated 
plaques, leukocytes, and fibrin. They 
first appear as hyaline, viscid masses, 
but subsequently become granular 
from partial disintegration. If the 
circulation is alternately slow and 
more rapid, distinct layers are seen in 
the thrombus, first dark colored 
from admixture of red corpuscles, 
then fighter in hue. Such thrombi 
are called stratified. If the circulation 





Fig. 7. — Complete thrombosis of in- 
ferior cava and iliac veins, from an infective 
endophlebitis shown by the roughening 
and opacity on the intima where the 
right vein is laid open. 



Fig. 8. — Cystic thrombi of heart chamber. 



is irregular from dilatation of the vessels or from other causes, the fight 
and dark areas of the thrombus may be more irregularly disposed. 

The thrombus first formed is the primary thrombus. Subsequently 
it extends by additions {secondary thrombus) in the direction of the 
current of blood as far as the next collateral branch of the vein or artery, 
into which the thrombus frequently extends as a rounded prominence. 
In the case of the veins a new thrombus may start from such projection 
(Fig. 7), and eventually the clot may in rare cases extend as far as the 



76 



A TEXT-BOOK OF PATHOLOGY 



heart. The thrombus may be lateral — that is, when it lies against the 
vessel wall — or obstructive, when the lumen is completely obliterated. 
In the veins small thrombi are frequently formed in the valvular 
pouches in marantic subjects. In the heart thrombi are especially com- 
mon on diseased valves, in the auricular appendages, and in the inter- 
trabecular spaces (Fig. 8). They frequently appear as po^poid masses, 
and may be attached by slender pedicles. A curious form, called ball 
thrombi, is seen in the auricles. These are rounded clots wholly or almost 
wholly separated from the wall, and m&y occasion serious obstruction 
at the orifices of the heart. The internal softening is probably due to 
leukocytic enzymes acting in the center, protected there from the anti- 
enzyme of the blood. 



Effects. — Frequently the collateral circulation is so quickly estab- 
lished that no untoward results are seen. When a large vein is ob- 
structed, venous congestion and dropsy may follow; obstruction of an 
artery causes local anemia, and subsequently, if the collateral circulation 
is not established, degenerations or necrosis. Thrombotic obstruction 
of small arteries ma} r cause hemorrhagic infarction. Embolism 
if the thrombus is infected, general pyemia may result from softening of 
the thrombus. 

Subsequent Changes.- — After their formation all thrombi contract. 
In this way the red forms may become light colored by extrusion of the 
red corpuscles, or by hemolysis if bacteria or toxins are responsible for the 
thrombosis. In small vessels red thrombi often become light colored 
by removal of hemoglobin and a species of hyalin transformation. These 
may have the appearance of white thrombi and are only distinguished 
by careful examination. 

After the thrombus has contracted it may undergo various de- 
generative changes. Frequently the white corpuscles, plaques, and 
fibrin are broken down by leukocyte enzymes, and the red corpuscles 
converted into granular pigmented masses. These softened portions are 




Fig. 9. — Thrombosis in cardiac 
chambers, showing cyst-like structure 
(Orth). 



Fig. 10. — Branch of the brachial artery . 
after amputation, showing vascularization 
of the thrombus, Th (Weber). 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



77 



swept into the circulation and occasion embolism. Frequently this form 
of simple softening occurs in the center of large thrombi and gives rise to 
cyst-like formations (Fig. 9) ; the center softens because here enzymes can 
act, protected from the antienzyme in the circulating blood that bathes 
the outside of the thrombus. 

A more serious form of softening occurs when the thrombus is in- 
fected by micro-organisms. In this case true purulent softening takes 
place, and the wall of the blood-vessel shares largely in the suppurative 
processes. This form occurs especially in the thrombi blocking blood- 
vessels of suppurating or necrotic tissues. General pyemia and infec- 
tious embolism result. 




Fig. 11. — Organization of a thrombus showing the growth of fibrous tissue into clot 
from the subintimal layers, and the greatly increased blood-vessels of this area. 

A more favorable termination of a thrombus is calcification. This 
is most frequent in the clots in dilated veins, the calcareous thrombi 
being known as phleboliths. Arterioliths and cardioliths are rarely met 
with. 

Organization of the thrombus may result from the irritation it occa- 
sions. New blood-vessels and proliferating connective-tissue cells 
spring from the vasa vasorum and lining membrane of the blood-vessel 
as well as from endothelial cells covering the thrombus, and penetrate 
the thrombus (Fig. 11). From these organization proceeds as elsewhere, 
and as it advances the thrombus itself is absorbed. Finally, the clot is 



78 



A TEXT-BOOK OF PATHOLOGY 



fully replaced by connective tissue enclosing a small amount of blood- 
pigment or calcified remains of the thrombus. The blood-vessel may 
be converted into a solid fibrous cord, or may be distorted and narrowed 
by bands of connective tissue in the interior. Sometimes after partial 
vascularization of a thrombus small vessels running parallel with the 
lumen of the obstructed vessel become dilated and thus partly reestablish 
the channel. This is termed canalization of the thrombus (Fig. 12) 
In other cases canalization may begin as a process of simple softening. 




9 



Fig. 12. — Organized and canalized thrombus, (a) Elastica stained for elastic tissue; 
(b) small vessels penetrating from media; (c) newly formed connective tissue; (d) rem- 
nants of fibrin; (e) remnants of red thrombus masses; (/) blood pigment; (g) dilated 
newly formed vessel (canalization). (Dietrich in Aschoff's Pathologische Anatomic) 

The clotting of blood within body cavities, in extravasations, or upon 
wounds is favored by the presence of tissue coagulins and bacteria in 
addition to the leukocytes and platelets. Hyaline thrombi seen in 
small vessels and free in organs are due to an agglutination of erythro- 
cytes or platelets by bacterial or other toxins. They are probably free 
of fibrin, although staining like it. 

EDEMA 

Definition. — The term " edema" is applied to a condition in which 
the liquid within the tissues is increased in quantity. 

Etiology. — It is primarily necessary to understand the methods by 
which the liquids normally present in the tissues escape from the blood- 
vessels, their original source. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 



79 



Several processes are concerned in this escape of fluid. In the first 
place, the pressure of the blood serves to cause a certain amount of direct 
filtration, just as liquid enclosed in tubes of permeable animal membrane 
escapes when the pressure outside is less than within. In this process of 
direct filtration the state of the tissues themselves plays a part. If the 
normal elasticity of the tissues and degree of pressure of the liquid in the 
interstitial spaces are lowered, liquid escapes through the capillary walls 
to equalize the pressure. A second process at work is that known as 
diffusion or osmosis. In this there is an exchange between the blood and 
the tissue liquids, certain substances being taken into the blood in ex- 
change for water and other constituents of the blood-plasma. The liquid 
thus discharged from the blood-vessels enters into the metabolic activity 
of the tissues to a greater or less degree, is somewhat altered in character, 
and the surplus is carried off in the lymphatic capillaries as lymph. Cer- 
tain physiologists (Heidenhain et al.) believe that there is a further and 
very important factor of a vital sort. This is described as an active 
secretory function of the endothelial cells of the capillaries and lymphatic 
spaces; so that, according to this view, lymph formation is in a measure 
at least a direct secretion. This view, though not generally accepted, is 
supported by many facts. Meltzer suggests that endothelium acts as a 
carrier of lymph and solid particles from the blood to the tissues. 

Briefly, then, lymph formation may be described as the escape of 
water and other substances through a more or less permeable membrane, 
the capillary walls, in consequence of direct filtration, osmosis, and prob- 
ably secretion. The quantity present in the tissues depends upon the 
quantity escaping from the blood-vessels and the amount carried away 
by the lymphatic circulation. 

The causes of increased accumulation of liquid in the tissues may 
then be readily determined. Among these are: (a) increase of blood- 
pressure, or (6) decrease of tissue elasticity and pressure; (c) alterations 
of the blood rendering it more diffusible, or (d) of the liquids in the 
tissues increasing the osmotic power of these; (e) increased permeability 
of the walls of the blood-vessels; (/) obstruction to the flow in the lym- 
phatic vessels. These causes will be considered separately with reference 
to certain well-known clinical types of edema. 

(a) Increased blood-pressure always favors increased escape of 
liquid from the vessels (transudation) and thus increased formation 
of lymph. In active hyperemia with excess of pressure the amount of 
liquid rarely becomes so great that the lymphatic vessels cannot carry it 
off, and edema does not, therefore, occur. In passive congestions, how- 
ever, as in heart disease, pressure upon veins, etc., the escape of liquid 
becomes more rapid and copious, and the lymphatic circulation is insuf- 
ficient. Edema or dropsy results. In this process of direct filtration the 
transudate consists mainly of the water and saline constituents of the 
plasma and to a relatively small degree of the albuminous constituents. 

(6) Decreased tissue elasticity and pressure are rarely factors of 
prime importance, though they may be contributing causes in many 
cases. In one class of cases termed "oedema ex vacuo" they are the 
principal causes. In these cases liquid escapes from the blood-vessels 
to fill a space left vacant by disease or atrophy of tissue elements. This 



80 



A TEXT-BOOK OF PATHOLOGY 



is frequently seen in the subarachnoid spaces of the brain and in other 
parts of the central nervous system. 

(c) Alterations of the blood, though theoretically very important as 
direct causes, probably act indirectly. It has been found by experi- 
ment that artificial hydremia, even though combined with considerable 
increase of the bulk of blood, does not cause edema unless by some 
means the walls of the blood-vessels have been injured. It is probable, 
therefore, that the edema of anemic and marantic persons is similarly 
due to increased permeability of the vessels. This in itself might occa- 
sion edema, though the degree is probably greater as a consequence of 
the anemic state of the blood. The vascular disease itself is probably 
in some way (perhaps by the action of circulating toxic substances) 
brought about by the condition of the blood. 

(d) Increased permeability of the capillary walls is of great im- 
portance and probably plays a part in every case of edema. Experi- 
mentally it is easy to prove that this factor alone may cause pathological 
transudation. Applications of heat to a part or the introduction of 
poisons capable of causing disease of the walls of the blood-vessels may 
thus occasion edema. Clinically this factor is of importance in the 
edema of Bright's disease. Formerly the dropsies of renal disease 
were attributed to hydremia, but the experiments cited above show this 
factor to be insufficient. On the other hand, changes of the vascular system 
are known to occur in Bright's disease, and particularly in cases usually 
attended with marked edema (diffuse nephritis). Changes in the blood 
may, of course, contribute, as may also stasis due to cardiac weakness. 

Disease of the capillary walls is also an important cause of edema 
in and about areas of inflammation (inflammatory edema). In these 
cases the toxic causes and products of inflammation doubtless attack 
the walls of the vessels and render them more porous. Such edema may 
occur only in the vicinity of an inflamed area, or may be widespread. 
Thus in some cases edema of the lungs and other internal organs may be 
occasioned by bacterial toxins derived from a distant focus of infection. 

Cases of hereditary edema have been described. These may owe 
their origin to a congenital excess of vascular permeability. 

Finally, there are cases of edema in which the nervous system seems 
to exercise an influence. Among these are the dropsies attending cases 
of neuritis, neuralgia, or organic diseases of the cord. In these instances 
changes in the blood-vessels and perhaps in the tissue elasticity may be 
important causes. An interesting form of this sort is that known as 
angioneurotic edema, in which local edema of various forms (often as 
giant urticaria) makes its appearance under the influence of nervous 
irritations. 

(e) Obstruction of the lymphatic circulation does not ordinarily 
occasion edema because the collateral circulation is sufficient to carry 
away the lymph. When, however, a larger trunk, especially the thoracic 
duct, or numerous smaller lymphatics are obstructed edema may result. 
This is observed in the chylous ascites due to obstructions of the thoracic 
duct and in the edema of elephantiasis. 

(/) Alterations of the liquids of the tissues may, conceivably, occa- 
sion increased diffusion of liquid, but practically little is known of the 
operation of this element. 



DISTURBANCES OF THE CIRCULATION OF THE BLOOD 81 

While the escape of fluid from vessels to tissues may be explained 
under the preceding headings, other factors must account for its remaining 
outside lymph- and blood-vessels. In the case of the obstructive edemas, 
this is not so difficult to understand, but the nephritic and cardiac dropsies 
offer a problem that has as yet not been properly settled. The theory of 
Fischer that tissue colloids, under the influence of increased acids due to 
imperfect metabolism, swell up and hold considerable water, has not 
received general acceptance. In nephritis there is salt retention and this 
is in a measure true in the stasis of cardiac decompensation. Edema 
seems roughly proportional to salt retention and withdrawal of this 
chemical from the diet is followed by a reduction of edema. However, 
there are some cases in which salt retention has not been accompanied by 
dropsy and dropsy without marked reduction in salt excretion has been 
seen. It would seem that other factors, such as changes in blood 
pressure and the capillary walls, must be considered, and indeed it is 
doubtful whether one cause is at the basis of all edemas. Increased 
fluid blood (plethora or hydremia), with or without increased blood 
pressure, could be potent in the presence of local factors (stasis in the 
lower extremities) . 

Pathological Anatomy. — Edema may take various forms, according 
to its situation. In some cases it is localized, affecting a limited part of 
the body, as a single organ or member. In other cases it is widespread 
in the subcutaneous tissues and skin, when the term "anasarca" is ap- 
plied. It may occur in the serous cavities in the form of serous transu- 
dates (hydrothorax, ascites, hydropericardium, etc.). 

The liquid itself varies in character according to the cause. In the 
pure transudates due to increased filtration the liquid is watery, low 
in specific gravity (below 1016), and comparatively poor in blood- 
corpuscles and albuminous constituents. In cases in which disease of 
the vessel walls has played a large part in the causation, especially in 
the inflammatory edemas, the liquid is more dense and contains more 
corpuscles and albuminous bodies. 

The transudate first occupies the lymph-spaces or interstices of the 
tissues, causing a more or less uniform swelling and bogginess. The 
tissue pits on pressure, and on section more or less abundant liquid 
exudes. The solid organs (kidneys, liver) are lighter in color, less dense, 
and more moist on section than normal; but the appearances of edema 
are here less characteristic than in the subcutaneous or submucous 
tissues, or in the softer organs like the lungs and brain. 

Microscopically, the tissue elements are seen to be pushed apart 
by the transudate, and in some cases the cells themselves may be dis- 
eased. (See Dropsical Infiltration.) 

Results of Edema. — The function of edematous parts is necessarily 
impaired. Sometimes serious consequences ensue, as in the case of 
edema of the epiglottis, the lungs, or the brain. Secondary changes 
may occur in parts the seat of continued edema. Among these are 
various degenerations of the cells and a productive change in the con- 
nective tissues. The latter is well illustrated in the sclerotic change in 
the subcutaneous tissues of long-standing dropsy, elephantiasis, etc. 



6 



CHAPTER IV 



RETROGRESSIVE PROCESSES 
ATROPHY 

Definition. — Atrophy is a condition in which a tissue or organ under- 
goes a more or less uniform diminution without definite disease of its 
constituent parts. It is extremely difficult to draw a sharp fine between 
atrophy and degeneration. Frequently one of these conditions merges 
into the other. 

Hypoplasia. — This term is applied to a condition in which certain organs or 
tissues fail of their normal development. Thus the heart and blood-vessels and the 
internal genitalia have been found incompletely developed in some cases of chlorosis; 
and similar conditions have been found in other diseases or apart from manifest 
disease. It is difficult to determine in some cases whether the lack of development is 
purely the result of deficiency in the developmental prooesses or the result of congen- 
ital disease. Thus, in the state called infantilism, in which the body as a whole 
remains undeveloped, there is sometimes a relationship with cretinism or other dis- 
eases of glands of internal secretion, and primary disordered action or deficiency of 
the thyroid gland, hypophysis, etc., is the underlying cause. Occasionally an organ 
or part of the body is entirely wanting. To this condition the name aplasia is given. 

Etiology. — The causes of atrophy may be varied. It occurs as a 
result of want of functional demand, as in the atrophies affecting palsied 
limbs or those immobilized for a fracture; and sometimes as a result 
of disturbances of the tropic nervous system, as in diseases of the anterior 
horns of the spinal gray matter. In the latter instances lack of use is a 
contributing cause. One of the commonest forms of atrophy and 
one that might be considered as physiological, is that seen in senility and 
evidenced by arcus senilis, decreased size of the heart, glossy skin, 
rarefied and fragile bones and the disappearance of muscular and elastic 
tissues in the arteries. Similar normal or physiological atrophy occurs 
in certain organs before the general manifestations of old age. Thus, 
the atrophy of the thymus gland in early childhood and of the genital 
organs at the menopause are instances of cessation of function, and conse- 
quent or concomitant atrophy of physiological character. Atrophy may 
be more definitely pathological and the result of distinct causes, such as 
want of local or general nourishment by occlusion of the vessels, pressure, 
etc. In these cases the process may be purely atrophic, or there may be 
distinct degenerative disease of the cells with diminution of bulk. 

Pathological Anatomy. — Atrophy may be simple or numerical. In 
the former kind, to which the term "true atrophy' 7 might also be applied, 
the individual cells decrease in size without manifest disease; in the latter 
the cells are reduced in number, and are usually first altered by some 
form of degenerative disease, so that the process is not, strictly speaking, 

82 



RETROGRESSIVE PROCESSES 



83 



true atrophy. The parenchyma of organs suffers first and most char- 
acteristically, the connective tissues remaining unaffected or even 
undergoing hyperplasia. . In true atrophy the cells may present no 



r»d. I 




Normal 



(entire absence ) 



Aplasia 



f,' 9 .3. 
l8|fl|llfl]P| 



Hypopi* 



Atrophy 




Hypertrophy 




fu,. f 




Hyperplasia Metaplasia 

Fig. 13. — Retrogressive and progressive changes contrasted. 

definite alteration, excepting perhaps slightly increased pigmentation. 
This is sometimes due to the fact that the normal pigment does 
not suffer reduction as do the other constituents of the cell, but in 
other cases there is actual deposition of pigment, of the group of poorly 
understood lipochromes. Cases of the latter 
kind are designated as brown atrophy (Fig. 14). w —: :r] ^ 
This is seen most strikingly in the heart muscle 
in advanced old age or in persons dead of some 
chronic cachectic disease. In some of the con- 
ditions generally described as atrophy the cells 
show degenerations of various forms, such as 
cloudy swelling, coagulation necrosis, fatty de- 
generation with vacuolization, and other gross 
alterations of structure. 

The physicochemical processes at work in 
atrophy while not thoroughly understood are 
probably not the same for all cases. In physio- 
logical atrophies, such as the involution of the uterus, autolysis seems to 
lie at the bottom of the matter and this might also explain those forms 
due to reduction of blood supply with the resulting partial asphyxia 
and absence of the antiferment of the blood. For the neuropathic forms 



i r 

if i 

■■: I 



Fig. 14. — Brown atrophy 
of the heart muscle. 



84 



A TEXT-BOOK OF PATHOLOGY 



the operation of the just mentioned factors is not -so clearly compre- 
hensible. 

Secondary degenerative changes may occur in the connective tissues 
after the parenchyma cells have become atrophic. Thus, after the physio- 
logical atrophy of the thymus gland has occurred the connective tissues 
of the gland and of the surrounding parts become converted into fatty 
tissue. In other cases myxomatous change may be observed. Such 
a fatty or myxomatous change may give rise to pseudohypertrophy. 

Organs which have undergone atrophy are often quite irregular on 
the surface from unequal involvement of the different constituents. 
The consistency may be little changed or may be greatly reduced, par- 
ticularly when some form of cellular degeneration is present. On the 
other hand, the organ may be hard and tough from secondary hyper- 
plasia of the connective tissue. The capsule is generally wrinkled from 
the shrinkage of its contents, and secondary thickening is not unusual, 
especially in the heart and spleen. The color of the organ, like that of 
the individual cells, often becomes darker than normal, and may be 
decidedly changed in brown atrophy. 

In cases of pressure-atrophy various distortions of the affected 
organ may be observed. These are particularly marked in the livers of 
women who have laced excessively. The right lobe of the organ often 
presents a deep groove or furrow corresponding with the lower border 
of the ribs, and each of the ribs with which the organ comes in contact 
may cause a depression. The caries that occurs in bones adjacent to a 
tumor or aneurysm, or the disappearance of parenchymal cells around a 
visceral cyst, are also examples of pressure atrophy. 

Pathological Physiology. — The function of an atrophic organ is 
necessarily impaired. In the atrophies of old age this may be of little 
consequence, as the functional demand grows less and less. In premature 
atrophies general as well as local disturbances may occur. These dis- 
turbances vary with the varying functions of the organs, and will be 
separately discussed. 

THE SO-CALLED INFILTRATIONS AND DEGENERATIONS 

There are certain pathological processes of a retrogressive character 
to which the names "infiltration" and "degeneration" have been given. 
Data are growing to show that several of these may be but stages of cell 
necrosis, and that a sharp distinction is not possible between infiltration 
and degeneration. In order not to confuse the reader the subjects 
will be taken up under their customary names and an attempt will be 
made to show their relationships. 

CLOUDY SWELLING 

Definition. — Cloudy swelling, also termed "albuminous infiltra- 
tion" and "parenchymatous degeneration," may be defined as an 
edema of the cellular protoplasm, with granular alteration in the pro- 
toplasmic protein and the production of opacity. 

Etiology. — Cloudy swelling is an almost universal accompaniment 
of inflammations. Circulatory disturbances (anemia) were formerly 
supposed to be important, but are now considered to be of little sig- 



RETROGRESSIVE PROCESSES 



85 



nificance. Fever per se can produce cloudy swelling, probably not so 
much the result of the simple degree of heat as of metabolic disturbances 
induced thereby. The most frequent cause of cloudy swelling is in- 
toxication, either by bacterial toxins, as in the various infectious con- 
ditions, or by innumerable organic and inorganic substances. Cloudy 
swelling is also caused by nutritional disturbances; starvation of an 
organ will produce it, as the first stage of atrophy and conversely exces- 
sive nutritional states or great secretory activitj' may cause a cell 
to assume an appearance simulating this condition, as in the glandular 
epithelium of the liver during active digestion. Nerve stimulation of 
glands particularly related to the nervous mechanism may give rise to 
similar changes. These latter processes should be viewed as normal phe- 
nomena analogous to the physiological degenerations. . 




"mm- 

Fig. 15. — Cloudy swelling and necrosis of the epithelial cells of the renal tubules, due to 
sublimate-poisoning (Karg and Schmorl). 




Pathological Anatomy. — The swollen cells present a fine opacity 
which under high powers is seen to be due to the presence of diffuse refrac- 
tile granules (Fig. 15) . The normal protoplasmic granulations (Altmann's 
granules) may partly or wholly disappear; in muscle-fibers the stria- 
tions are obscured or obliterated. Vacuolation may be seen in the late 
stages. The cell wall becomes indistinct, so that the cells appear to have 
coalesced. The nuclei may be little altered, but are commonly obscured 
by the degeneration. The nuclei are somewhat more deeply stained 
at first, but shortly undergo some chromatolysis, becoming indistinct 
when their sharpness is destroyed by both the smaller cytoplasm and 
their own degeneration. Generally the chromatin becomes diffusely 
stained; it may elect the acid stains or may refuse all staining. In 
late stages the entire cell may lose its normal reactions to staining 
reagents. The distinctive granules are not soluble in alcohol or ether, 
but are dissolved by acetic acid and alkalies. Cloudy swelling may 
be the forerunner of, or at least go over into, fatty degeneration. 

The large glandular organs, the liver and kidneys, illustrate the 
condition exquisitely. The entire organ is symmetrical^ swollen; the 



86 



A TEXT-BOOK OF PATHOLOGY 



general consistency perhaps a little decreased. On section, the surface 
may be found a little moist and the parenchyma protrudes. The tissue 
presents an opaque pallor, suggesting the appearance of boiled flesh. 

Seats. — The glandular epithelia (liver and kidney) and the muscle- 
fibers are the striking seats of this degeneration. 

Pathological Physiology. — -The opacity seems to be due to a coagu- 
lation or precipitation of a part or all of the protoplasmic protein. Some 
systematic writers have attempted to divide it into two groups: albu- 
minous infiltration, in which the material has been deposited in the 
cell and then precipitated; and albuminous degeneration, in which 
the inherent cellular protein has been precipitated. It is doubtful 
whether this division is justified. The chemical relations are entirely 
obscure. It is as yet incomprehensible how bacterial toxins, them- 
selves apparently proteins, can precipitate other and higher proteins. 
In the case of inorganic poisoning (metallic salts, acids) the process 
is more readily understood. The swelling of the cell is possibly a simple 
edema, due to disturbed osmotic relations, by some explained as the 
result cf increase affinity of colloids for water by increase in acids. While 
this may or may not be so, the swollen state of the cell is credibly ex- 
plained as the action of intracellular enzymes, possibly activated by the 
original cause of the condition, with the precipitation of proteins and 
separation of water. 

Bell thinks that fatty and dropsical conditions of the organs give 
the gross appearance of cloudy swelling, and that all such degenerations 
need not be of the same microscopical appearance. He thus believes 
that the gross diagnosis "cloudy swelling" covers several states, and even 
the minute picture does not indicate an entity. One form in which the 
granules are coarse and easily visible has been termed "granular dis- 
integration" and resembles certain low grade dropsical degenerations. 

The function of organs is more or less disturbed by this form of 
degeneration. Complete recovery is easy and frequent. If, however, 
the causes persist, the cells pass into other degenerations, usually fatty 
metamorphosis. 

FATTY INFILTRATION 

Definition. — -Fatty infiltration is the deposition of fats derived 
from the circulation in cells and tissues which normally contain none, 
or the deposition of an excess of fats in cells and tissues in which it nor- 
mally occurs. It is well to restrict this term to those cases where one or 
two large globules of fat exist, with little or no pathological change in the 
cytoplasm, for fatty degeneration is also partly an infiltration process in 
a diseased cell. 

Etiology. — Fatty infiltration may be physiological or pathological. 
In conditions of general obesity the regular consumption of excessive 
quantities of nourishment may lead to the most marked degrees of fatty 
infiltration; an inherited predisposition and lack of exercise act as 
contributing causes. In rare instances it seems possible that with the 
normal physiological diet persons of exceptional digestive power and 
living under conditions which restrict combustion may become affected 
with pathological fatty infiltration. The condition may occur during 



RETROGRESSIVE PROCESSES 



87 



pregnancy, and is frequent at the menopause. In a large class of cases 
an abnormal diet, or the presence in the diet of substances which aid in 
the formation of fats, such as alcohol, are responsible for the condition. 
It is doubtful whether poisons produce general fatty infiltration; they 
frequently, however, indirectly produce local or visceral infiltrations; 
arsenic and antimony are examples. In cachexias certain organs may 
become loaded with fats, as is sometimes seen in the liver in phthisis. In 
carcinoma the cells of the neoplasm may become infiltrated with fats. 
In organic diseases of the nervous system accompanied by extensive dis- 
integration of myelin, in bone diseases, and even following fractures 
of or operations on bones, the liberated fats are taken up by the circula 
tion and deposited in susceptible localities. There is a rare form prob- 
ably entirely of senile origin, and also a type which appears at puberty, 



associated with disease of the pitutiary body. Of general diseases 
that may cause general fatty infiltration, chlorosis and diabetes may be 
mentioned. Fats may be deposited locally as substitution tissue, as 
in the capsule about sclerosed kidneys, in the place of atrophied 
muscular fibers, in the bones, and about areas of local disease. The 
protective areas of fibrous tissue which wall off pathological processes of 
various kinds may become extensively infiltrated. There is some reason 
to believe that fat may be laid down and later reabsorbed or removed 
to another locality. 

Pathological Anatomy. — The fat may be diffuse, in localized areas, 
or in streaks along the planes of fibrous tissue. The appearances naturally 
vary with the tissue affected. The connective tissue rather than the 
parenchyma usually displays the disease. The microscopical picture in 
connective tissues is precisely the same as that of normal adipose tissue. 
The deposits in connective tissue are most prominent in various fascice 
and along the fibrous strands, under the endothelial membranes, about 
the lymph-channels, between the muscular fibrillar, and to a marked 
extent just beneath the true skin. In the kidney the collections are be- 
tween the tubules; in the liver, in the fibrous trabecule, but especially 
in the hepatic cells; in the heart, underneath the. serosa and between the 




Fig. 16. — Fatty infiltration of the liver. 



88 



A TEXT-BOOK OF PATHOLOGY 



bundles of fibers. Within the parenchyma cells, and this is most marked 
in glandular epithelial cells, the fat is seen as distinct drops within the 
cell wall. The fat-drops are always of considerable size, and soon run 
together, forming one drop, which pushes the protoplasm and nucleus 
against the cell wall, giving the so-called seal-ring appearance. The 
nuclei, though flattened, are usually normally distinct, show a nucleolus, 
and stain well; the cell protoplasm is clear and presents its normal 
granules; the cell wall is intact, though often bulging to accommodate 
the excess of contents. In rare, prolonged, and extreme instances the 
bulk of the fat may be such as to interfere with the functions and 
nutrition of the cells, whose nuclei and protoplasm will then show 
pathological alterations. Crystalline formations, as of margarin and 
cholesterin, and tiny balls of lecithin may be present, but are more 
often seen in fatty degenerations. The fat may be stained 
with osmic acid or sudan III. 

Seats. — The favorite seats of fatty infiltration are the subcutaneous 
and subserous tissues, the mesenteries and omentum, along the fasciae, 
between the muscles, about the kidneys, and in the liver and heart. 
The lungs and central nervous organs are rarely and only slightly affected. 

Pathological Physiology. — The above description is intended to 
define this condition rigidly as an infiltration of fat into otherwise normal 
cells or tissues, distinct from any possible formation of fat in them. 
Infiltration arises whenever there is an abnormal quantity of fat in 
the circulation; the causes of this were pointed out in the etiology. 
Infiltration into imperfect or diseased cells may, however, occur with 
only normal quantities of circulating fat. All cells and tissues are not 
of the same degree of susceptibility; when, therefore, isolated areas occur 
in unusual localities a pre-existing disease should be suspected. 

The assumption of fat and its retention in the form of globules must 
be referred to an inadequacy of the oxidative powers of the cell. This 
same is true for fatty degeneration, but here we may have added 
a destruction of the natural fat combination in the cell and both forms tend 
to remain in small globules or granules. 

Unless very extreme, fatty infiltration does not seriously embarrass 
the functions nor threaten the existence of tissues, and complete recov- 
ery and restitution are the rule. It may, however, cause mechanical em- 
barrassment or may lead to secondary degenerations, which, particularly 
in the heart, may be of consequence to the organ. 

FATTY DEGENERATION 

Definition. — This was formerly defined as a metamorphosis, the con- 
version of the cellular protoplasm into fat, but is now looked upon as a 
combination in which this process is of less importance than the deposi- 
tion of fat, fatty acids or lipoids in small particles into a diseased cell 
or that cannot oxidize them. The classical physiological illustration is 
the fat production in the secretion of milk. Here the nature of this 
process has not, however, been determined. The majority of the secreting 
cells neither die nor show pathological alterations; while in the case of 
such as are cast off, as colostrum cells, it has not been shown that their 
fat was not an infiltration. 



RETROGRESSIVE PROCESSES 



89 



Etiology. — Fatty degenerations frequently follow upon cloudy 
swelling, and the causes detailed for the one apply also to the other. 
Of all agents, poisons are the most important. These may be metallic, 
as mercury, arsenic, lead, phosphorus — indeed, most of the metals. 
Compounds which directly bind the hemoglobin or reduce it, or break up 
the red corpuscles, likewise produce it; such are carbonic oxid, chlor- 
ates, pyrogallic acid, some coal-tar compounds, etc. Certain poisons, 
like chloroform, ether, iodoform, and the acids, seem to act directly on 
the cell nutrition. In the case of most of these substances it seems to 
have been shown in more or less accurate chemical studies that the 
poison acts by disturbance of the cellular metabolism. The toxins 
of bacteria are causes of importance, but their mode of action is not 
clear, and the analogy with the metallic posions which naturally sug- 
gests itself has not been made out. In anemias and cachexias fatty 
degeneration is common; it is rare in uncomplicated chlorosis. The 
degeneration in these cases was formerly regarded as due to suboxida- 
tion. Since, however, it has been shown that no suboxidation occurs 
in such chronic anemias, the degeneration may best be classed as toxic. 
It seems possible, however, that extreme hemorrhage can produce 
fatty degeneration by suboxidation. Metabolic diseases can also pro- 
duce it, as is sometimes seen in diabetes. Fever can produce it, but the 
temperature must be high and prolonged. 

Local fatty degenerations may be caused by local disturbances in. 
nutrition, if not too sudden. This is seen in cases of congestion, throm- 
bosis, embolism, atheroma, in tumors, and in tuberculous and syph- 
ilitic deposits. The fatty changes of senility are probably of like origin. 
In the involution of tissues, as in the thymus, corpus luteum, uterus, etc., 
fatty degenerations are common. Trophic disturbances produce the 
degeneration, as is seen in the voluntary muscles. In many pathological 
processes, as in caseation, liquefaction necrosis, and the resolution of 
pneumonia, this metamorphosis plays as important role. In rare 
instances, as mentioned, fatty infiltration may pass into fatty 
degeneration. 

Pathological Anatomy. — Organs the subject of marked fatty de- 
generation are often somewhat increased in size; to this, however, there 
are many exceptions: a notable one is acute yellow atrophy of the liver. 
The consistency is usually lessened, though associated fibrosis may render 
the affected part abnormally dense. The specific gravity of the tissue 
is notably reduced. In the nervous system and in caseation and allied 
conditions liquefaction may occur. The color in typical instances is a 
pale yellow; the existence and degree of congestion, pigmentation, jaun- 
dice, or other associated conditions will obviously alter the color. The 
areas of degeneration may be uniform or isolated. In the heart and liver 
particularly streaks or irregular areas may produce a mottled appearance. 
On section, free fat may drip from the knife and cut surface; in other cases 
no fat-droplets can be seen macroscopically. In rare instances crystals 
may be visible to the naked eye. 

Microscopical Appearances. — The parenchyma cells are first and most 
extensively affected, though the connective tissue may become involved. 
The cells are usually somewhat enlarged. The natural granules of the 



90 



A TEXT-BOOK OF PATHOLOGY 



protoplasm disappear, and in their stead are fine dark granules, which 
usually stain black with osmic acid (Fig. 17), and which are dissolved 
by alcohol, ether, etc., but not by acetic acid. A peculiar reaction of the 
granules is their staining with fuchsin (fuchsinophile granules). Usually 
the granules are very fine and only slightly refractile; they may, however, 
be large, and considerable droplets may appear or the entire cell become 
one large fat-drop, as in fatty infiltration. The nuclei in many cases 
of moderate degree show no changes; later in the process, however, the 
chromatin becomes diffused and refuses to stain and the nucleus may 



•V 



• : n 




Fig. 17. — Fatty degeneration of the epithelium of the renal tubules; stained with osmic 

acid (Simmonds). 

entirely disappear. When the fat is dissolved out of the cell a vacuolated 
protoplasm may be observed. In early stages the protoplasm has been 
asserted to be unaltered when thus examined. The cell membrane sooner 
or later breaks down, and the fatty contents and detritus fill the space. 
Cholesterin, lecithin, and fatty crystalline formations are often seen. 

Seats. — Fatty degeneration occurs in nearly all tissues. The epi- 
thelial structures, especially the liver and kidneys, the heart muscle, 
and the central nervous organs are the tissues most frequently affected . 
As before stated, interstitial as well as parenchymatous tissues may be 
involved. The cellular constituents of exudates and transudates are 
also liable to the change, and the liquid may thus present the appearance 
of an emulsion. 

Pathological Physiology. — Recent investigations tend to destroy 
the old theory that fatty degeneration results from a transformation of the 
protoplasm of cells into fat. Investigations have shown that the cells 
of many of the tissues and organs, notably glands, contain fat, and that 
this is undoubtedly derived from the blood, also that the fat in true 
fatty infiltration has the same origin. In so-called fatty degeneration 
the protoplasm is diseased and in advanced stages completely destroyed. 
This would seem to sustain the old view of direct transformation of pro- 
toplasm into fat; but the most accurate chemical investigations indicate 



RETROGRESSIVE PROCESSES 



91 



that this is not the only process. Further, when animals were poisoned 
with phosphorus and a fat foreign to the animal was administered the 
fatty organs contained the foreign fat. These considerations have led to 
a quite general belief that fatty degeneration results from an infiltration 
of fat derived from the blood and remotely from the fat deposits of the 
body or from food. The significant difference between fatty infiltration 
and fatty degeneration is that the former is a deposition of fat in otherwise 
normal cells as a result of excessive supply of fat, or possibly a lowered 
metabolic activity which normally disposes of fat, while the latter repre- 
sents a deposit of fat in a diseased cell, the disease inviting the deposition 
or greatly reducing the capacity of the cell to dispose of fat even in normal 
quantities. For these reasons the terms "fatty infiltration" and "de- 
generative fatty infiltration" have been suggested for the respective 
conditions. It seems certain that to some extent at least the granular 
and molecular fat contained in cells the seat of "fatty degeneration" 
represents normal fat of the cells which had previously been in some form 
of combination and invisible, but as a result the degeneration became 
free and visible. This view has been expressed by a number of pathologists 
and has some experimental support. 

In some experiments in which starving frogs were poisoned with 
phosphorus the direct conversion of protoplasm into fat seemed to have 
been demonstrated, but even in these experiments the glycogen of the 
liver may have been the source of the fat produced, and, besides, ob- 
jection has been raised against the chemical method relied on in these 
experiments. 

It would seem probable that both factors may be active in most cases, 
but Wells maintains that in kidneys and muscles the metamorphosis 
of intracellular fat is more important than absorption. In either case 
it is to be assumed that the enzymic power of the cells has been damaged. 

Fatty degeneration tends to cause secondary changes in the proto- 
plasm of the affected cell, or the degeneration which in the first instance 
underlies the condition tends to increase until the cell is practically 
destroyed. Cellular function is, therefore, eventually impaired or per- 
verted, but experiments have shown that considerable fatty degenera- 
tion of the heart muscle may exist without impairment of the heart's 
power (Romberg, Krehl). The same may be true of other organs. Mild 
grades, with preservation of the nuclei of the cells, admit of recovery; 
severe grades go on to total necrobiosis. 

Lipoid metamorphoses are found either as infiltrates or degenerations 
in cancer necroses, atheromatous blood-vessels, and syphilitic lesions. 
They were formerly considered fatty but it is now strongly suspected that 
they have to do with protein destruction. The lipoids are commonly 
found as cholesterol esters and appear as doubly refractile or cuboidal 
crystals under the polarizer. 

THE ALBUMINOID DEGENERATIONS 

The hyaline, mucoid, and colloid degenerations represent protein 
metamorphoses which are closely related. In typical instances they can 
be quite clearly differentiated from each other, and for the sake of clear- 
ness and convenience they will be separately described. It must be 



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A TEXT-BOOK OF PATHOLOGY 



understood, however, that the products are closely related substances 
whose chemical characteristics and relations are not clear, and which 
cannot in many cases be distinguished. 



Definition. — This term probably comprises a group of retrogressive 
processes characterized by the appearance of a clear, firm, homogeneous 
protein substance of obscure nature. It is probable that various proc- 
esses, defined as hyaline, may have entirely different characters. Cer- 
tain cases are allied to amyloid, mucoid and colloid metamorphoses, 
and some to coagulation necrosis. The hyaline change of epithelium 
of older authors is now, by general consent, classed as a mucoid 
transformation. 



Fig. 18. — Cylindroma showing hyaline metamorphosis about sarcoma-like nests. 

Etiology. — Hyaline degeneration occurs under the following patho- 
logical circumstances: in the muscles during infections and septic 
processes and following traumatism; in intoxications, as by lead; in inter- 
stitial hemorrhages and hematoma; in struma; in cicatrices; in the blood- 
vessels in old age, arteriosclerosis, or aneurysm; in all forms of arteritis, 
especially in vessels of the nervous system; in the endocardium and cardiac 
valves in all diseases affecting them; in the granulomata; in neoplasms, 
especially cylindromata and keloids; in the lungs in pneumonia; in the 
kidneys in nephritis; and in all conditions of coagulation necrosis and 
fibrinous exudation, for in these processes hyaline degeneration seems 
to be a factor. Very probably the process is not the same in all of these 
cases, but the similarity of appearance, staining reaction, and general 
pathological behavior prevents a definite differentiation. 



HYALINE DEGENERATION 




RETROGRESSIVE PROCESSES 



93 



Pathological Anatomy. — Hyaline change is not usually massive 
enough to be macroscopically appreciable. When so, the organ or tissue 
is enlarged, dense, and presents a pale, homogeneous, opaque appear- 
ance. Upon the mucous and serous membranes small collections may be 
readily seen, and may present either a pseudomembranous appearance 
or may occur as opaque plates upon or beneath the surface. Micro- 
scopically, there are three chief sites : (a) In the blood-vessels, where the 
degeneration may appear in the endothelium, beneath it, between the 
coats and fibers of the vessel, or surrounding the vessel. The wall is 
thickened, the lumen is narrowed or obliterated ; the endothelium may be 
loosened or in a state of proliferation. Perivascular hyaline change is 
well seen in certain tumors — cylindromata (Fig. 18). (6) In the inter- 
stitial tissues, as between the muscle-fibers, the hepatic cells, the renal 
tubules, in the reticulum of lymph-glands, in the retina, and in neoplasms 
and cicatrices. It may be uniform in distribution, but is more often 
irregularly clumped or may be in concentric whorls. In tuberculous 
foci the reticular fibrillse become swollen and gelatinous in appearance. 
They may swell to such a degree that the whole focus has a uniformly 
waxy appearance, the cells enclosed in the meshes meantime under- 
going complete necrosis. In scleroses, as in the liver, the newly formed 
connective tissue may assume a hyaline character, the fibers being so 
closely packed together and transformed that the mass has a homogeneous 
appearance, (c) Within the cells. This condition is probably limited 
to mesodermic cells. It may be seen in muscle and giant cells, and in 
endothelium, leukocytes, or wandering cells to a less degree. Whether 
the epithelial cells take part in this transformation in the coagulation 
necrosis of mucous membranes and in the production of casts in nephritis 
has not been decided. It has not been possible, in the intercellular or 
interstitial varieties, to decide whether the substance was formed there or 
deposited there; in the vascular form, and especially in coagulation necrosis 
and fibrinous exudations, it is probable that it is formed in loco. 

" Hyaline thrombi" cannot be distinguished in their appearance from 
hyaline masses elsewhere. Whether or not they are examples of true 
hyaline material is uncertain. 

Russell's Fuchsin Bodies. — These are round bodies, of variable size, 
situated within or between the cells of epithelial tumors or many normal 
tissues. They resemble hyaline material in appearance and staining 
reactions, especially in their affinity toward acid fuchsin. 

Unstained, hyaline substance has a glistening, waxy appearance; 
it is less translucent than amyloid. Typically it evinces an affinity for 
the acid anilin stains. Stained with van Gieson's mixture of picric 
acid and acid fuchsin, the hyaline substance takes on a brilliant red 
color. It may or may not take the fibrin stains; it often takes basic 
stains in a modified manner. In truth, the reactions of hyaline material 
are very uncertain and shifting: in many instances it can scarcely be 
distinguished from amyloid, and the change is then called hyalo-amyloid ; 
in other instances the product closely resembles mucin and the colloid 
substance. The cells of affected parts often show fatty degeneration or 
other alterations. 



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A TEXT-BOOK OF PATHOLOGY 



Seats. — The locations most often affected are the muscles, especially 
the recti abdominalis in typhoid or other fevers (the so-called Zenker's 
hyaline), the mucous membranes, the liver, kidneys, ovaries (corpora 
lutea in particular) and adrenal bodies, the cardiovascular system, the 
nervous system, the serous membranes, and the retina and choroid coats 
of the eye. The other locations are suggested in the discussion of the 
etiology. 

Pathological Physiology. — V on Recklinghausen believed it to be a 
coagulation of normal protein upon the death of the cells; this explana- 
tion is, however, insufficient. It appears more likely either that it con- 
sists of protein modified in loco by disturbed action of cells, or that it is 
a deposition by cellular carriers of insoluble material formed elsewhere. 
The exact nature of the transformation is entirely obscure; it cannot be 
held analogous to the coagulation of proteins by heat; nor to the pre- 
cipitation by metals or salts, since in these events the proteins are not 
usually rendered permanently insoluble in water and are in other ways 
clearly different. Hyaline material can undoubtedly be reconverted, 
absorbed, and removed. Its presence rarely compromises the paren- 
chymatous structures to an extreme degree. 

MUCOID DEGENERATION 

Definition. — Theoretically, this is the conversion of cellular pro- 
toplasm into mucin. Mucin is a glycoprotein which contains no phos- 
phorus, and which by virtue of its carbohydrate moiety reduces cupric 
sulphate in alkaline solution. Chondroitin sulphuric acid has been found 
in some mucins, showing the relationship of this albuminoid degeneration 
to amyloid infiltration. It is quite insoluble in water, but has itself a 
marked capacity for taking up water. It is very soluble in alkaline solu- 
tions, but is precipitated by saturations with most neutral salts. It is 
precipitated by acetic acid from solutions poor in salts; also by heat, 
alcohol, and many of the metals. It does not dialyze. The secretions 
from different classes of epithelium differ notably among themselves, 
and the pathological mucins differ still more. 

Etiology. — Mucoid transformation should be distinguished from 
hypersecretion of mucin. Hypersecretion is a common result of inflam- 
mation or irritation of all sorts; it is seen in the pulmonary, gastroin- 
testinal, and urinary mucous membranes, in the glands of Cowper, the 
gall-bladder, the salivary glands, in the antrum of Highmore, in the lac- 
rimal glands, and in the testicles. The product of the epithelium of the 
urinary tract and gall-bladder, usually called mucin, is more often nucleo- 
albumin. Mucoid degeneration, in the strict sense, occurs most frequently 
in mesoblastic tissues, the abnormal substance lying between the cells. 
It is in some way connected with inflammatory processes, as, apart from 
its occurrence in tumors, it is found only in tissues the seat of inflamma- 
tion. Any of the connective tissues of the body may be affected. Wide- 
spread myxomatous degeneration of the subcutaneous tissues may be 
seen in myxedema. In some cases of myxedema, scleroderma, and the 
other pachy dermic affections mucin has been extracted from the skin; 
other attempts in similar cases have failed. Neoplasms comprise the 
third group of conditions presenting mucoid phenomena. The trans- 



RETROGRESSIVE PROCESSES 



95 



formation occurs in sarcomata, carcinomata, fibromata, lipomata, chon- 
dromata, and especially in the myxomata, in which mucin is the essential 
element, while in the other growths it is an accidental and occasional 
transformation. In the epithelial tumors the epithelial cells themselves 
may be affected, or they may only supply the mucoid matter. 

Pathological Anatomy. — The gross appearances may consist in 
nothing but the appearance of the mucin. Upon catarrhal mucous 
membranes is a coat of thick, tenacious mucus, with or without con- 
gestion or other changes. In localities where the mucin becomes pent 
up it swell's markedly, dilates the containing spaces, flattens the epithe- 
lium (which may then atrophy), and later becomes converted into a 
simple albuminous fluid. Such a process is seen in the antrum of High- 
more, in Cowper's glands, in the salivary glands, in the gall-bladder, in 
the vermiform appendix, etc. ; in these cases the appearances are those of 
a cyst. In mucoid degenerations in the connective tissues the appear- 
ances are often not characteristic of mucin; the tissues are soft and 
elastic and tear easily. In tumors, cysts 
are usually formed along with diffuse 
mucoid infiltration. In cystic ovarian 
neoplasms the production is often mas- 
sive, and the substance is often peculiar 
in refusing precipitation by acetic acid, 
and has, therefore, been termed "pseudo- 
mucin." In myxomata the substance is 
usually much more dense. 

Microscopical Appearances. — In ca- 
tarrhal mucous membranes the goblet- 
cells are seen in excessive quantity. 
Only in extreme instances is the process 
accompanied by the death of the cell. 
The cells are much swollen, and the 
distal end is especially bulged out with its 
drop of mucin. There is usually a sub- 
mucous inflammatory reaction, and pus-cells containing mucoid material 
may be seen. In the connective tissues it is seen that the mucin lies 
between the cells and that the ground substance has disappeared — i. e., 
been converted into mucus (Fig. 19). The cells very rarely present 
mucous change, but are often degenerated in other ways. In tumors 
the change may occur in and between the cells and in the form of cysts, 
whose walls may or may not present a cellular lining. The blood- 
vessels are rarely affected. In all situations mast-cells may be seen, 
often abundantly. 

Mucin is best fixed with corrosive sublimate. As a rule, it elects basic 
stains. It stains only moderately with hematoxylin, but very well 
with methylene-blue and, indeed, with most of the basic anilin stains. 
Thionin and toluidin-blue are the best stains, giving it a purple-red color. 
These staining reactions are not entirely distinctive, and it is often im- 
possible to differentiate mucoid from colloid material, and even from 
hyaline and amyloid material. 




Fig. 19. — Myxomatous degenera- 
tion of a sarcoma, showing stellate 
cells separated by mucoid inter- 
cellular material (Karg and Schmorl) . 



96 



A TEXT-BOOI£ OF PATHOLOGY 



Seats. — Of normal epithelial tissues, the mucosa of the respiratory 
and gastro-intestinal tracts, the salivary glands, and the uterus are most 
often affected; any epithelium may, however, be involved. The con- 
nective tissues have been sufficiently considered. Of neoplasms, ovarian 
cysts, abdominal carcinomata, and mesoblastic tumors anywhere are 
most liable. 

Pathological Physiology. — Since the deposition of mucin seems to 
be excluded, the only explanation is to assume the conversion of other 
proteins into mucin. The causes and modus operandi are not clear; the 
fact, however, that in the cysts the mucin may be reduced to simple 
albumin shows the possibility of such transformations. 

Unless the disease is very prolonged, affected mucous membranes 
may recover. The connective-tissue forms do not of themselves threaten 
the life of the tissue; and the deposit is often removed by reabsorption. 
In neoplasms the degeneration seems an evidence of cell death. 

COLLOID DEGENERATION 

Definition. — This consists in the abnormal appearance of a sub- 
stance whose physical prototype is the colloid material of the thyroid 
gland. It is not precipitated by acetic acid or alcohol, does not take 
up water avidly, and is, therefore, much like the pseudomucin already 
noted. 

Etiology. — It occurs in goiters and in thyroid neoplasms, in the 
hypophysis cerebri, in the kidneys (some cases of congenital cysts) 
and the adrenal bodies, in the prostate and seminal vesicles, in the 
atrophic gastric mucosa, in cysts of the hps and larynx, and in the cervix 
uteri. Colloid transformation in neoplasms apart from those of the 
thyroid body is very rare. The natural and increased colloid of the 
thyroid gland, and sometimes that found in the hypophysis, contains 
iodin, associated with a globulin and a nucleoprotein. Because of the 
absence of iodin in other so-called colloid conditions, cancers and cysts, 
many authorities restrict the word "colloid" to the iodin-contain- 
ing kind of the thyroid, and call the homogeneous metamorphosis in 
cancers mucoid. Colloid is believed to be a direct product of altered 
cell metabolism, and, aside from the thyroid, is usually mucin, pseudo- 
mucin, or some other protein which has assumed a jelly-like form in a 
tightly closed space. There is no uniform organic chemical substance 
that may be identified as colloid. 

Pathological Anatomy. — Affected organs may be enlarged and may 
be hard or quite soft. On section, the colloid areas appear as yellowish- 
brown, translucent bodies; rarely they are arranged in large clumps. 
They' may be macroscopically invisible or, on the contrary, may form 
large cystic collections with thin, flattened walls. Colloid degenera- 
tion may be accompanied by serous transudation, due probably to 
vascular disturbances. The serous transudation seems to dissolve the 
colloid material, so that finally the cysts form compartments filled with 
a chocolate-colored fluid containing pus, blood, and crystals of choles- 
terin, sodium chlorid, and calcium oxalate. 

Microscopically, the material is found in the glandular acini, in 
the cells, and in the connective tissues (Fig. 20). There are often signs 



RETROGRESSIVE PROCESSES 



97 



of pressure, and, probably from the same cause, the areas are anemic and 
have a poor vascular supply. The arrangement is usually in balls or 
whorls, homogeneous as a rule, but often with concentric or radiating 
lines. The areas often intercommunicate, and extensions may be traced 
into the adjacent tissues. The cells usually show degenerative changes, 
and inflammatory reactions are often present. Crystals of calcium 
oxalate are common. Acid stains are usually elected, as in hyaline degen- 
eration. The indefiniteness of the reactions may make it impossible to 
exclude hyaline and mucoid changes. 




Fig. 20. — Colloid in the thyroid gland, showing masses of colloid matter in the gland 

acini (Karl and Schmorl) . 

Pathological Physiology. — This is obscure, but seems to be analo- 
gous to that of mucoid change. The substance is undoubtedly produced 
in loco. 

AMYLOID INFILTRATION 

Definition. — Amyloid deposits are nowadays, thought infiltrative, 
although formerly regarded as degenerative. Amyloid, a name given by 
Virchow because of certain reactions suggesting starch, is not a starch, 
but a glycoprotein, an abnormal combination of chondroitin sulphuric 
acid, such as is normal in tendon, with a protein. The exact chemistry 
is not known and the combination is believed to be due to faulty met- 
abolism in loco. It differs from most retrogressive changes in that 
it affects the interstitial tissues, and not the cellular contents. The 
presence of balls of amyloid within cells has been maintained by some 
authors. The names "lardaceous disease" and "lardacein" are used by 
some writers, denominations warranted by the gross appearance at least. 

Amyloid disease may be local or general, the latter being called 
" amyloidosis." 

Etiology. — The common conditions under which amyloid infiltra- 
tion arises are prolonged suppuration and ulceration. In tuberculosis, 
especially of the lungs and skeleton, particularly in cases of mixed infec- 
tion and in syphilitic ulceration, are found the conditions most favorable 

7 



98 



A TEXT-BOOK OF PATHOLOGY 



to its production. It occurs, however, in connection with ulcerations 
of various sorts, gastro-enteritis, and actinomycosis. Rarely it occurs 
under conditions of cachexia without suppuration, as in cancer, malaria, 
leukemia. Sometimes it is found without any apparent cause. 

Certain local " amyloid" formations (corpora amylacea) are probably 
in nowise connected with the general condition and, undoubtedly, are 
often entirely physiological. Their relation to amyloid disease is doubted 
by many, but they do give modified iodin and gentian- violet tests. 
It is said that they grow by deposit of crystals containing some protein. 

Pathological Anatomy. — In marked instances the organs are en- 
larged and their specific gravity increased. On section, the tissue is firm; 
the cut surface is smooth and neither contracts nor extrudes. The 
consistency varies with the coexistence and degree of fibrosis, fatty 
degeneration, etc. Amyloid substance is more inelastic than any other 
infiltrative material. The color of the organ is usually pale, but may 
obviously be altered by congestion, pigmentation, or fatty degeneration. 
The amyloid substance itself has a glistening, waxy, translucent appear- 
ance which is almost pathognomonic. This waxy appearance is not al- 
ways uniform. Slight or even moderate degeneration may not occasion 
macroscopical appearances; in fact, apparently quite normal tissues may 
be highly amyloid microscopically. The special appearances in various 
organs will be described in the appropriate chapters. 

Lipoid or actual fatty deposits are found associated with amyloid 
infiltration, especially in syphilitic conditions. They are either deposits 
from body fluids or arise from tissue degenerations in the vicinity. 

Microscopical Appearances. — The favorite seats are the outer surface 
of capillary blood-vessels and the intima and media of larger blood- 
vessels, the adventitia being rarely affected, the endothelium apparently 
never. The fixed connective tissues of the organs, elastic tissues, and 
basal membranes of glandular acini, or between them and the gland 
cells, are the parts affected, the wandering cells and leukocytes being 
rarely involved. Muscle cells are undoubtedly susceptible; but recent 
studies seem to show that glandular and lining epithelium is never 
involved. Such cells may, and often do, show fatty or other degenera- 
tions or necrosis, but the presence of amyloid substance within their 
protoplasm has not been shown. The substance appears as irregular 
clumps or streaks in the interstitial tissues, often compressing the cells 
and blood-vessels. It presents a glistening, homogeneous appear- 
ance. The cells usually present evidences of atrophy and other de- 
generations. In the renal glomeruli and in the Malpighian corpuscles 
of the spleen the appearances are perhaps most distinctive. Without 
staining, amyloid degeneration cannot always be distinguished from 
other degenerations; indeed, not always with staining reactions. The 
substance is highly resistant to bacterial decomposition and to diges- 
tion (see Plate 16, facing page 778). 

Reactions. — (See also below.) The gentian-violet reaction seems to 
be the most invariable. In sections of tissue fixed (preferably in 
alcohol) for microscopical study gentian-violet colors the normal tissues 
blue; the amyloid substance is a light pink or red. Iodin-green gives a 
similar red reaction. A mahogany-red reaction with Lugol's solution 



RETROGRESSIVE PROCESSES 



99 



of iodin is quite constant, but fails in the isolated amyloid bodies. It is 
easily obtained in fresh specimens freed of blood. The red color is 
changed to a blue by treating with sulphuric acid or chlorid of zinc. 

Seats. — In the order of frequency amyloid degeneration affects the 
kidney, liver, and spleen, then the larger blood-vessels, the intestinal 
mucosa, the lymph-glands, the skeleton, the adrenal bodies, and the 
heart. It rarely affects the pulmonary mucosa, the bladder and genitalia, 
the thyroid body, the voluntary muscles, and, apart from the local amy- 
loid bodies, the nervous system or the integument. 

Local Amyloid Formations. — These occur in the nervous system, 
especially in advanced years and in scleroses, grouped about the blood- 
vessels, and most marked in the posterior cord and in the brain; in 
the prostate gland; about inflammatory areas; in infarcts; in granulom- 
ata, especially syphilis; as tumor-like swellings in the upper air-passages, 
and in neoplasms. They present themselves as small round bodies 
which usually have a concentric arrangement resembling starch granules. 
They do not usually present the typical amyloid reactions; often they 
react more like hyaline substance, and, indeed, the blood-vessels of the 
affected part seem especially affected with hyaline change. Ribbert 
says the small vessels are curiously free from change. The neighboring 
lymph-vessels and glands are usually attacked. The special appear- 
ances and reactions of the amyloid bodies of the nervous system will be 
described in connection with Neuropathology. 

Pathological Physiology. — As stated, amyloid substance seems to 
be a combination of chondroitin sulphuric acid with a protein. It is 
composed of hydrogen, nitrogen, carbon and sulphur, and is insoluble 
in weak alkalies. Chondroitic acid is normally present in bones, carti- 
lages, and elastic tissue. It seems to have been shown that an amyloid- 
like substance exists in the elastic coat of the blood-vessels — perhaps 
a different combination of chondroitic acid. Our present knowledge sug- 
gests that amyloid substance is not entirely abnormal, but rather an 
abnormal combination of normal substances. It seems to result from 
protein alterations in connection with the pathological processes already 
detailed, having as a result the liberation of large amounts of chondroitin 
sulphuric acid. That bacterial influences are not necessary is suggested, 
though not proved, by the fact that amyloid change has been produced 
by long-continued aseptic suppuration induced by turpentine injection. 
Amyloid change is an infiltration, the constituents being deposited from 
the blood and assuming their peculiar characters locally, for amyloid 
is not found preformed in the blood itself. Possibly local cellular condi- 
tions favor the deposition by reason of a loss of power to dispose of the 
constituent substances brought by the blood. Hyaline degeneration 
seems at times a preliminary stage in the process. 

Amyloid degeneration interferes with functional activity by pres- 
sure upon the parenchyma and by vascular disturbances. By its situa- 
tion in and around the blood-vessels it may occasion thrombosis. Reab- 
sorption of amyloid substance is possible, as it has been known to occur 
when part of the diseased area has been extirpated. Such reabsorption 
does not, however, occur when extensive amyloid change exists. 



100 



A TEXT-BOOK OF PATHOLOGY 



GLYCOGENIC INFILTRATION 

Definition. — This condition consists in the presence of glycogen in 
cells which normally contain none, or the presence of an excess in cells 
which normally contain it, as in the liver, cartilages, muscles, leukocytes, 
in the embryo in all tissues, and in the uterus. The attempt has been 
made to separate glycogenic infiltration from a glycogenic degeneration, 
but the conversion of protoplasmic protein into glycogen has never been 
demonstrated. 

Etiology. — The condition is not infrequent. It is seen in the tissues 
in diabetes, especially in the kidneys (Heme's loop in particular), muscles, 
liver, and circulating leukocytes. It occurs in neoplasms, especially 
in malignant growths of mesoblastic origin, being rare in most car- 
cinomata. It may be said that the more cellular the tumor, the more the 
glycogen, except in carcinomata, where the amount is small and variable. 
In leukocytosis of different varieties the cells may contain granules of 
glycogen or a substance resembling glycogen, and similar granules may 
float free in the plasma (see Iodophilia). In purulent collections and in 
inflammatory areas the cells maybe markedly infiltrated. The infectious 
granulomata, however, seem exempt. The amylaceous bodies of the 
prostate are closely allied to glycogen. 

Pathological Anatomy. — Tissues rich in glycogen may present a 
hyaline appearance; usually there are no macroscopical alterations. 
Microscopically, the material is generally found within the cells; it may, 
however, be in the intercellular substance, and may be free in the plasma 
of blood or the fluid of exudates. It is commonly deposited as round 
balls, which may be concentrically striated. In fresh tissues it is soluble 
in water, but loses its solubility after fixation by alcohol, etc. Tissues 
to be studied for glycogen must be fixed in absolute alcohol, since watety 
solutions add a molecule of water to the glycogen and change it to sugar, 

CeHioOs -f- H2O = C6H12O6. 

Glycogen is stained brown by iodin, but the brown is not turned 
blue on the application of sulphuric acid. Ptyalin or amylopsin con- 
verts glycogen into sugar, with the loss of the color-reaction. 

The pathological physiology is obscure. In diabetes it is simply 
an expression of the general hyperglycemia. At the end of long exhaust- 
ing diseases glycogen may not be found in the cells. The cells are left 
swollen. In neoplasms and suppurations the collections are probably 
depositions. 

DROPSICAL INFILTRATION 

By dropsical infiltration is meant edema of the cells, the presence in 
cells of an excess of plasma. It may be considered as of two kinds: 
(a) Dropsical degeneration, a fine granular disintegration of the cyto- 
plasm preceding or associated with cloudy swelling, (b) Dropsical in- 
filtration, grosser collections of vacuoles or droplets of fluid disturbing 
the general architecture. This does not always occur in general dropsy, 
the fluid being between the cells and often compressing them to a 
marked degree. In other instances the cells take up the fluid. In burns 



RETROGRESSIVE PROCESSES 



101 



and pemphigus and in other skin lesions presenting vesiculation, and in 
various inflammations of organs, edema of the cells occurs. It is also 
a part of the degeneration termed " cloudy swelling." 

The cells are enlarged, often to an extreme degree, and they may even 
burst. The protoplasm sooner or later becomes cloudy and often 
presents degenerative changes — fatty metamorphosis in particular. 
-Vacuolation is frequently observed (Fig. 21). 




Fig. 21.— Dropsical infiltration of the epithelial cells of a carcinoma of the breast: a, 
Ordinary epithelial cells; b, b, dropsical cells; e, dropsical nuclei; d, enlarged nucleoli 
(Ziegler). 

The condition is probably a purely physical phenomenon in the 
dropsies. In the cutaneous lesions other factors are operative. The 
diffusion of water into the cell may be explained by a toxic disturbance 
of the internal chemistry with an increase of crystalloids which attract 
water. 

CALCIFICATION 

Definition. — Calcification consists in the abnormal deposition in 
tissues of earthy salts, without organization and the anatomy of bone. 
It may be considered as evidence of local or general senescence, but is 
never a primary process. The phosphates and carbonates of calcium are 
the chief salts concerned; oxalates, however, are often present; and the 
corresponding magnesium salts may be mixed with them. The best 
physiological examples are the senile change in the vascular apparatus 
and the formation of the brain-sand (acervulus cerebri). Calcification 
of the skeletal tissues is usually accomplished as a physiological process 
through the activities of special cells; this is an essential element 
in ossification. 

Etiology. — The deposition generally occurs in diseased tissues, 
especially in those the seat of vascular disorders. Local necrosis or 
fibrosis antedates intercellular calcification, and the process maybe 
accompanied by atrophy and absorption of certain cellular elements. 
In neoplasms, abnormal cellular conditions certainly predispose; but 
here, too, the vascular relations are of notable importance. Hyaline 
and fatty degenerations often precede or accompany calcification. 

In rare instances no local predispositions can be determined. Cases 



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A TEXT-BOOK OF PATHOLOGY 



of this kind occur in old age, and in these cases it is inferred that, owing 
to increased lime-resorption from the skeleton, the system is saturated 
to the point of precipitation (metastatic calcification). Similar super- 
saturation of the blood with calcareous matter may occur in cases of 
extensive disease of bones, and may lead to widespread deposition. It 
is noteworthy that the precipitation of the bone salts circulating in excess 
occurs most frequently where acid is excreted — lung, stomach, and kid- 
ney. Local anemia favors calcification. 

v. Kossa found that corrosive sublimate, acetate of lead, copper salts, 
iodin, and iodoform all are capable of producing calcification 
experimentally. 




Fig. 22. — Calcification of the kidney in bichloride of mercury poisoning. 



Pathological Anatomy. — Early in the process no macroscopical 
signs are apparent. On microscopical examination the salts are seen as 
fine .granules scattered through the intercellular substance. Cellular 
infiltration, however, is not uncommon, and in such instances the cells 
show more or less extensive nuclear and protoplasmic degenerations. By 
the coalescence of the granules larger, irregularly spherical bodies may be 
formed. These usually have a concentric arrangement (psammoma 
bodies). Definite crystals are rare, but may be seen. The next adjacent 



RETROGRESSIVE PROCESSES 



103 



tissue may present an opaque appearance. In certain localities, espe- 
cially the blood-vessels and serous membranes, calcareous plates are formed. 
The depositions may attain a surprising size, especially in the vessels 
and in neoplasms. The color of the deposits is usually white, grayish, or 
yellow; accidental pigments may, however, produce discolorations. On 
staining, the deposition takes up both carmine and hematoxylin, but 
exhibits no elective attraction for the anilin dyes. The salts are dis- 
solved by acids, best by hydrocloric acid; in the case of carbonates, with 
evolution of carbonic acid gas. Fibrosis, cellular necroses, and degen- 
erations can be demonstrated in the tissues by suitable methods. 

Seats. — It is in the cardiovascular system that the condition is 
of the most importance. It often occurs as a simple senile change, 
usually connected with an atrophy of the elastic tissues of the vessel walls, 
hyaline degeneration of the connective tissue, and general fibrosis. It is 
almost invariably an accompaniment of sclerotic endocarditis and arterio- 
sclerosis. In the endocardium the valves are most frequently affected; 
of the vessels, the aorta, the coronary arteries, and the cerebral vessels. 
The process is, however, often universal, and the splanchnic 
vessels and radial arteries seem very susceptible. It affects chiefly the in- 
tima and media. In the pericardium the deposition is uncommon without 
the^previous occurrence of pericarditis ; in adherent pericardium the heart 
may be literally enclosed in a calcified sac. In the myocardium calci- 
fication is usually interfibrillar, but may involve the fibers. Large col- 
lections may occur in the pituitary body, the meninges, and in the 
ventricular plexuses. It is common in the joints, uncommon in the pleura, 
rare in the peritoneum. In the muscles local formations are not rare, 
and usually occur at the seat of previous injury or irritation. In the 
lungs and liver it is not unusual in and around foci of necrosis due to vari- 
ous causes (tuberculosis, parasites, etc.). Cicatricial tissue often be- 
comes calcified, this being interestingly and significantly illustrated in 
the calcification of bronchial and mediastinal glands, the center of which 
not infrequently contains a bit of cheesy matter of an old tuberculous 
process. In the walls of cysts, in the biliary and urinary bladders, 
in the limiting wall of old abscesses and hematomata, in thromboses, 
about and within encysted parasites like trichina, and even in cutaneous 
scars calcification, as a crust or infiltration, is a common incident. 
Old infarcts, notably of the kidney, may show calcium deposit. The 
neoplasms most subject are the avascular tumors: uterine fibromata, 
fibromata in general, dermoid cysts, goiters, scirrhous carcinomata, 
tunors of the pituitary bodies, and especially neoplasms involving bones 
or cartilages. It may, however, occur in the most vascular sarcomata. 
The special term "psammoma" (q. v.) is applied to certain calcified neo- 
plasms. Lithopedia are the calcified fetuses of extra-uterine pregnancy. 
Apart from neoplasms, the most striking intracellular depositions are 
seen in the ganglion-cells in areas of softening and in the renal cells, 
following certain metallic poisonings (mercury). It is interesting to 
note that the intestinal epithelium, which normally secretes the larger 
part of the lime-salts discharged from the body, is rarely infiltrated by 
them. 



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A TEXT-BOOK OF PATHOLOGY 



Pathological Physiology. — It seems probable that calcium is car- 
ried in the blood, in the form of tribasic calcium carbon phosphate, by 
the agency of the proteins with an appropriate amount of carbon di- 
oxid. In both normal and pathological bone salt deposit there seem to 
be two forces at work', a local chemical condition favoring the precipita- 
tion of the least soluble crystalloids from the blood and the existence of 
some tissue element having an affinity for calcium. The latter factor 
has been said to be phosphoric acid by some writers and ascribed to 
physical factors, such as the concentrated colloid of cartilage, by others. 
The local chemical changes favoring calcium deposit are said to be a 
decrease in protein concentration when the tissue pabulum is thoroughly 
used up in loco, and increased alkalinity with decreased carbon dioxid. 
There is, however, some experimental evidence to show that the fatty acids 
formed in necrobiotic tissue combine with calcium to form soap, the com- 
bined acid later giving way to acid radicals of stronger affinity for the base, 
carbonic and phosphoric. It must not be forgotten that we are dealing 
with a secondary process in a tissue whose metabolism is not and has not 
for some time been normal. 

Calcareous deposits are probably never removed, but once formed, 
remain permanently. There is no doubt that they influence the 
adjacent tissues, causing degenerations. 

OSSIFICATION 

This term implies the deposition of lime-salts and other changes 
through the agency of osteoblastic cells. It occurs in cartilages and in 
tumors connected with the bones, cartilages, and periosteum. Ossifica- 
tion of the muscles may occur as a local process or as a widespread and 
progressive disease. (See Myositis Ossificans.) The salts are regularly 
deposited and are usually in masses between the cells. An accurate 
differentiation from calcification can in some instances be made only 
by the detection of osteoblasts after decalcification of the material. 
The essential difference lies in the fact that in ossification an attempt is 
made to reproduce the architecture of bone. 

URATIC INFILTRATION 

Deposits of urate of sodium in the cartilages and fibrous tissues of 
joints and in various . other situations occur in the course of gout. (See 
Disturbances of Metabolism and Diseases of Joints.) It is not known 
whether this occurs in normal or necrotic tissue, but such a deposit is 
not normal to cells. The urates occur as slender needles. In the kidneys 
of babies shortly after birth there occur deposits of urates, chiefly of 
ammonium, to which the name "uratic infarct" was formerly given. 
This gives a false impression, since it is merely a collection 
of urates of which the kidney cannot rapidly rid itself. 

Cholesterin deposits are not really infiltrations, but result from cell- 
ular degeneration, or some as yet undetermined cause. They appear in 
cysts and tumors, as in the thyroid and in atheroma, as flat, rhombic 
plates with an angular defect in one corner. With sulphuric acid they 
give first a red then a violet color. 



RETROGRESSIVE PROCESSES 



105 



Concrements.— There may collect in bodily or organ spaces, within 
the organs or their tubular entrances and exits, masses of inorganic 
matter. These are called concrements. By this is not meant that 
masses of foreign matter are introduced solely from without, like hair 
balls, but those whose components are recruited from the body fluids. 
Concrements may be started by a nucleus of desquamated covering or 
a product of inflammation, or by concentration, inspissation, or precipita- 
tion of some otherwise normal secretion or excretion. The first is 
exemplified by the collection of mineral salts around a bit of vesical 
mucosa that has been separated from the bladder wall or around amass of 
bacteria clumped in the gall-bladder by the bile, and floating in it. The 
second type is exemplified by collection of urates occurring as sand in 
the urine, with either clumping or growth by accretion. The 
so-called fecal stones arise by stagnation and inspissation of feces, with 
later accumulation of earthy salts. All stones probably have some organic 
matter in them either as a nucleus or caught in their growth. Small 
foreign bodies may penetrate viscera and cavities and form the nucleus 
of a stone. The chemistry of calculi varies with their origin. (See 
Urinary, Biliary, etc.) It has been suggested that the word "calculi" 
be restricted to bodies arising, from precipitation of glandular secretion, 
and the word " concrements" to the deposits of calcareous matter locally 
in visceral passages, leading to the formation of solid masses. This may 
be convenient, but is apt to lead away from the thought that a nucleus 
of some sort is necessary for concrements. 

PIGMENTATION 

According to the origin and variety of the pigments, pigmentations 
may be divided into four groups: 1, those in which the pigments are 
derived from external sources; 2, those derived from the hemoglobin; 
3, those derived from the bile; 4, those derived from cellular activity 
within the organism. 

Pigmentation from the Exterior 

Of the first group, those caused by entrance of foreign bodies through 
the air-passages are the most important. The condition now generally 
termed pneumonokoniosis is commonly a disease of occupation. 
Coal, iron, and stone are the most frequent foreign substances inhaled. 
Vegetable particles, as grain-dust and textile fibers, and animal hairs 
and furs, are not uncommonly the cause of such pigmentations. Corre- 
sponding to the agent, there are such terms as " anthracosis " (coal-dust- 
pigmentation), "siderosis" (iron), '" calcic osis" (stone), etc. (Fig. 23). 
Inhaled substances probably do not reach the alveoli, but are caught by 
the bronchial cellular cilia. In part they are coughed up or otherwise cast 
off with the bronchial secretions; in part they penetrate the bronchial 
walls or are carried by phagocytic cells into the submucosa (Plate 1, Fig. 1). 
They may become deposited in the latter situation, or may be carried 
in the lymphatic circulation to the peribronchial and mediastinal glands, 
the fibrous tissue of the lung, or the subpleural tissues. In rare instances, 
supposedly by rupture or inflammation of a lymph-node, the pigment 
finally reaches the general circulation, following which it is deposited 



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A TEXT-BOOK OF PATHOLOGY 



largely in the spleen, liver, intestinal mucosa, and kidneys. In such 
cases it shows a periarterial deposition in the secondary location. 

Some investigators have attempted to explain anthracosis of the lungs 
by absorption of coal particles through the alimentary tract. They 
assert that the particles pass through the abdominal lymph-nodes, up 
the posterior chain into the mediastinum, and thence to the lung. They 
would use this reasoning also to explain the course of infection in pul- 
monary tuberculosis. The theory is not widely accepted. 




Fig. 23. — Tuberculosis of the lung, showing anthracotic pigmentations in'the lower part. 

Pigmentation through the alimentary tract is well illustrated by 
argyria following the excessive ingestion of soluble salts of silver. 
The depositions seem to consist of a reduced form of a silver albuminate. 
In the skin the pigment lies directly under the epithelial layer, between 
the cells, and in the intercellular tissue and lymph-spaces. The gastric 
and intestinal walls are deeply affected. The liver and kidneys are usu- 
ally involved; in the former the deposition is periportal, in the latter the 
glomeruli and the corticomedullary boundary contain the pigment; 
in both the cells are free. Among the rarer sites are the choroid plexus, 
the various glands of the body, and the walls of the blood-vessels. 

Pigmentation by cutaneous absorption apart from tattooing is prob- 
lematic; it has been alleged to occur in workers in copper. 

Hematogenous Pigmentation 

This concerns the deposition of pigments derived from the hemo- 
globin, of which there are two groups, the siderous and the non-siderous 
When the blood coloring matter goes to pieces the first stage is the separa- 
tion of its principal constituents, globin and hematin, from the latter 



RETROGRESSIVE PROCESSES 



107 



of which pigments are derived, two main groups being recognized; iron- 
bearing or hemosiderin, and non-iron-bearing, hematoidin. In the course 
of time the siderous pigments may lose their iron. Probably all forma- 
tion and further elaboration of these pigments are the result of specific 
cellular activities. Two groups of hematogenous pigmentations may be 
distinguished: (1) those in which hemolytic agents act in the circulating- 
blood or the associated organs, and (2) those in which the reductions 
occur locally. 

(1) To the first group belong the general hemolyses. In pernicious 
anemia and leukemia, in malaria, in severe cachexias, in occasional 
infectious and septic processes, in poisonings (as by pyrogallic acid, chlo- 
rates, arseniuretted hydrogen, by some mollusks, by pyridin and toluyl- 
endiamin, etc.), the hemoglobin is set free in the circulation. It is 
promptly excreted by the kidneys, and to a limited extent by the intes- 
tines; much is converted into bile in the liver, some little passing into the 
bile unchanged. A certain amount is reduced by the tissues (apparently 
by the liver) to the two before-mentioned series of pigments, which are 
then carried in the lymphatic and vascular circulation, and by means of 
cellular carriers are deposited in various places. As time passes, these 
pigments seem to become reduced, the iron being largely excreted by the 
intestine and the remainder by the kidneys as urobilin. In the liver the 
depositions are mainly in the periphery of the lobule; in the spleen, in 
the region of the follicles, and especially in the endothelium; in the kidney 
the most marked collections' are in and about the glomeruli and the 
tubules. In all tissues the depositions are both intercellular and intra- 
cellular; the cells may either take up pigment or have it deposited in them. 

Hemochromatosis. — Von Recklinghausen first described under this 
name a condition in which iron-containing pigment is deposited in the 
epithelia of the abdominal glands, especially the liver and pancreas, and 
iron-free pigment in the smooth muscle-fibers of the intestines, and the 
walls of blood-vessels and lymph- vessels, as well as in connective tissues. 
He found cirrhosis of the affected organs associated with the pigmenta- 
tion. Later a form of widespread pigmentation of the same character 
and involving the structures named, as well as other organs, and notably 
the skin, and attended with glycosuria, was described by French writers 
under the name of diabete bronze. In this condition there is pronounced 
cirrhosis of the liver and pancreas, and the diabetic association is at 
tributed to the involvement of the latter organ. Cases without pancre- 
atic cirrhosis of a certain grade or kind are unattended with diabetes. 

Alcoholism, cachexia, and suppositious toxemias of other sorts have 
been regarded as of etiologic importance. The pigment is certainly of 
hematogenous origin, and is believed to be due to an altered metabolism 
in pigment-carrying proteins. The deposits in the cells cause degenera- 
tion and death of the latter and consequential cirrhosis. 

The appearance of organs with marked hematogenous pigmenta- 
tion varies with the variety and stage. A rusty-red color is the usual 
early appearance; later a brown, then a greenish, color may be pro- 
duced, and finally a dark blackish brown. The association of jaundice, 
which is common, alters appearances very much. 

(2) The two chief causes of local pigmentation are thrombosis and 



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A TEXT-BOOK OF PATHOLOGY 



interstitial hemorrhage and coagulation; local pigmentation is well seen 
following a bruise and most hemorrhagic infarcts leave behind them for 
a long time a discolored area due to hematoidin deposit. The 
pigmentations seen in the indurations resulting from prolonged venous 
stagnations and congestions are of analogous origin . Thus f or example may 
be explained that so-called heart failure cells (Plate 1, Fig. 2) seen in the 
lungs, and also in the sputum, of cases of cardiac decompensation with 
pulmonary congestion. The continued presence of blood in the small 
vessels is followed by local hemolysis and the granules of pigment are 
taken up, by alveolar epithelium and wandering cells, as yellowish brown 
granular masses. 

Under any condition of stagnation or the local accumulation of blood, 
the hemoglobin is diffused from the blood-cells' and a portion passes 
directly into the plasmatic circulation and is carried away to be eliminated; 
soon, however, the area becomes walled off and the two sets of pigments 
are then formed within. The siderous pigments are most frequently 
seen in small lesions and at the periphery of large ecchymoses ; the hema- 
toidin series is most prevalent within the cystic contents. The pigments 
change in color (the color changes in a bruise are due to this), and finally 
become a brownish amorphous matter, which in turn disappears. Pha- 
gocytic cells take up all forms of the pigments (Plate 1, Fig. 2) and carry 
them to various parts of the body, especially to the liver, hematopoietic 
organs, intestines, and glands; the depositions in them are known as 
pigment metastases. 

The distinctive reactions of the various pigments are not well known. 
Of hematin and hemin it is known that they are insoluble in water, alco- 
hol, and ether; slightly soluble in weak acetic and mineral acids; easily 
soluble in chloroform and in weak alkalies, from which solution they are 
precipitated on the addition of lime- or baryta-water. Hematoidin 
differs from these in being somewhat soluble in ether, but insoluble in 
weak acetic acid, and gives with strong nitric acid the spectral play of 
colors. Apart from the iron reactions little is known of hemosiderin. 
The iron is best demonstrated by its conversion into the sulphid by means 
of ammonium sulphid, or by the Prussian-blue reaction with weak hydro- 
chloric acid and potassium ferrocyanid (Perls' test). 

Microscopically, hematogenous pigment presents three chief appear- 
ances: small needles, rhombic crystals, and amorphous masses or fine 
balls clumped together (Plate 1, Fig. 3). The first two forms are very 
rarely seen within cells, the last form commonly. The colors vary from 
a pink-red to a deep rubin, from pale yellow-green to a deep brown or 
absolute black. 

Hepatogenous Pigmentation 

Pigmentations derived from the bile are due to bilirubin (isomeric 
with hematoidin) and its oxidation product biliverdin. Jaundice ordi- 
narily is of hepatic origin, but late observations would seem to indicate 
that bilirubin can be formed in the body without the action of the liver. 
The importance of this is not yet understood. Jaundice can also appear 
when a great hemolysis occurs, for if too much hemgolobin be thrown 




Fig. 1. — Phagocytic cells of the bronchial secretion (sputum) containing black particles 
of dust and carbon; the cells on the right are stained with methylene- blue (Jakob). 




Fig. 2. — Phagocytic ceils of the sputum containing blood-pigment, from a case of cardiac 
congestion of the lungs (Jakob). 




Fig. 3. — Hematoidin crystals from an old hemorrhagic focus (Jakob). 



RETROGRESSIVE PROCESSES 



109 



upon the liver, all the bilirubin cannot be discharged with the bile and 
is reabsorbed. 

The presence of bile or its salts in the blood occurs as a result of ex- 
ternal obstruction to the bile flow, or of internal mechanicochemical 
conditions favoring abnormal retention. The bile passes into the blood 
mostly by way of the lymph-channels, but may go into the vessels directly, 
as in cases of acute yellow atrophy. The bile-salts and pigments are 
both in the blood in icterus and are responsible for some toxic effects, 
such as degeneration of endothelium with hemorrhage and depression 
of the central nervous system. In addition there is a decided lengthening 
of the coagulation time, possibly due to a combination with calcium 
salts, and a lowering of the antibacterial properties of the blood. 

The deposition of these pigments may be either in solution in the 
tissues, in granular precipitations, or in crystals (needles and rhombic 
plates) . The cerebral substance alone seems never, except in the new- 
born, to be pigmented. The liver, skin, mucous membranes, the end- 
arteria and other serous membranes, and the glandular and fatty tissues 
are especially susceptible. The color is first yellow and gradually deep- 
ens to a deep olive, the urine presenting similar transitions. The lacri- 
mal and salivary glands, the mammae, and the intestinal mucosa seem 
to be able to keep the pigment from passing out with their secretions. 
The ocular fluids are colored. 

The pigment in solution saturates the tissues. The granular pig- 
ments, yellow, brown, or greenish in color, may be seen in the cells or in 
the interstitial tissues; the crystals, yellow or red in color, are usually 
extracellular. The pigment displays the spectral play of colors on con- 
tact with strong nitric acid, and is turned green by weak tincture of iodin. 

A special form of deposition is the bilirubin infarct in the urinary 
tubules. These are seen in severe jaundice of the newborn, but may occur 
in deep icterus of adults, as in acute yellow atrophy. 

Metabolic Pigmentation 

The pigmentation derived from cellular activity may be properly 
termed " metabolic." We know isolated facts about the different forms, 
but there is little systematic fundamental knowledge. Two facts, how- 
ever, seem clear: that these pigments are formed by migratory and resi- 
dent pigment-building cells, which with leukocytes and plasma cells 
accomplish the transportation and deposition of the pigments; and that 
hemoglobin is in some way or other the raw material for their manu- 
facture; some authors, however, think that protein under the influence 
of ferments produces these metabolic pigments, of which melanin is an 
example. This is an iron free, sulphur containing body. 

The manifestations may be local or general. Among the former 
are the pigmentations of nevi and moles, of pregnancy, of the corpus 
luteum, freckles, some scars, certain skin diseases, as chloasma and 
xanthelasma, of the lesions secondary to some cutaneous parasites, 
etc. A special local type is that seen in tumors, notably in melanosar- 
comata. Lipomata and sarcomata (chloromata) may be analogously 
affected, j 



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A TEXT-BOOK OF PATHOLOGY 



Among the general pigmentations are those of Addison's disease, 
of certain severe anemias and cachexias, of tuberculosis of the peritoneum, 
intestines, and retroperitoneal glands, of abdominal neoplasms, and of 
senility. 1 The cases associated with abdominal lesions are held to be con- 
nected with disturbances of the. adrenal bodies or of the chromaffin sys- 
tem, which has been considered to have control of pigment formations. 

Odchronosis is a black pigmentation of cartilage and related tissues, 
sometimes including fibrous tissues, and on occasion associated with 
melanuria. It probably belongs with the metabolic pigmentations, and 
has been ascribed to the action of a tyrosinase upon its related substance. 




Fig. 24. — Hemosiderosis of the liver. 



The metabolic pigments are very varied, and a detailed discussion 
of them here would be unprofitable. They may have a high percentage 
of sulphur and may or may not contain iron. They are commonly 
deposited in and between the cells as granules, but may be crystal- 
line. They do not give a play of colors with nitric acid, and have varying 
solubility. 

NECROSIS 

Definition. — Necrosis may be defined as the death of tissues. 
The death of individual cells is termed necrobiosis; death of tissue en 
masse, usually accompanied by putrefactive changes, constitutes gan- 
grene. 

Etiology. — All classes of cellular death may be brought under 
four etiological groups: 1, those due to nutritional and circulatory dis- 
turbances; 2, those due to trophic disturbances; 3, those due to poisons 
— animal, vegetable, bacterial, and inorganic; and, 4, those due to trau- 

1 The greenish black pigmentation frequently seen at postmortem is pseudo- 
melanosis and is the effect of decomposition; it is probably a combination of hydrogen 
sulphide and blood pigment. 



RETROGKESSIVE PROCESSES 



111 



matism, employing the term in its broadest sense. It has been at- 
tempted, without success in our opinion, to class the trophic necroses as 
identical with those due to circulatory and nutritional disturbances; 
similarly, the poisons and tramatism have been considered as acting 
only through the circulatory and nutritional paths, but it seems evident 
that in the light of our present knowledge the four groups are to a greater 
or less degree distinct. 

The various causes do not produce constant types of necrosis, but 
occasion one form in some cases, another in other cases. Prominent 
among these varying circumstances are the native health of the tissues 
and their vital resistance, the circulatory relations of the part involved, 
the activity and duration of the causal agents, the age of the subject, 
the presence of other diseases, the temperature of the tissues, etc. It 
will, therefore, be better first to consider collectively the causes of necro- 
sis, and subsequently detail the varieties of it. There can be no doubt, 
however, that in the direct forms of necrosis the results are to a marked 
extent individual to the agent; for example, cells killed by the action of 
acids, alkalies, and metallic salts present appearances quite characteristic 
of each. 

Circulatory Derangements. — The circulatory disturbances include 
many conditions. Acute and chronic ischemia, however produced — 
by embolism, thrombosis, arteriosclerosis and atheroma, by extra- 
arterial pressure, by cardiac weakness or by arterial spasm, as in Ray- 
naud's disease and perhaps in ergotism — are important conditions. 
Venous stagnations are responsible for many instances. Actual stasis 
due to mechanical obstructions or such poisonings as produce coagula- 
tion is a rare cause. Heat and cold act partly by circulatory disturb- 
ances. Among the general disorders of circulation and nutrition may 
be mentioned the anemias, the cachexias, senility, and certain metabolic 
diseases, such as diabetes. In these conditions there is much probability 
that poisoning by metabolic products plays an important part. 

Trophic Derangements. — Forms of necrosis due to trophic dis- 
turbances are well illustrated by bed-sores (decubitus), myelitic cystitis, 
the ulcerations seen in trigeminal neuritis, and the arthropathies. These 
forms of cell death cannot be brought under the circulatory, toxic, or 
traumatic classification. They can be explained only by the assumption 
that the biological mechanism of the cell is disturbed, and that in conse- 
quence death occurs. 

Intoxications. — -The group due to poisons is very extensive and the 
particular subdivisions numerous. The toxins of bacteria furnish many 
examples of direct necrosis, and act indirectly in cases which seem circu- 
latory or traumatic, though they are not really so, since these factors 
only lower the resistance of tissues, which then become susceptible to 
bacterial action. Experimentally the most exquisite forms of cell 
degenerations and necrosis can be produced by the injection of toxins or 
analogous substances like ricin and abrin. The alkaloids possess marked 
power in the production of necrosis. Acids, alkalies, metallic salts, and in- 
numerable other chemical substances may produce direct necrosis, or 
indirect necrosis by the preliminary production of degenerations. The 
same substances often cause both circulatory and mechanical disturbances, 



112 



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A TEXT-BOOK OF PATHOLOGY 



which augment their direct effects. Heat and cold act like chemicals; 
heat alters the properties of proteins; cold affects the fluids rather 
than the protoplasmic substances; both also induce marked circulatory, 
disturbances. 

Mechanical Agents. — The mechanical causes of necrosis are many 
and varied. Pressure per se may cause the death of cells, but is often 
aided by the circulatory disturbances which it occasions. That tension 
causes necrosis is an old surgical truth, well illustrated by the results 
of collections of exudates below the periosteum and by the results of 
strangulations. The pressure of calculi, concretions, enteroliths, and 
exostoses may cause important necrotic processes. Circulator dis- 
turbances often are a very active factor — indeed, many forms of trau- 
matism act solely through them. 

Inflammation, whatever its original inception, may become so ex- 
treme as to lead to necrosis. Necrosis, on the other hand, often leads 
to inflammation, the dead cells constituting the primary irritants. 

All forms of necrosis are accompanied to a greater or less extent 
by the various degenerations. In particular the cellular alterations 
are constantly present, and constitute the evidences of morbific action. 
The changes are due to disturbances of cell chemistry, among which 
enzyme action is, of course, the most important. (Reference will be 
made below to the cellular changes.) 

There are several general forms of necrosis which, however produced, 
have a sufficiently distinct character to warrant separate descriptions. 
Theyare coagulation necrosis, liquefaction necrosis, caseation, fat necro- 
sis, hemolysis, and gangrene. 

The cell, being the unit of structure, must needs be the particulate 
factor in the grosser appearance of necrosis, and anatomical or chemical 
changes have their origin in it. It so happens that a series of events 
takes place, however not necessarily always in the same order, which 
characterize necrobiosis and they can be conveniently studied by dividing 
them into nuclear and cytoplasmic. Anatomical changes are perceived 
principally by the reaction of cells to fixatives and stains while chemical 
processes are discovered by stains and reactions. The causes of necro- 
biosis are those given at the head of this subdivision. 

The first appearance of a dead cell is as if a coagulation had taken place 
within the cytoplasm, a condition in all probability, due to the precipita- 
tion of fibrinogen by prothrombin within the cell; changes of osmotic 
tension permit the fibrinogen to seep into the cell. The microscopic 
picture is not greatly altered from the normal save for a tendency of the 
cytoplasm to adopt more than one stain clearly thus giving a blurred or 
variegated appearance, hyperchromatosis. The nucleus at this time may 
contract and stain deeply (pyknosis), leaving a clear zone about it, 
or it may break up into irregular chromatic masses or fragments (karyor- 
rhexis) ; in place of this, a thinning and paling of the nucleus sometimes 
occur (karyolysis). While those things are going on, the cytoplasm is seen 
to break up or be extruded in small particles in pseudopodia from the cell 
margin. The disintegrated proteins gradually undergo solution and the 
identity of the cell ceases. 

The normal cell retains its form and chemistry by a constant supply of 



RETROGRESSIVE PROCESSES 



113 



pabulum from the serum so that when this is stopped by bodily death 
or obstruction to local circulation, food stuffs and the chemical reaction 
of the blood are withdrawn. The alkalinity and antiferments of the blood 
serve as controls of the internal chemistry of the cell and the absence of 
these permits in the first place, a reversal of the normal osmotic flow and 
then an activation of cell enzymes. The latter are principally proteolytic, 
acting best in an acid medium, and, as the nuclei are acid, being composed 
of nucleoproteid, they attack it when the alkalinity of the blood is 
withdrawn. Any acids formed by putrefaction will of course hasten 
this process anywhere in the vicinity. 

Thus necrobiosis is essentially a process of autolysis, or self digestion, 
and is perhaps the same process nature uses to rid herself of cells for which 
there is no further use. Certain modifications, too complicated to 
discuss in a book of this size, may be responsible for the condition we 
know as cloudy swelling, hyaline degeneration and the like. There are 
certain peculiar formations within leucocytes, tumor cells and even 
circulating mononuclears, that have been variously called inclusions, 
altered mitachondria or ferments, that in all probability are of the 
nature of alteration in staining reaction due to intracellular cleavage 
by action of enzymes from the cell or outside, the result of changes in 
osmotic pressure or the reaction of the blood. To this group belong 
Russell's fuchsin bodies, chlamydozoa and the like. 

COAGULATION NECROSIS 

Definition. — This is defined as that form of death of tissue in 
which the protein suffers a change similar to or identical with coagula- 
tion. It is seen only in those tissues which are rich in proteins, and 
possibly is due to coagulation of some of these by ferments set free by 
cell necrosis. The process is partly at least a species of fibrin formation, 
and is allied to hyaline degeneration. It may be chemically distinct 
from the coagulation of inflammatory exudate, as fibrin is not always 
demonstrable. Physically the two are almost exactly the same. 

Etiology. — The causes of this condition are those above detailed 
for necrosis in general. Circulatory disturbances, except thrombosis 
or infarctions, play a minor role here. Chemical irritants and high 
temperatures frequently produce it. Bacterial poisons are very prone 
to produce it, especially those elaborated by the pyogenic bacteria, 
the tubercle bacillus, and the diphtheria bacillus. About every abscess 
is found more or less coagulation necrosis; it is one of the early changes 
in tubercles and the fundamental element in the production of pseudo- 
membranes. All exudates and transudates are liable to coagulation. 

The serous and mucous membranes are most susceptible; next the 
muscular tissues (often the myocardium). 

Pathological Anatomy. — The tissue has a glazed, opaque, waxy 
appearance, and is firmer and paler than normal. In later stages the 
color becomes gray and the tissue inclines to soften. Microscopically 
it is seen that there is an exudate which has been fixed in the tissues; 
fibrin is seen (with suitable stains) in the form of granules and fibrils. 
In addition to the fibrin there is more or less homogeneous matter 

8 



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A TEXT-BOOK OF PATHOLOGY 



(fibrinoid) which does not react to stains like fibrin, but which is never- 
theless closely allied to that substance. The cells soon lose their elec- 
tion for stains. Early in the process the nuclei may stain faintly 
and present a homogeneous appearance ; later the cell disintegrates com- 




Fig. 25. — Embolic abscess of the pancreas. The darker area in the center represents 
closely packed staphylococci, filling a blood-vessel and invading the surrounding tissues. 
The light area around this represents cellular necrosis. The peripheral darker zone shows 
abundant invasion of leukocytes. The extreme periphery of the illustration shows pan- 
creatic tissue little altered. 

pletely (Fig. 26). In muscles the striations disappear; and in the car- 
diac muscle the intercellular cement substance seems to be dissolved, 
for the cells often lie separated and present vacuolation and fragmenta- 
tion. Pus, leukocytes, and red blood-cells in the affected areas all suffer 




Fig. 26. — Coagulation necrosis of the hepatic cells in a case of puerperal eclampsia (Karg 

and Schmorl). 

the fate of the fixed tissue. The blood-vessels at the margin of the area 
are seen to be thrombosed. In the kidneys the tubules may contain firm 
casts. 

Morbid Physiology. — Many chemicals cause coagulation by 
direct action. In the larger number of instances, however, it must be 
assumed that the fibrinogenetic substances which bring about the 



RETROGRESSIVE PROCESSES 



115 



coagulation of the proteins are derived from the necrobiotic cells in the 
area or are carried thither by the lymphatic cells. There is consid- 
erable evidence that bacterial products may act fibrinogeneticaHy. It 
has been contended that coagulation necrosis is simply a species of in- 
spissation of the tissues. This is certainly not the case. 

An area of coagulation may be cast off by the process of ulcera- 
tion, may undergo liquefaction, caseation, or suppuration, may be 
encysted, and apparently may be dissolved and reabsorbed. The 
area of the disease may finally be converted into scar-tissue by secondary 
regeneration. More or less complete loss of function results from 
this form of necrosis. 



LIQUEFACTION NECROSIS 

Definition. — This change consists in the death of tissue with colliqua- 
tion. It may be divided into primary and secondary forms. Second- 
ary liquefaction necrosis is the form in which other varieties of necrosis 
or degeneration are followed by liquefaction. Thus, areas of coagulation 
necrosis, cheesy necrosis, and of inflammation, gangrenous tissue, and 
tumors may become liquefied. 

Among the special forms may be mentioned vesicle formation and 
the softening of caseous tuberculous lesions. A very frequent seat of 
liquefaction necrosis is the central nervous system, where the condi- 
tions are unfavorable to coagulation, so that liquefaction here follows 
pathological conditions which would elsewhere produce coagulation. Cir- 
culatory disturbances, traumatism, and intoxications all cause soften- 
ing in the central nervous system; the peripheral nerves are much less 
susceptible. 

Pathological Anatomy. — In the early stages the tissue is softer 
than normal and very rich in fluid. Later, when the solution of the 
fibrillar tissues is advanced, the area becomes filled with a liquid of 
greater or less consistency, depending upon the tissue involved. The 
cells in the area are seen in all stages of degeneration; later, nothing but 
detritus is visible. In some instances, instead of becoming more and 
more fluid, the exudate undergoes coagulation. The color may be 
white, from the presence of an emulsion of fats; yellow, from fats and 
pigments; red and brown, from the presence of blood-pigment; and 
deeply colored when jaundice is associated. 

The process consists in the infiltration of fluid into tissues and the 
more or less complete solution of the tissue elements in it. It has been 
compared to the alterations of proteins by digestion — a reasonable de- 
duction, since the solution of the tissue or infiltrate occurs by digestive 
ferments. Should the process be of bacterial origin, the enzymes of 
the organisms are added to those of the infiltrative cells. Should bac- 
teria be absent, the ferments are freed chiefly after disintegration of the 
cells. (See Autolysis.) 

Areas of liquefaction may discharge their contents, may coagulate, 
may be reabsorbed, encysted, or, in uncommon instances, organized 



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A TEXT-BOOK OF PATHOLOGY 



CASEATION 

This is the crude name applied to a complex process whose product 
has a cheese-like appearance. 

The condition is most frequently seen in connection with tubercu- 
losis, although it is found in the other granulomata, and also in other 
pathological processes. The preliminary conditio sine qua non of casea- 
tion is coagulation necrosis. The modern view of the origin of casea- 
tion seems to be that it is a failure of an infiltrate to undergo complete 
liquefaction necrosis because the enzyme-bearing leukocytes are not 
attracted, and such enzymes as may be present are inhibited by the un- 
saturated fatty acids of the tubercle bacilli. Anemia of caseous areas, 
tuberculous or other kinds, plays a large part in the incomplete softening. 
Caseous matter is composed of coagulated protein and fat in various forms. 
Secondary infection brings blood-serum, which dilutes the enzyme- 
inhibiting soaps. 




Fig. 27. — Large tubercle of the lung, showing cheesy necrosis. 



The early tubercle, before the occurrence of softening, has an appear- 
ance like that of cheese, but is less homogenous and more granular 
(Fig. 27). A form of caseation quite similar in appearance occurs in 
pneumonia, in tumors, and especially in syphilis. Soft caseation is 
usually coagulation necrosis advanced to liquefaction, together with 
fatty metamorphosis, so that the appearances are those of soft, creamy 
cheese. The liquefaction necrosis of the central nervous system may 
present similar appearances. 

Microscopically, the tissues in caseation show no cells preserving 
their staining reactions; everything is converted into debris. Around 
the affected area is usually found a zone of coagulation, of inflammation, 
or both. 

Tissues that have undergone caseation may be cast off, reabsorbed, 
or encysted; resolution is not possible. Calcification is a frequent 
termination. 



RETROGRESSIVE PROCESSES 



117 



FAT NECROSIS 

This term is now used to designate a peculiar type of necrosis to 
which the fatty tissues are subject, and is distinct from ordinary fatty 
metamorphosis. In human beings it is seen almost exclusively in the 
abdomen, abdominal walls, and subperitoneal fat. In nearly all in- 
stances it appears in connection with pancreatic disease — cysts, tumors, 
obstruction to the duct, and the various forms of acute pancreatitis. 
In rare instances the pancreas has not seemed especially diseased. In 
one case known to one of us of hypertrophic cirrhosis of the liver the 
omentum was affected, while the pancreas showed nothing but a moder- 
ate degree of fibrosis. 

The affected areas are white in color, usually not larger than a pea ; 
they may be soft or quite gritty. Macroscopically visible inflamma- 
tory reaction may or may not surround them. On microscopical exami- 
nation crystals of the fatty acids may be seen, together with more 
abundant crystals of a combination of lime with the fatty acids. This 
combination, it appears, is not a primary feature in the necrosis, suggest- 
ing that the fatty acids are first set free and then unite with lime-salts. 
In experimental work by Hildebrand, Williams, and Flexner it seems to 
have been shown that the typical condition may be the result of direct 
action of the fat-splitting ferment of the pancreatic secretion. It is certain, 
however, that in some cases of pancreatic cysts containing steapsin no 
fat necrosis has occurred. Bacteria have been supposed by some to be 
the essential agents causing the change, but this has not been 
demonstrated. 

H. Gideon Wells, after quite extensive experiments on animals, 
states that fat necrosis is merely a special form of necrosis of fat tissue, 
differing from the simple necrosis chiefly in the sharp limitation of the 
affected area, usually by a wall of leukocytes and later by connective 
tissue, and the filling of the necrosed cells by the products of fat splitting. 

It seems to be due to the action of one of the ferments of the pan- 
creatic juice, most probably lipase (steapsin). As this ferment cannot 
be isolated, absolute proof is wanting. It may be that the lipase causes 
the fat splitting after some other ingredient of the pa'ncreatic secretion 
has injured the cell. 

The digestive enzyme is supposed to reach the fatty tissues of the 
abdomen by weakness of the pancreatic duct wall or pancreas capsule 
due to obstruction or inflammation. In such a condition bacteria may 
also escape and assist in the fat necrosis. Entrance of bile or intes- 
tinal contents into the pancreatic duct is said to favor the production 
Of fat necrosis. 

Lipase acting on the fat cells splits up their contained fat into 
glycerin and fatty acids. Glycerin diffuses, leaving behind the fatty 
acids. The cells become necrotic and eventually the fatty acids com- 
bine^ with calcium salts and are precipitated, while new growth of con- 
nective tissue encapsulates the area and diminishes its size. 

Dissemination of fat necrosis outside of the abdominal cavity has 
been observed as early as twleve hours after intraperitoneal injection 
in animals, the route of spreading being probably by the lymphatics. 



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A TEXT-BOOK OF PATHOLOGY 



Focal Necroses. — This is a condition of multiple small necroses in 
areas barely visible to the naked eye or discoverable microscopically. 
They occur in all parenchymatous organs and glands. The chief causes 
are vegetable toxins. In the small areas the nuclei first lose their stain- 
ing reactions, the cytoplasm later. There occurs an influx of leukocytes 
giving the appearance of an early abscess. These necroses are accounted 
for in two ways: bacteria or their products may be present directly in 
the foci, or the necroses may be due to obstruction of capillaries. The 
obstruction may be embolic or, as Pearce suggests, in the nature of a 
hyaline thrombosis due to hemolysis with collection of erythrocytic, 
debris. 

Hemolysis, or blood destruction, is a term limited to the red cells, 
and indicates destruction of the cell with dispersion of its hemoglobin. 
(The causes and other features are described under Pigmentation and 
Diseases of the Blood.) 

GANGRENE 

Definition. — Gangrene, formerly defined as the death of tissue 
en masse, is perhaps best defined as the putrefaction of areas of necrosis. 
It may be primary, when a particular bacterium produces a gangrenous 
inflammation as its direct result, as in malignant edema ; or secondary, 
when saprophytic bacteria decompose an area already necrosed from 
other causes. It may be dry or moist, according to the location and 
supply of fluids. It may, furthermore, be circumscribed, progressive, or 
metastatic. 

Primary gangrene constitutes a specific affection or, rather, a number 
of specific affections. Malignant edema, infectious emphysema, and 
some forms of anthrax may be included in this group. In these condi- 
tions there is violent infective inflammation, with practically immediate 
gangrene of the affected parts. 

Secondary gangrene is more common, and the appearances are very 
varied. The essential condition is putrefaction of a necrosed area. 

Dry gangrene is usually due to vascular disturbances. As a result 
of arterial obstruction it is seen in the extremities in senility, and it 
follows arterial embolism or thrombosis of whatsoever nature if the col- 
lateral circulation be insufficient to nourish the part. Freezing may pro- 
duce a dry form of gangrene, the vessels being blocked by thrombosis. 
Ergotism causes dry gangrene as a rule; the same may be said of Ray- 
naud's disease. Finally, dry gangrene may result from the moist form, 
when putrefaction is slow and evaporation of the fluids occurs. The 
putrefactive processes in the dry type are not marked and may cease 
entirely. Dry gangrene is generally circumscribed and the end-result of a 
typical case is mummification. The color is usually dark, finally black; 
early it may be yellow or brown ; rarely the tissues are very pale. There is 
little toxic absorption in these cases. 

Moist gangrene presents numerous varieties. It is rarely produced 
by arterial occlusion, but is the usual result of extensive venous occlusion. 
Internal emboli, as in the pulmonary arteries or veins or mesenteric 
arteries, not infrequently cause gangrene of this form. It also occurs 
in the lungs as a result of inspirational or other pneumonias, abscess, 



RETROGRESSIVE PROCESSES 



119 



neoplasms, bronchiectasis, and in diabetes. It is seen as a result of trau- 
matism and pressure in severe contusions (especially with vascular 
injuries), in intussusception and strangulation of the bowel; as a result 
of torsion in movable kidneys, spleens, or tumors. It is frequent in the 
obstructed or strangulated vermiform appendix. Extensive moist gan- 
grene of the extremities or other parts is not rare in connection with 
diabetes. The mucous membranes may become gangrenous as a result 
of various infections. A particular form is noma of the mouth and geni- 
talia. It is seen as a rare condition in certain skin diseases; and is not 
unusual in severe trophic lesions, as decubitus, cystitis, mal perforans, 
etc. 

In moist gangrene the consistency of the part becomes progressively 
softer. There may be local or widespread emphysema. The color 
is usually dark brown, due to disorganized blood-pigment; the skin 
commonly becomes black and is covered with blebs. About the area 
there may be a zone of coagulation necrosis with vascular thrombosis, 
or a zone of inflammatory reaction which will produce a line of demarca- 
tion. In some cases, especially the diabetic, neither of these zones is 
formed. 

The cells first succumb. The protoplasm and nuclei exhibit various 
evidences of degeneration, the nuclei disappearing and the cells becom- 
ing converted into granular detritus. Fat and the myelin-sheaths of 
nerve-fibers are reduced to free fat and fatty crystals. The muscle 
cells lose their striations and become fragmented; the axis-cylinders of 
nerves fibrillate. Hemorrhages into the area are common, due either 
to erosion of vessels and expulsion of their thrombi by the pressure of 
the blood-current, or to a genuine hemorrhagic condition the result of 
toxemia. Connective tissue and elastic fibers resist longer than the 
cells, but finally become liquefied. The affected area contains crystals 
of pigment, fatty acids, cholesterin, leucin, tyrosin, phosphates, and 
carbonates. Ammonia, the fatty acids, indol and skatol, sulphuretted 
hydrogen, carbonic acid and other gases, usually of pronounced odor, 
are formed. There is more or less toxic absorption from these areas. 

But two things can happen to an area of gangrene: it may progress 
and cause the death of the individual, or may become circumscribed. 
In dry gangrene and in the vascular forms of moist gangrene, limitation 
is the rule; the other moist forms tend to be progressive. In the cir- 
cumscribed form a line of demarcation is formed by inflammatory reac- 
tion, and the mass is finally cast off as a sphacelus or slough if the area be 
superficial, or encysted if the area be internal. The latter cases may be 
followed by reabsorption of the contents and calcification of the sac. 

POSTMORTEM ALTERATIONS 

Degenerative changes of the body as a whole after death are interest- 
ing chiefly in so far as they concern the circulation, the temperature, the 
musculature, and decomposition. The blood-vessels, especially the 
arteries, contract after death, and drive the blood into the capillaries and 
veins, where it is more or less free to sink to dependent parts through 
the influence of gravity, and in consequence the lower parts of the organs 
and of the body in general are congested. This is particularly marked 



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A TEXT-BOOK OF PATHOLOGY 



in the lungs, but occurs in practically all organs. The blood may remain 
entirely within the blood-vessels, but not rarely the coloring-matter 
diffuses itself through the tissues and causes pigmented areas (livores 
mortis) that may suggest antemortem bruises. 

The blood in the heart and other vessels tends to coagulate, though 
in some cases this is long delayed and remains imperfect. Usually dark 
red clots are found in the cavities of the heart and in the large vessels. 
Yellowish fibrinous clots are less likely to be postmortem in origin, but 
more often occur in cases in which death has taken a lingering form. 

If the temperature of a dead body be followed by frequent observa- 
tions there will be found a primary rise succeeded by a gradual and sus- 
tained fall until, in about one day, the temperature of the surrounding 
medium is attained. The primary rise is marked after a few diseases, 
like tetanus, and quite transient after cachectic diseases; in the latter 
case cooling proceeds much more rapidly. This elevation is due to the 
continuation of metabolism without radiation of heat by the blood pass- 
ing through the lungs. There may be local rises of temperature due to 
putrefaction. 

In so far as the musculature is concerned the most striking change is 
rigidity or rigor mortis, which is due to a coagulation of the muscle 
albumin or myosin, probably by reason of the lactic acid present. This 
occurs at different intervals, according to the cause and nature of death. 
Sometimes, as in deaths after electrical discharges, it occurs almost in- 
stantaneously; more commonly its beginning is delayed for some hours. 
It appears early in cases dying with active muscle metabolism, and late 
in wasting diseases. After twenty-four or forty-eight hours the rigidity 
disappears. Occasionally irregular postmortem contractions of the mus- 
cles take place, and distortions or even movements are thus produced. 

A day or so after death, in bodies not embalmed or kept covered with 
ice, and usually after rigor mortis has disappeared, putrefactive changes 
occur. As might be expected they begin where putrefactive organisms 
are most numerous, namely, in and near the intestines, but as it has been 
shown that bacteria migrate rapidly after death, degeneration of this sort 
may be general in a very brief time. The action of bacteria is undoubt- 
edly aided by the natural autolytic changes discussed before, processes 
which liberate bodies simpler than complex proteins and upon which 
bacteria can live. Discolorations, probably the result of sulphides act- 
ing upon hemoglobin, are seen in green patches over the abdomen and 
back. Gases often accumulate within the body cavities and later under 
the skin, loosening it or actually raising blisters. Putrefaction occurs 
early after death from infectious disease and gas poisoning and less 
rapidly after sudden or violent death. 



CHAPTER V 



INFLAMMATION AND REGENERATION 
INFLAMMATION 

Definition. — Inflammation is the local reaction caused by agents 
that have produced tissue injury. The essential element in this reaction 
is fluid and cellular exudation and the attraction to the place of injury 
of wandering cells. A less essential but almost invariable feature is 
local hyperemia, while the processes of repair or regeneration usually 
accompany, but are not strictly a part of, inflammation. By reason of 
the fact that the term "inflammation" was originally a clinical one and 
designated all the results of local injury, that is, damage, defensive 
processes, and repair, and further, by reason of the fact that injury and 
repair naturally go hand in hand in living tissues, it has always been a 
matter of difficulty for pathologists to determine what part of the pro- 
cesses occurring in an area of inflammation constitute its essence, and 
what part represents results or consequences. In the present state of 
knowledge we recognize and can distinctly separate two sets of phe- 
nomena following local injury, the first being reactive and defensive, 
the second, reparative. The latter, while intimately interwoven with the 
former, do not differ from regenerative processes that are known to 
occur without inflammation. Viewed in this fight the term "inflamma- 
tion" is restricted to the defensive processes that follow injury, while 
the repair of damage is a natural sequel manifesting the vital capacity 
of tissues to restore themselves. 

There are certain other consequences of inflammation that are some- 
times included among its essential phenomena. Thus, certain pathol- 
ogists insist that inflammation is general, not merely local; that the whole 
body participates in certain ways. There can be no doubt that the irri- 
tants causing inflammation as well as products of tissue destruction do 
gain access to the circulation to some extent, and thus occasion general 
results throughout the body, and it is also true that widespread co- 
operation may be induced through the action of the nervous system. 
These are results or sequels of inflammation, but not an essential part 
of the condition. When the local defensive mechanisms occurring in 
inflammation (let us assume, of bacterial origin) are inadequate, the 
micro-organisms may gain access to the general circulation and general 
"infection" result; when products of tissue destruction similarly 
escape into the general circulation an "intoxication" results. Neither 
of these is an essential part of inflammation, but rather the evidence 
that this process has been inadequate to fulfil its purposes. Such 
cooperation of the whole body as may be induced through the nervous 

121 



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A TEXT-BOOK OF PATHOLOGY 



system is reactive and is similar to that which must of necessity attend 
any local disease. It, too, is a consequence, but not an essential part, of 
inflammation. 

For purposes of description, however, it is better to include in the 
chapter on inflammation the regenerative processes that accompany 
it, and also some account of the general reactions of the whole body. 
Regeneration independent of inflammation, or with but slight evidences 
of preceding inflammation, will be separately considered later. 

Historical. — The earliest conception of inflammation was that of a specific entity. 
Subsequently various theories were offered in explanation of the several phenomena 
or symptoms. First, the blood-vessels were supposed to be influenced through 
the nervous system (vascular theories). Next, it was taught that the inflammatory 
irritant excites proliferative changes in the tissues (thus giving rise to round cells), 
and that this stimulation of the cellular activity invites more blood to the part (hence 
the hyperemia). This was the cellular and attraction theory of Virchow. Others, 
notably Cohnheim, described the emigration of leukocytes from the blood-vessels, 
and held this to be the essential feature of inflammation. This emigration was 
first described by Dutrochet (1824), Waller (1842), and Strieker; but Cohnheim 
was the first to systematize the emigration theory. According to Virchow, the first 
step is a formative stimulation of the cells; according to Cohnheim, degeneration of 
the vessels leading to emigration; according to Weigert, at least in many cases, the 
first step is necrosis of the parenchymatous cells. Metchnikoff and his students 
would elevate phagocytosis to the position of the essential feature of inflammation, 
but the prevailing opinion is that reactive tissue changes and enzyme activity are 
equally important, both within and without the cell. 

Galen and his followers defined inflammation by giving the cardinal 
symptoms: heat (color), redness (rubor), pain (dolor), and swelling 
(tumor). To these may be added altered function (functio Icesa). 

Phenomena of Inflammation in Vascular Tissues. — These may 
be well studied in the mesentery or tongue of a frog. When the mesen- 
tery is exposed and spread under a microscope and a localized area in 
jured, the first visible effect is a very temporary contraction of the 
arteries, which may disappear before the examination can be made. 
It is followed by dilatation of the arteries, and then of the capillaries 
and veins. The tissue becomes distinctly more vascular than normal 
as capillaries in which there had been only plasma or a few corpuscles 
become distended with blood, and, therefore, more distinct. The blood- 
current is at first more rapid than normal, then slower, and may finally 
stop entirely (stasis), especially in the capillaries and veins in the center 
of the inflamed area. Notable changes are seen in the circulating cor- 
puscles. It will be recalled that under normal conditions the corpuscles 
circulate in the middle of the vascular stream, leaving a clear plas- 
matic zone adjacent to the vessel wall; in this zone may be seen leuko- 
cytes traveling somewhat more slowly than the central corpuscular 
stream. As the current becomes slower the leukocytes in the plasmatic 
zone increase in number and stick to the vessel walls, at first here and 
there, holding on uncertainly, but finally becoming more firmly attached 
and arranging themselves in a continuous row. In the capillaries clumps 
of leukocytes frequently alternate with masses of red corpuscles, or of 
red and white corpuscles in their customary proportion. Next, it may 
be observed that the leukocytes are passing through the walls of the 
capillaries and veins and spreading in the outside tissues. At first a bud- 



INFLAMMATION AND REGENERATION 



123 



like projection pushes itself through the vessel wall, then more and more 
follows until the whole leukocyte has escaped into the tissue space 
outside the vessel. At the same time a certain number of red cor- 
puscles pass through the capillary walls, and altered plasma escapes and in- 
filtrates the tissues, carrying with it fibrinoplastic substances which partly 
by themselves and partly by the action of other elements in the exudate 
cause the appearance of fibrin in the form of a delicate coagulum. Some 
of the leukocytes enter the lymph-channels and thus return to the circula- 
tion; others suffer degeneration and destruction locally. If the exposure 
of the frogs' organ cease at this time, the circulation will soon resume its 
proper rate, the leukocytes will supply enough ferment to dissolve the 
fibrin and will remove any debris that may have collected, while the blood 
stream will reabsorb fluid and probably take up exudated red cells. 

However, should the exposure be prolonged, the irritation excessive or 
bacteria be added, the exudative process becomes more intense, degene- 
ration greater by the microbic or leucocytic enzymes or the lack of fresh 
blood, and pronounced reaction of the tissues locally against the injury 
is noted. In the perivascular tissue the emigrated leukocytes are found in 
tissue spaces and tend to accumulate where the injury is greatest. If 
there be a large area of destruction, these cells surround it. The 
leukocytes exhibit their phagocytic power by enclosing bacteria, fragments 
of dead cells, and debris. The enclosed parts are dissolved by the 
intracellular ferments and are soon unrecognizable. Some of the 
phagocytes are themselves destroyed in this attempt to remove invading 
bacteria and degenerated cells; and becoming, in turn, degenerated, break 
down into a debris upon which other phagocytes feed. There appear 
within the cellular exudate also large mononuclear phagocytic cells with 
large palely staining nuclei, the so-called macrophages. These take up 
all kinds of debris or even whole leukocytes and red blood-cells. Their 
origin and functions will be considered later. 

While this is going on, reparative processes appear in the shape of 
round newly formed connective-tissue cells which alter their form to 
spindle or irregular contour, and finally produce fibrillar projections. 
These are fibroblasts, the principal regenerative cells. 

In structures in which there are parenchymatous (archiblastic) 
cells the latter undergo various degenerative changes, such as cloudy 
swelling, edema, mucous degeneration, fatty degeneration, or even 
necrosis. Less frequently proliferation of the parenchymatous cells 
takes place. 

Every case of inflammation does not present all these phenomena, nor 
is the subsequent fate of the exudate and altered cells always the same. 

Phenomena of Inflammation in Avascular Tissues. — Some of 
the processes of inflammation have been best elucidated by experi- 
mental inflammation of the cornea. It will be recalled that this struc- 
ture is composed of layers of parallel lamellae, the direction of the strands 
in one layer being at angles to that of the fibers of adjacent layers. 
Anastomosing lymph-channels occupy the spaces between the fibers 
and layers, but there are no blood-vessels. A very slight injury of the 
cornea may be followed by no other result than slight swelling of the 
corneal corpuscles around the point of the injury and subsequently multi- 



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A TEXT-BOOK OF PATHOLOGY 



plication of these cells to repair the damage. This slight change cannot 
be readily demonstrated. Usually there is seen around the injured spot 
a hazy zone which is composed of masses of leukocytes that have been 
attracted to the center of irritation. These escape from the hyperemic 
conjunctival vessels at the periphery of the cornea. The alteration 
(dilatation, degeneration of the walls) of these vessels may be due in 
part to reflex nervous influences, and in part to the direct action of toxic 
substances generated at the site of the primary corneal injury and 
diffused to the surrounding tissues. 

The corneal corpuscles themselves swell, undergo nuclear division, 
and to some extent perhaps become free (phagocytic) cells. In more 
intense grades of inflammation the local degeneration of the corneal 
corpuscles causes a visible defect (erosion, ulcer), and the surround- 
ing zone of leukocytic invasion is pronounced. In cases of marked 
corneal inflammation new blood-vessels are later formed at the sides 
of the cornea, and pushed into its previously avascular structure; the 
subsequent phenomena are practically the same as those found in in- 
flammation of vascular tissues. 

In the case of inflammation of the heart-valves no migration of 
leukocytes to the diseased focus occurs in the early stages. The endo- 
thelial cells at the point of injury (near the free edge of the valve) swell 
and present nuclear division and also more or less degenerative change; 
the tissues at the base of the leaflets become hyperemic and some 
emigration of leukocytes occurs in this situation. To this may be added 
something from the blood stream in the shape of coagula made up of 
fibrin and circulating cells. Thus, as in the case of the cornea, cellular 
destruction and proliferation occur at one place (the point of injury), 
while the vascular phenomena and emigration of leukocytes are found 
at some distance. In both cases there may eventually be an ingrowth 
of loops of capillary blood-vessels from the vascular periphery 
into the avascular structure, and then local emigration of leukocytes 
from the capillaries may take place. 

The phenomena of inflammation in particular must now be 
separately considered. 

1. Changes in the Vessels. — The first effect of irritation may be 
momentary contraction of the arteries; but this is rarely observed. 
Usually the arteries dilate at once, and dilatation of the capillaries 
and veins promptly follows. This is at first a regular or uniform dis- 
tention, but shortly becomes irregular, causing inequality of caliber and 
tortuosity. The cause of this dilatation was formerly located in the 
nervous system, and undoubtedly nervous influences do play a part 
in some cases at least, but the more important cause is probably some 
degeneration of the vessel walls. The primary dilatation may be due 
to the direct effects of the toxic agent causing the inflammation or to 
products of cell degeneration it has occasioned. It may be purely func- 
tional at first, but later is surely degenerative. The microscope does 
not reveal this, but some of the phenomena connected with exudation 
and the circulation of the blood show that there is some lesion of the 
vessel walls. There are certain visible changes in the vessels, such as 
swelling of the endothelial cells and increase of the intercellular sub- 



INFLAMMATION AND REGENERATION 



125 



stance, and some undoubted though invisible changes, such as increased 
stickiness of the endothelial cells. The last-mentioned condition 
and the swelling of the endothelial cells which thus encroach upon the 
lumen of the vessels are conditions that, together with the dilatation of 
the blood-vessels, occasion slowing of the blood-current and adhesion of 
the leukocytes to the vessel wall. 

In the later stages of inflammation karyokinetic changes and con- 
sequent multiplication of the endothelial cells of the capillaries are ob- 
served. The new-formed endothelial cells are utilized in the production 
of new blood-vessels. (See Granulation Tissue.) 

Influence of the Nervous System. — It is likely that the nervous system 
through its vasomotor mechanism plays an important role both centrally 
and peripherally in the vascular and exudative phenomena of inflam- 
mation. Dilatation of the vessels may be favored by weakness of the 
constrictors or stimulation of the dilators. This is illustrated by the 
severe inflammations resulting from trivial causes in paralytic parts, and 
by the occurrence of sympathetic inflammation in one eye following 
disease of the other. In the 
latter instance the trophic 
nerves are also concerned. 

2. Exudation. — As the blood- 
current grows slower the leuko- 
c} r tes in the plasmatic zone of 
the blood-stream increase in 
number and cling to the wall of 
the vessel. This is partly a 
mechanical result of the slower 
rate of the blood-current, and 
. partly the result of the adhesive- 
ness of the vessel walls and pro- 
jection of the endothelial cells; 
to this may be added the fact 
that the blood within the vessels 
of an inflamed area is richer in 
corpuscles than normal because serum oozes out early. All the fore- 
going factors have a hand in destroying the layering of the blood 
current by which the normal parietal zone is poor in cells, the mesial 
current rich in cells. Possibly the attractive (chemotactic) influence 
of the agents causing the inflammation may play some part by drawing 
the leukocytes to the walls of the vessels (see below). Finally, the leu- 
kocytes pass through the vessel walls between the endothelial cells and 
collect on the outside of the blood-vessel, whence they more slowly 
migrate through the tissue (Fig. 28) . At first a bud-like proj ection pushes 
itself through the wall between the endothelial cells, then more and 
more of the corpuscle follows until the whole cell has escaped. When 
outside of the blood-vessel, the cell creeps through the tissue in the inter- 
cellular spaces, often elongating itself in narrow places to a linear 
form, and again swelling to its normal rounded form where fluid exudate 
has widened the spaces. This emigration of leukocytes occurs to a slight 
extent normally, but is abnormal in degree in inflammation. Cohn- 




Fig. 28. — Inflammation of the mesentery, 
showing overfilling of the blood-vessels, with 
emigration of leukocytes and diapedesis of red 
corpuscles (Ziegler). 



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A TEXT-BOOK OF PATHOLOGY 



heim ascribed it to disease of the vessels — increased permeability — the 
leukocytes being purely passive. Later observation indicates that the 
chief role in this excessive emigration must be assigned to the stimulated 
ameboid movements of the leukocytes. Degeneration of the vessel 
walls, especially swelling and softening of the cement substance between 
the endothelial cells, and the pressure of the blood, aid, but only to a 
minor extent. The cause of this active ameboid motion and tendency to 
emigration has recently been found to be an attractive force peculiar to 
the causes of inflammation. Stahl, and later Pfeffer, found that certain 
substances exert an attractive or repellent force upon low forms of 
vegetable and animal life, upon spores of plants, and upon bacteria. 
To this force the name chemotaxis has been given, and the terms positive 
and negative chemotaxis are used to designate the attraction and the 
repulsion respectively. The irritant substances which directly cause 
inflammation are positively chemotactic in action; and in cases in which 
mechanical injury causes inflammation, ' the cells primarily destroyed 
supply material which acts with positive chemotactic power; perhaps 
certain chemical or mechanical irritants may exert this influence 
to a minor degree but cellular debris has a definite power in this direction. 
There is, however, after mechanical irritation no such prompt or pro- 
nounced leucocytic response as after the entrance of micro-organisms ; 
there are a few minor exceptions to this which will be mentioned at a 
later time. The cells that respond to this influence are in nearly all 
cases at first polynuclears for mononuclears are not so prompt in obeying 
the call. What determines this is not clear but it will be seen later that 
the removal of debris and digestion of more organized matter is left to 
the wandering cells. Other forms to respond early are eosinophiles 
and sometimes these are very abundant in acute inflammation. 

In somewhat later stages mononuclears also emigrate, and as the 
polynuclear forms disappear the mononuclear becomes more and more 
predominant. In part these doubtless emigrate from the blood-vessels, 
but the greater number is derived from the lymph-channels and regional 
lymphoid collections, for such cell groups are exceedingly widespread 
throughout various tissues and organs. The lymphocytes are prone 
to occur in groups, which has led some authorities to attribute their 
presence to hyperplasia of existing lymphoid collections, and to some 
extent to the attraction exerted on the lymphoid cells of the neighboring 
lymph-spaces toward the existing lymph-nodes in the affected area. 
While the tendency is to group together, they also increase among the 
growing fibroblasts, and, as said above, crowd out the polymorphonu- 
clears. Plasma-cells and mast-cells are also found, but as the 
significance of these is still unclear, separate reference will be made 
to them later. The plasma-cell undoubtedly plays an important role 
in some cases, as the inflammatory exudate may consist almost wholly 
of this type of cell. 

The microscopical appearance of the tissues after emigration of 
the leukocytes is characteristic. The capillaries are dilated and ob- 
scured by a mantle of exuded white corpuscles, and the tissue around 
swollen by the fluid and infiltrated with migratory leukocytes. The sub- 
sequent distribution and appearance of the leukocyte depends very 



INFLAMMATION AND REGENERATION 



127 



much upon the character of the inflammation and of the tissues in which 
it occurs. 

The local cellular changes going on consist of fatty, cloudy, albu- 
minoid, or dropsical degeneration of organ cells, while hyaline or mucoid 
metamorphosis is seen in connective-tissue cells. 

The cellular character of the exudate varies somewhat with the tissue 
involved and the nature of the irritant. For example, in the pyogenic 
infections at the height of the condition one sees almost exclusively 
polynuclears. In tuberculous inflammations lymphocytes predominate; 
while in pneumonia, polynuclears and epithelial cells are in greatest 
numbers. (Refer to Types of Inflammation.) 

Diapedesis of Red Corpuscles. — Finally, a certain number of red 
corpuscles escapes from the capillaries by diapedesis. This is a purely 
passive process so far as the red corpuscles are concerned, being due to 
pressure of the blood. It is particularly marked when stasis and con- 
sequent intravascular thrombosis has occurred. In very intense in- 
flammation accidental hemorrhage per rhexin may add to the blood in 
an exudate. 

Role and Fate of the Leukocytes. — The most essential element in the 
defense against the injurious agents that cause inflammation is the emi- 
grated polymorphonuclear leukocyte. This cell possesses a marked 
capacity to swallow or ingest bacteria or other foreign bodies, which 
has given the process the name phagocytosis, and the cell exercising this 
function the name phagocyte. When bacteria (especially pyogenic 
micrococci) or small particles of insoluble material, such as carmin or 
carbon, are introduced into the tissues or into serous cavities, polymor- 
phonuclear leukocytes speedily gather about and incorporate the foreign 
bodies in their protoplasm. So far as bacteria are concerned, some 
preliminary action is exerted on them by the blood-serum of the fluid 
exudate (see below). This is demonstrated by the fact that the poly- 
morphonuclear cells will take up larger numbers of micrococci from a 
suspension in serum than from one in normal salt solution. The sub- 
stances which act to prepare the micro-organisms are termed opsonins 
(see p. 271). It has lately been stated upon very fair grounds, that agglu- 
tination of bacteria is one of the first steps taken by the body in its 
defense and that this process enables the phagocytes to act upon the 
thus immobilized microbes. After their ingestion the micro-organisms are 
either digested within the phagocytic leukocyte and thus disappear, or the 
phagocyte with its contents enters lymphatic channels and reaches the 
regional lymphatic nodes. Thus the micro-organisms are disposed of and 
removed from the center of infection as speedily as possible. Insoluble 
foreign bodies and products of tissue destruction (fatty globules and 
detritus) are also taken up by the phagocytic leukocytes and dissolved 
or removed to the neighboring lymphatic nodes. In this combat with 
the foreign invaders a certain number of the leukocytes perish and may 
be found in various stages of disintegration. Some of them are ingested 
by other polymorphonuclear leukocytes, but in the later stages of inflam- 
mation they are found enclosed in other phagocytic cells of large mono- 
nuclear type, which will be described presently. 

The various processes described bring about a removal of the micro- 



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A TEXT-BOOK OF PATHOLOGY 



organisms or other causes of inflammation, and at the same time a steady 
diminution of the number of polymorphonuclear leukocytes at the 
point of inflammation. The lymphocytes now begin to be more con- 
spicuous in number. Their role, however, is less definitely determined. 
Some of them seem to undergo a swelling and transformation into the 
large mononuclear phagocytic cells that will be described below. It 
was formerly held that some of them become engaged in the process of 
reproduction of tissue, being first converted into formative or fibroblastic 
cells. This view is probably erroneous, the evidence being that neither 
the ordinary lymphocyte nor the variety known as plasma-cell has such 
a function. 

The eosinophile leukocytes may sometimes be abundant in inflam- 
matory exudates, and it has been suggested that they are active in 
throwing out bacteriolytic substances. Further proof of this assump- 
tion must be forthcoming. 

In all of these processes in which the emigrating leukocytes are 
concerned soluble substances and enzymes are essential. These will be 
referred to after the liquid exudation has been discussed. 

Large mononuclear phagocytic cells become conspicuous in the area 
of inflammation after the primary leukocytic phase begins to subside, 
and in certain inflammations they are so almost from the beginning. 
These cells are of variable size, always large, and sometimes of giant 
proportions. The rather large pale nucleus and the phagocytic prop- 
erty of the cells are their distinguishing characteristics. The general 
term "macrophages" may be used to designate them, though it indi- 
cates no special derivation. The origin, indeed, is still uncertain, but 
among the possible sources of derivation are the lymphocytes, the 
endothelium of lymph-glands and channels, blood-vessel endothelium, 
and various wandering tissue-cells, which belong either to the lymphatic 
or to the myeloid series. It has been asserted that there are several 
types of cells concerned, that is cells of entirely separate derivations, 
such as endothelium and myelocytes. From other sources there comes 
the statement that all wandering cells have one embryonic progenitor. 
This is not the place to enter upon the academic question of histological 
derivation but we feel that from the stand-point of finished cells or those 
normally differentiated, the endothelium and the wandering tissue-cells 
both have a part in the phagocytosis seen in late inflammation. The 
wandering cells do not differ in appearance from the so-called lymphocyte 
small or large, the latter as seen in f ollicular centers, except in the case of 
plasma and mast cells. The small mononuclears from the blood or local 
collections, swell into the form usually called large mononuclear and then 
resemble the endothelial cells; mitoses are common. To this group of 
cells Maximow has given the name polyblasts. These cells do not 
originate from the local connective tissue cells nor do they produce 
this tissue later. The clasmatocytes of Ranvier are granular polyhedral 
cells with a dense nucleus ; they are in all probability connective tissue 
cells with swollen cytoplasm but in which the nucleus has not grown 
large and loose as is the custom. The macrophages are specially con- 
cerned in taking up leukocytes and fragments of cellular destruction. 
Sometimes a number of polymorphonuclear phagocytes, with their own 



INFLAMMATION AND REGENERATION 



129 



inclusions, all more or less degenerated, are found within a macrophage, 
and there may be, in addition, red corpuscles and debris of other cells. 
The complete digestion of these contents may occur in part in the area 
of inflammation, but some of the macrophages, like some of the polymor- 
phonuclear phagocytes, perhaps find their way to regional lymphatic 
nodes; and similar cells primarily make their appearance in the lymphatic 
nodes when the polymorphonuclear phagocytes invade these structures. 

Plasma-cells. — The cell described under this term by Unna is a small 
cell whose protoplasm stains a violet blue with methylene-blue. There 
are no distinct granules, though sometimes the protoplasm is slightly 
granuloid. This cell is one of the so-called lymphocyte series. The 
nucleus is usually eccentrically placed, with denser chromatin around the 
margin, and surrounded by a clear or palely stained zone in the protoplasm. 
The cell varies in size from that of the small lymphocyte to that of the 
large mononuclear leukocyte. Karyokinesis has been observed in a few 
cases. The plasma-cell is probably an altered lymphocyte which has 
escaped from the blood-vessels. Some hold that it is a form of connective 
tissue cell and that it is concerned in regeneration of connective tissue. 
This is unproved and unlikely. The plasma-cell is found in inflam- 
matory exudates of all sorts and in the lesions of the specific infectious 
diseases — tuberculosis, leprosy, syphilis, etc. 

The plasma-cell of Waldeyer is different from that above described. It is identical 
with the mast-cell of Ehrlich. This is a cell containing large basophilic granules. 
(See Diseases of the Blood.) It occurs in inflammatory processes of a chronic charac- 
ter and in various tumors and degenerative lesions. 

Giant-cells, containing multiple nuclei, are found occasionally in the 
late stages of acute inflammation but. since they seem more characteristic 
of chronic inflammation their description will be reserved until that is 
discussed.. 

Exudation of Liquids. — Coincidentally with leukocytic emigration 
there is exudation of more or less altered blood-plasma. The amount of 
liquid and the character of the exudation vary with the nature and condi- 
tion of the tissue affected and the character of the irritant. In loose cellu- 
lar tissues and in inflammation of membranes lining cavities large 
quantities of liquid are poured out of the vessels, while the reverse is 
seen in denser parts. 

The exudate is richer in albumin and more coagulable than dropsical 
fluid, which is a further indication that the blood-vessels are more per- 
meable in inflammation than in health or mere congestion. It is prob- 
able, moreover, that the capillary walls act in a secretory manner, as 
do the walls of the lymphatic channels. This would in some measure 
explain the difference between inflammatory exudate and dropsical 
liquids. The accumulation of exudate in the tissue may be so abundant 
that the term inflammatory edema is justified. In such cases, as in all 
inflammations to a less extent, the cause of the retention of liquid in the 
inflammatory area is in part a reduction of tissue tone or elasticity which 
prevents the movement of the fluid toward the efferent lymph-channels. 
Thrombosis of lymphatic vessels, induraton of surrounding tissues, 
and edematous and cellular swelling of regional lymph-nodes are also 
causes for the retention of liquid exudate in an inflamed area. 

9 



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A TEXT-BOOK OF PATHOLOGY 



After its exudation the fluid may undergo coagulation by interaction 
with fibrin ferment derived from disintegrated leukocytes with forma- 
tion of fibrin and consequent solidification of the inflamed area. When 
inflammations affect mucous membranes there is usually active stimu- 
lation of the epithelial cells and outpouring of mucus, which materially 
alters the exudate. 

The exudate plays an important role in inflammation. Among its 
uses may be mentioned that it serves as a diluent of noxious bodies, 
that it brings from the blood substances which aid in destroying the irri- 
tants, and that it may carry similar substances derived from the leuko- 
cytes, either secretions or products of their degeneration. Occasionally 
it has the unfavorable action of carrying away and thus spreading 
throughout the system the causes (bacteria, for example) or products 
of the inflammation. In the case of fibrinous inflammation, the fibrin 
serves to strengthen the limiting wall by which an inflamed area is sur- 
rounded. The highly nutritious character of the liquid is doubtless of 
importance in the proliferative processes that are presently to be 
described. 

3. Chemical Processes Involved in Inflammation. — Many of the 
features of inflammation have been made clearer by recent studies of 
certain chemical relations of the cellular and fluid exudates. It has been 
found that the leukocytes carry in their substance an active proteolytic 
enzyme which acts best in an alkaline medium. This enzyme doubtless 
operates to dissolve bacteria and other albuminous bodies ingested by the 
phagocytic leukocyte. When this enzyme is liberated by disintegration 
of emigrated leukocytes it is capable of attacking the tissues and soften- 
ing or digesting them, but this result is prevented when sufficient fluid 
exudate is present, because the latter contains an anti-enzyme which 
destroys or in some manner neutralizes it. This is, perhaps, the same 
anti-enzyme which is present in normal blood-serum, and which is cap- 
able of restraining the action of trypsin. Should leukocytic exudation 
become excessively abundant, owing, for example, to highly chemotactic 
micro-organisms, or should the physical nature of the tissues prevent an 
adequate fluid exudate, both factors favoring cell necrosis, the amount of 
leukocytic enzyme liberated becomes disproportionate to the amount of 
anti-enzyme, and there results a proteolytic softening of the tissues and 
exudate with resulting pus formation. This disproportion of enzyme and 
anti-enzyme, with factors that cut off blood supply and help to activate 
intracellular enzymes (autolysis), determines the occurrence of suppura- 
tive instead of non-suppurative inflammation. It is probable that very 
few if any micro-organisms have the power to elaborate sufficient enzymes 
to produce pus without all the above factors. 

In the later stages of inflammation, when the leukocytes have largely 
disappeared and the mononuclear phagocytes are in evidence, a differ- 
ent proteolytic enzyme is found. This has been studied especially in 
tuberculous tissues with abundant epithelioid cells. This enzyme acts 
best in an acid medium, and is probably active in the destruction of 
leukocytes and various cellular remnants ingested by the macrophages, 
from which it is derived. Opie has suggested the names leukoprotease 



INFLAMMATION AND REGENERATION 



131 



and lymphoprotease for the enzymes derived from the leukocytes and 
mononuclear cells respectively. 

Other chemical processes besides those mentioned are involved in 
inflammation. The first effect of the action of inflammatory irritants, 
whether merely mechanical or micro-organismal, is cellular destruction, 
and consequent liberation of substances that are chemotactic and to 
some extent toxic. There follows the exudation of leukocytes and liquid. 
Chemical combination between fibrin ferment derived from disintegration 
of leukocytes or other cells and the liquid exudate causes fibrin for- 
mation, and thus some solidification of the inflammatory exudate. 
Later, this fibrin, together with the more or less degenerated cells in 
the area of inflammation, may be digested by the action of the leuko- 
protease before described, and perhaps by the action of similar if not 
identical enzymes derived from the blood-serum. 

Micro-organisms call forth special chemical defenses. As has been 
related, the micro-organisms are in large part ingested by phagocytic 
leukocytes and are in some way destroyed within these, assisted by the 
agglutinins and opsonins. The small quantity of bactericidal substance in 
the blood may be increased in response to local or general infection. 
Phagocytosis, either by leucocytes or mononuclears, may occur with living 
organisms but some form of preparation, as suggested above, certainly 
favors it and it is well known that chemotaxis plays a distinct role in the 
process. Therefore highly virulent bacteria, which are known to have 
a more repellent than attractive influence upon leucocytes, are not so 
readily caught by these cells. After ingestion the microbes are subjected 
to the emzymes of the cells and are dissolved, although in some cases the 
phagocyte may have swallowed a bacterium with great resistance, or too 
many of them, and may itself perish. Its duty accomplished, the cell 
may remain quiescent in the vicinity or move to some gland to lay down 
its debris, or it may return to the circulation. Some of the micro-organisms, 
doubtless, are destroyed and the remnants carried off into the lymphatic 
channels without the aid of phagocytes. It is asserted by some observers 
that besides the enzymes of blood- and tissue-cells described above, there 
is in these cells a separate and extractable substance (endolysin) which can 
destroy bacteria. Its office in inflammation is not understood. 

4. Proliferative Changes. — The stage which succeeds the alteration 
from polynuclear to mononuclear, in favorably progressing instances, is 
one in which the later type dominates the field and for the most part the 
type which exceeds all others is the small mononuclear cell. This cell, 
already mentioned, comes chiefly from the blood stream or from the so- 
called adventitial cells, doubtless lymphocytes also, or from local or nearby 
regional lymphoid collectioDs. There are however, added to these, swollen 
and rounded connective tissue cells. The picture so produced has been 
called u round-cell infiltration. " There are, however, numerous forms like 
large mononuclears, endothelial cells, plasma and mast cells also present. 

Accompanying this infiltration, the connective tissue of the part 
becomes active in the direction of repair. The cells not destroyed in the 
inflamed area or those on its border undergo hyperplasia and, carrying 
on their natural function, elongate to produce connective tissue fibrils. 



132 



A TEXT-BOOK OF PATHOLOGY 



These cells, fibroblasts, are larger than their predecessors, are usually 
somewhat granular and have a large clear nucleus. 

Granulation Tissue. — -When the proliferative changes are active, 
new blood-vessels, formed by multiplication and lateral outgrowth of 
the endothelium of the pre-existing vessels, are a conspicuous feature. 
These, surrounded by the various forms of round cells above described, 
and sometimes giant-cells, constitute granulation tissue (See also Repair 

of Wounds and Regeneration). Such 
granulation tissue is especially con- 
spicuous on the floor of ulcers, and 
exemplifies the regenerative processes 
which follow immediately in the wake 
of the frank inflammatory reaction. 

A very striking cell seen in chronic 
inflammation and in the reparative proc- 
esses here discussed is the foreign 
body giant cell 1 with numerous peri- 
pherally located nuclei and a homo- 
genous center. 

Their origin may be in rapid mitosis 
of the nucleus, too rapid for the pro- 
toplasm to divide synchronously, or 




s \ 




, . > l#f* 



Fig. 



29. — Acute appendicitis, with 




extensive round-cell infiltration of all 
of the coats of the appendix. 



Fig. 30. — New blood-vessels and fibroblastic 
cells in a beginning adhesion of the pericardial 
layers. 



more probably a coalescence of leukocytes or mononuclears in close 
apposition. The latter method has been explained further by reasoning 
that, when a number of cells are bent upon phagocyting a certain object, 
they expose to it a part of their cell wall prepared for its reception and 

1 Other kinds of giant-cells are: Myeloplaxes are giant-cells with uniformly dis- 
tributed nuclei and a homogeneous protoplasm, such as are seen in the bone-marrow 
and tumors. Parenchymatous giant-cells are found in tumors, in regenerating 
interstitial tissues, or in the parenchyma of organs. The nuclei may be irregularly 
distributed, but are commonly connected by narrow isthmuses of chromatin. They 
arise by rapid nuclear division. 



INFLAMMATION AND REGENERATION 



133 



that the surface tension and enzymic concentration at this point being 
the same, the several protoplasms flow together. This might be aided 
by the surrounding tissue pressure. The distribution of the nuclei 
around one side of the wall, is thought to be due to the fact that they 
are inactive in phaocytosis, the protoplasm moving en masse to approach 
the object of attack. These giant cells are to be found in special forms of 
inflammation but are particularly prominent in the removal of foreign 
bodies. 

There has been a long discussion as to the proper interpretation of 
inflammation and repair. By some writers the former ends at once when 
the latter appears while by others, fibroblastic reparative processes are 
included under the conception of inflammation. Since reparative fibro- 
blastic changes are the result of tissue irritation, the question seems 
academic. The stimuli probably reside in the products of cellular 
cleavage for it has been observed that if protein or its hydrolytic deriva- 
tives be injected into an animal proliferation takes place. It would seem 
therefore that so long as substances remain which excite infiltration, 
karyokinesis and fibrous tissue growth, inflammation may be assumed to 
continue. 

5. Degenerative Changes in the Tissues. — The first attack of in- 
flammatory irritants is made upon cells of fixed tissues, that is, upon 
cells of the parenychma of an organ, upon the connective-tissue cells, 
or upon the walls of blood-vessels. The emigration of leukocytes and 
their combat with the irritants follow. In the case of bacteria which 
contain within their substance positively chemotactic bodies, it would 
seem probable that there is an immediate activity of these bodies; but 
various considerations make it more probable that even in the case of 
bacteria the first effect is exercised upon fixed cells. In the case of 
mechanical irritants damage or complete destruction of cells is the 
first step toward inflammation. The demonstration that tissue degenera- 
tions liberate positively chemotactic substances explains how the pheno- 
mena of inflammation are brought about. The degenerative changes 
may be merely physiological (some form of altered functional activity), 
or there may be structural alterations, such as cloudy swelling, mucoid 
degeneration, liquefaction, fatty change, coagulation, or other forms of 
necrosis. The nature of the degeneration depends largely upon the sev- 
erity of the irritation. Very powerful irritants cause necrosis at once, and 
not inflammation. It is the irritants which disorder, but do not entirely 
destroy, cells that are especially apt to excite inflammation. The cellular 
degenerations now under discussion are entirely different in significance 
from the more conspicuous secondary cellular degenerations considered 
below. The primary degenerations occasioned by the first attack of the 
irritant are often inconspicuous and inferential rather than demonstrable. 

Secondary Cellular Degenerations. — 'When inflammations attack 
tissues containing epithelia or other parencyhmatous cells the latter 
suffer secondary degenerative changes, cloudy swelling, fatty or mucoid 
degeneration, and total necrosis. These secondary cellular changes may 
serve to spread and intensify the original inflammation, and are, moreover, 
especially harmful to the functional activity of the diseased organ or 
tissue. The cause of these degenerations may be the same toxic agent 



134 



A TEXT-BOOK OF PATHOLOGY 



which initiated the whole process or, on the other hand, the pressure of 
exudates and the circulatory disturbances incident to the inflammation. 

Etiology. — Irritation by mechanical, chemical, thermal, or infec- 
tious agents causes inflammation when it is severe enough to dis- 
turb the vitality of the tissue and not sufficient to cause extensive 
necrosis at once. When the irritant is brought to bear upon the tissues 
directly, there is probably, first, cell degeneration, followed by vas- 
cular disturbances and emigration. Micro-organisms may act by first 
destroying the cells, or may liberate from their substance some poison 
(protein) which is irritant and chemotactic. Disturbances of circu- 
lation, innervation, or metabolism may so alter cellular processes as to 
occasion the liberation of irritating and chemotactic products. 

In the experience of surgeons bacteria stands out conspicuously as 
the almost invariable cause of "inflammation." This term, however, 
is used in a clinical rather than a true pathological sense. The proc- 
esses concerned in the healing of uninfected wounds and in other 
cases of injury unaccompanied by infection are just as truly inflam- 
matory. . It must be recognized that non-bacterial injuries to tissues 
liberate substances by cell destruction which are capable of producing 
the phenomena of inflammation. Among the causes of inflammation 
in this pathological sense must be included certain endogenous proc- 
esses, notably of circulation, innervation, and metabolism, which cause 
local cellular degeneration, followed by exudative and reparative 
phenomena. 

Special Forms of Inflammation. — Various classifications may 
be used in describing forms or types of inflammation. The most 
natural is that which follows the anatomical changes, Thus we may 
distinguish (1) exudative inflammation, or the form in which the fluid 
and cellular exudation from the blood-vessels is the predominating 
element in the pathological process; (2) parenchymatous or degenerative 
inflammation, or the form in which destruction of the parenchyma cells 
is the leading feature; and (3) productive inflammation, in which prolif- 
eration is the striking characteristic. The nature of the cause, as well 
as the resistance of the body or of the affected part, determine the par- 
ticular form in a given case. 

A number of subvarieties may be described, but it must always 
be remembered that inflammation is essentially the same in all cases. 
The three processes — exudation, degeneration, and proliferation — are 
present in greater or less degree in all forms, although in some cases one 
features, in other cases another, may be most conspicuous. 

Types of Inflammation. — 1. Edematous or serous inflamma- 
tion is characterized by a copious exudation of fluid with compara- 
tively little cellular matter, as in edema of the larynx, serous effusions 
in the serous sacs, etc. The local forms of edematous or serous inflam- 
mation are usually expressions of intensely irritant causes; the serous 
inflammations of serous cavities, however, are not necessarily of this 
severe grade. Indeed, in many cases serous inflammation may be a mild, 
subacute or chronic, process, which may subside gradually, leaving the 
serous membranes slightly thickened or adherent. This adhesion is 
due to the fact that fibrin collects upon the serous surface during the 



INFLAMMATION AND REGENERATION 



135 



acute stage, the fluid remaining free in the sac. The fluid is removed 
by absorption; the fibrin, by digestion. Lasting adhesions remain when 
proliferative changes are firmly established before the digestive processes 
can complete their work of removing the fibrin deposits. The fluid in 
inflammatory exudations differs from dropsical fluid in containing more 
albumin, leukocytes, and fibrin factors. 

2. Fibrinous Inflammation. — The plasmatic and cellular exudate 
may form a fibrinous membrane on free surfaces or a network within 
the tissues; this is termed " fibrinous inflammation" because the most 
conspicuous physical change is the excess of coagulum. 

In purely fibrinous inflammations of serous surfaces there is a whit- 
ish or yellowish- white deposit of variable thickness which is more or 
less adherent to the underlying surface. When removed there may be 
seen beneath it a pronounced injection of the blood-vessels and rough- 
ness and rawness of the surface. This is due to beginning granulations. 
(See Repair of Wounds.) Microscopically, the fibrinous deposit con- 
sists of an irregularly arranged mass of fibrillar, granular, or homo- 
geneous fibrin, with leukocytes and endothelial cells (more or less 
degenerated) enclosed in the deposit. The fibrin may be found in star- 
like formations made up of a more or less degenerated central leukocytic 
mass and radiating threads of fibrin extending from it in every direc- 
tion. This may be significant of the liberation of fibrin ferment from the 
degenerating cells and consequent formation of fibrin about this as a 
center. Some authorities believe that fibrinous inflammation can never 
occur independently of destruction of fixed cells. In other words, they 
doubt the possibility of fibrin formation from purely exudative elements. 
Some experimenters have, however, described fibrinous inflammations 
of serous surfaces with an unbroken fining of endothelial cells under 
the fibrinous deposit, and have concluded that the fibrin is wholly exu- 
dative. It would seem that both processes might be responsible, for it is 
difficult to imagine exudation without thromboplastic substances or 
at least enough damage to the endothelium to liberate this activator of 
coagulation. Fibrinous inflammation in serous sacs is often associated 
with serous exudation, and the term serofibrinous is applied. In other 
cases (especially in peritoneal inflammations) the exudate is likely to 
become purulent — fibrinopurulent inflammation. Inflammations of the 
serous membranes are nearly always more or less fibrinous. 

3. Pseudomembranous or diphtheritic inflammation differs from the 
last in having associated with the coagulation of the exudate decided 
coagulation necrosis of the cells of the part inflamed. The difference is 
one of degree rather than of kind, and is largely dependent upon the 
character of the tissue in which the inflammation occurs. Diph- 
theritic inflammation occurs especially in the pharynx and larynx, where 
it occasions pseudomembranes (Fig. 31). This is most frequently due 
to the specific bacillus of the disease called diphtheria; but diptheritic 
inflammation may result from a variety of severe irritants, such as other 
bacteria, superheated steam, and chemical agents. The diphtheritic 
membrane consists of a network of fibrin or of homogeneous or granu- 
lar fibrin masses enclosing degenerated epithelial cells and emigrated 
leukocytes. Sometimes it is quite superficial, involving only the surface 



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A TEXT-BOOK OF PATHOLOGY 



layer of epithelium; at other times the whole depth of the mucous mem- 
brane is implicated. The former are sometimes called croupous and the 
latter diphtheritic false membranes. These terms, however, are ill- 
defined and objectionable. The use of the terms fibrinous and pseudo- 



Fio. 31. — Pseudomembranous or diphtheritic inflammation, showing the firm but fine 
fibrinous meshwork on the surface, lying upon an injected and infiltrated mucosa onl which 
the surface epithelium has disappeared and in which the glandular elements are somewhat 
degenerated. 

membranous, omitting croupous and diphtheritic as unnecessary, if for no 
other reason, is good practice. In any event it must be observed that the 
term " diphtheritic" as used in this place refers to a type of fibrinous 
inflammation rather than to a process due only to the diphtheria bacillus. 
This organism is the most frequent cause of such inflammation, but other 
agents, as before noted, occasion the same type of inflammatory lesion. 





INFLAMMATION AND REGENERATION 137 

4. Suppurative inflammation is characterized by unusual abun- 
dance of emigrated leukocytes and by the tendency to liquefaction. 
Bacteria are most frequently the cause; but it has been shown experi- 
mentally that croton oil, calomel, turpentine, and other substances are 



Fig. 32. — Purulent endometritis from a case of puerperal septicemia. 



capable of producing suppuration. Of the bacteria, the commonest are 
the so-called pyogenic staphylococci and streptococci; but numerous 
forms, not commonly pyogenic, may occasionally prove so. Such are 
the gonococcus, the Bacillus coli, and others. 



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A TEXT-BOOK OF PATHOLOGY 



The implantation of bacteria of suppuration at the point of disease 
may take place directly through wounds, or somewhat indirectly through 
the circulation, the micro-organisms having gained access to the system 
through small abrasions in the mucous membranes or skin. Some 
local injury may then serve to determine the suppurative inflammation 
at a given place. 

Recent studies ascribe to chemotaxis the important role in the 
action of bacteria in inflammation and suppuration. Either the prod- 
ucts of the bacteria or substances derived from their own protoplasm 
(endogenous substances) exercise a powerful chemotactic influence, and 
thus occasion the massing of emigrated leukocytes (Fig. 33). The 




Fig. 33. — Embolic abscess in the myocardium, showing accumulation of large numbers 
of leukocytes (Karg and Schmorl) . 

preponderance of cellular over liquid exudation and the consequent excess 
of leukoprotease over anti-enzyme prevent fibrin formation, or cause a 
solution of fibrin already formed and a liquefaction of degenerated tissue 
elements and cells. The sequence of events is as follows: bacteria 
directly implanted in the tissue or carried to the capillaries in the blood- 
stream first cause local cellular changes (degeneration or necrosis) ; then 
congestion and exudation of leukocytes and plasma occur around this 
focus; next more or less fibrin formation results from the exudation, and 
finally, after more and more leukocytic emigration, softening of the whole 
area completes the formation of pus. The essence of suppurative in- 
flammation is the excessive emigration of leukocytes, autolysis of local 
cells, and the failure of the fluid exudate to coagulate and form 
fibrin. The excessive leukocytic invasion is chargeable to inordinate 
chemotaxis due to the micro-organismal or other causes of the inflamma- 
tion or to their products (see page 126). 

Pus consists of a liquid part, the liquor puris, a modified blood-plasma, 
which differs from ordinary plasma in being less coagulable and in con- 
taining notable quantities of albumose (peptone) ; and a corpuscular part, 
consisting chiefly of polymorphonuclear leukocytes, more or less degener- 
ated, and usually, filled with neutrophilic granules; the nuclei may show 
some karyorrhexis or karyolysis. Nevertheless it is not possible to 



INFLAMMATION AND REGENERATION 



139 



identify these pus-cells absolutely. They often contain globules of glyco- 
gen and fat. Some proliferated connective-tissue cells or wandering 
cells may be added from the neighboring tissue, but these constitute 
but a minority of the whole number. 

Abscess. — When circumscribed suppuration occurs in the substance 
of a tissue or organ, the lesion is' called an abscess. This consists of a 
collection of pus which usually has a creamy yellow color, but may 
be variously altered by subsequent changes. The abscess grows by 
further liquefactive changes in the surrounding tissues because of the 
accumulation of leukocytes with their ferments when the serum from the 
neighboring vessels, carrying-anti enzymes, cannot penetrate the dense 
wall of leukocytes at the periphery. Around the abscess the tissues 
present an indurated zone or wall in which the proliferative changes and 
fibrin formation described as part of inflammation are conspicuous fea- 
tures. There are numerous round cells, differing from emigrated leuko- 
cytes and often showing mitotic figures in the nuclei, and there are new 
blood-vessels and beginning organization. (See Regeneration.) Fibrin 
in the form of interlacing threads or in masses, the product of plasmatic 
exudate and of coagulation necrosis, adds to the embankment. In 
slowly forming abscesses the surrounding wall of condensed tissue is 
often quite firm. This restraining wall was formerly erroneously regarded 
as a pus-producing membrane, and, therefore, called the pyogenic mem- 
brane. As a matter of fact, on the contrary, it represents the inflam- 
matory changes at the periphery of a suppurating area where the 
actively chemotactic effects of the pyogenic agent are sufficiently re- 
duced in activity that the liquefaction characteristic of pus formation 
is minimized in favor of coagulation and formative processes. 

Abscesses tend to soften the surrounding tissues in the direction of 
least resistance, and thus to break on the surface, discharging their 
contents by sinuous tracts or sinuses. This discharge not only evacuates 
the pus, but reduces pressure and permits a renewed flow of fresh blood 
through the so-called pj^ogenic membrane, bringing with it the anti- 
enzymes and bacterial antibodies of the serum. Sometimes the pus of 
an abscess becomes inspissated by absorption of the liquid part, and the 
residue undergoes various degenerative changes, such as mucous, 
fatty, or calcareous. At the same time the surrounding membrane 
may advance to complete organization, and thus encapsulates the 
abscess. 

Phlegmonous Inflammation. — Suppurative inflammation may have 
a less definitely circumscribed character than that seen in abscesses. 
It may take the form of a purulent infiltration in which the tissues are 
extensively infiltrated with emigrated leukocytes and more or less soft- 
ened by liquefactive processes, or by abundance of fluid exudate that 
does not coagulate. In other cases a nearer approach to the conditions 
seen in abscesses is observed when the purulent process spreads along 
planes of tissue or neighboring foci coalesce to form a diffuse suppura- 
tive condition. To this the terms phlegmon and phlegmonous inflam- 
mation are applied. 

Ulcer. — Suppurative inflammation with erosion of areas of the skin 
or mucous surfaces occasions ulcers. The floor of an ulcer has the same 



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A TEXT-BOOK OF PATHOLOGY 



histological construction as the wall of an abscess. In it may be seen small 
red points or granulations, which consist of loops of capillary blood- 
vessels surrounded by round cells. (The histology of granulation 
tissue is more minutely described under Regeneration.) 

The clinical features of ulcers vary widely. Sometimes rapid de- 
struction of the tissues causes large and spreading ulcers, called phage- 
denic. Others extend in one direction while healing in other parts, and 
are called serpiginous. The granulations may be too rapid in growth, 
forming red fungous masses (proud flesh) which fill up the ulcer. In 
other cases the ulcer remains dry and indolent, showing little tendency to 
heal. 

Some ulcers are not primarily of inflammatory origin. For example, 
the round or peptic ulcer of the stomach is formed by digestion, through 
the action of the gastric juice, of a part of the stomach which has be- 
come lowered in vitality or possibly necrotic. Similarly, the beginning 
change in the perforating ulcer of the foot in tabes and in decubitus (bed- 
sores and other forms of pressure ulceration) is not inflammatory, but, 
rather, necrotic. Secondarily, however, the necrotic tissues in these 
cases become active irritants and occasion true inflammatory ulceration. 

Suppurative inflammations of -serous membranes lining closed sacs 
cause collections of pus in the cavities. The pus usually contains more 
or less fibrin, and there is a fibrinopurulent exudate on the serous surface. 

Suppurative inflammation of the skin and subcutaneous tissues may 
be localized or diffuse. Of the localized type, there are various pustules, 
furuncles or boils, and carbuncles. A furuncle is a suppurative and ne- 
crotic inflammation beginning in one of the sweat-glands, sebaceous 
glands, or hair-follicles. A carbuncle is a more extensive but similar 
process beginning in several of the glands or hair follicles simultaneously, 
and causing considerable necrosis or gangrene of the skin and subcu- 
taneous tissue. 

5. Hemorrhagic Inflammation. — More or less diapedesis of red 
corpuscles generally occurs in inflammation; but sometimes the irritat- 
ing cause falls with such peculiar force on the blood-vessels or the 
general condition of the patient (cancer, tuberculosis, hemophilia, 
scurvy) is such that the exudate is unusually rich in red corpuscles. 
Certain micro-organisms (organisms of hemorrhagic septicemia) more or 
less regularly cause hemorrhagic inflammation. Intravascular throm- 
bosis and obstruction of capillaries with masses of micro-organisms play 
an important part in causing the hemorrhagic exudation. These are 
always serious inflammations, and .are to be distinguished from ordinary 
inflammations in which accidental hemorrhage occurs. Hemorrhagic 
inflammation, in a pathological sense, may be an early stage of other 
forms, particularly of the fibrinous variety of the lungs. There is 
severe congestion, diapedesis, and transudation of plasma, which almost 
at once make fibrin. This hemorrhagic state is transient and is not to 
be compared ; with the continued outpouring of blood in the hemorrhagic 
infections. The cause of the last is bacterial toxins acting upon vessel 
walls, decreasing their resistance. The effect is greatest where they are 
naturally thin, in a condition of stasis or already affected by local or 
general disease (syphilis). 



INFLAMMATION AND REGENERATION 



141 



6. Catarrhal Inflammation. — -This term is used to designate inflam- 
mations of mucous membranes. The character of the inflammation de- 




Fig. 34. — Acute catarrhal inflammation of the intestines, showing dense polynuclear and 
round cell infiltration, degeneration of the epithelium and a small hemorrhage. 




Fig. 35. — Acute bronchial catarrh, showing the escape of leukocytes from the submucous 
tissue between the epithelial lining cells (Thoma). 

pends to a large extent upon the individuality of the mucous membrane 
affected, differing greatly in the nose, throat, stomach, bowel, etc. 



142 



A TEXT-BOOK OF PATHOLOGY 



There is always considerable congestion of the mucosa, and generally a 
great deal of serous exudation, which is discharged from the surface as 
a rule, but is to some extent retained in the tissue, causing edematous 
swelling. This is especially marked when the submucosa is considerably 
implicated. The epithelial cells of the surface suffer degeneration 
(mucous or fatty) and necrosis, and are discharged with the serous 
exudate; they may be recognized as goblet-cells (mucous), or as granu- 
lar cells (fatty), or as fragmented necrotic structures. Coincidently 
with the serous exudation, and in greater measure after the latter has 
become less marked, leukocytes escape from the blood-vessels or emi- 
grate from their resting-places in the submucosa and make their way to 
the surface between the epithelial cells (Pig. 35). At this stage also 
mucus becomes a more or less pronounced feature in the exudate. 
There is little fibrin formation in catarrhal inflammation, since the 
exudate moves toward the surface and escapes. The features of this 
form are the superficial exudation and desquamation after degeneration. 
When fibrin appears this catarrhal form becomes pseudomembranous. 

When in great abundance (as in some nasal catarrhs) the process 
may be a purulent or suppurative one; more frequently there is suffi- 
cient mucus to require the term mucopurulent. Superficial erosions of 
the epithelium and hemorrhages are frequently met with. 

When catarrhal inflammations are chronic, there is usally consider- 
able productive inflammation, with consequent thickening, and later, 
when the new fibrous tissue contracts, there may be uniform thinning 
of the mucosa of irregularly distributed areas of hyperplasia intermixed 
with areas of thinning. In some cases, however, progressive atrophy of 
the mucosa occurs without previous productive changes. This is espe- 
cially marked in the bowel, where, doubtless, constant distention plays 
an important part. When the contractions of the fibrous tissue are 
irregular, the mucosa between the fibrous areas may be elevated, espe- 
cially if there is at the same time proliferation of the surface epithelium 
and the glandular elements in the mucosa. In such cases a granular 
surface or polypoid elevations result. These are common in the stom- 
ach and the bowels. 

7. Parenchymatous or Degenerative Inflammation. — This term may 
be applied to certain inflammations, such as forms of nephritis in which 
degeneration (cloudy, fatty, etc.) of the parenchyma cells is more con- 
spicuous than the exudative processes. The changes in the parenchyma 
in such cases are often secondary to the inflammation; in other cases 
they are precedent. Strictly speaking, the parenchymatous changes are 
not essentially a part of the inflammation, but in those cases in which 
much degeneration of parenchymatous cells accompanies inflammations 
the term " parenchymatous inflammation ' ' is convenient and expressive. 

8. Necrotic or gangrenous inflammations depend for their occur- 
rence upon the severity of the irritation or the state of the general system. 

9. Productive Inflammation. — In this form the proliferative changes 
predominate over exudation and degeneration. This may be due 
to the nature of the etiological factor, to peculiarities in the tissue reac- 
tion, or local conditions affecting the removal of the irritant. In all 
cases in which inflammation for any of the above reasons becomes 



INFLAMMATION AND REGENERATION 



143 



chronic the proliferative changes in the affected tissues become more or 
less predominating. Some degree of primary tissue destruction appears 
to be essential to the productive process, which, therefore, must be 
regarded as always reactive or regenerative. 

It is desirable to differentiate between (a) productive processes as 
the last stage of acute inflammation, (b) the newly iormed connective 
tissue as the result of acute inflammation, and (c) the progressive pro- 
duction of fibrous tissues as the result of continued irritation. The lines 
between the three are not sharp. The repair of serous membrane in- 
flammation may be a simple thickening of the layer itself, but if granu- 
lations attach two or more areas together, we have adhesions which are in 
excess and probably not necessary for the healing of the original defect. 
Thus, again, in cicatrices we have nature's expression of excessive pro- 
duction for repair. When the cause of the inflammation ceases the 
productive changes usually cease, unless the tissue already made acts 
as a foreign body and continues as a mechanical irritant. If it cease, we 
have a finished reparative process as the result of inflammation. Should 
the irritant continue its action, there is continued response as expressed 
in the infectious granulomata and chronic fibroses. The last are really 
chronic inflammations. 

Productive inflammation may effect other tissues than the fibrous 
connective tissues. Reference will be made to epithelial proliferation 
in the healing of wounds. Similar epithelial processes of greater activity 
or duration may lead to warty growths of the skin or polypoid 
outgrowths on the mucous membranes. In pharyngeal catarrhs consider- 
able proliferation of the adenoid tissues is not unusual. So also thicken- 
ing of cartilages, bones, or the periosteum is not an unusual result of 
inflammation of these structures. 

Repair of Wounds. — Productive inflammation is well illustrated 
in the healing of wounds. If the lips of a clean, incised wound are drawn 
together at once and kept closely apposed, rapid healing occurs, which 
is called healing by immediate union. In these cases a microscopical ex- 
amination shows slight exudation from the surfaces of the wound and 
proliferated connective-tissue cells. The epithelial continuity is restored 
by proliferation of the old epithelial cells. Should apposition be less 
immediate or less accurate, the amount of exudation is greater. If the 
wounded surfaces are examined twenty-four hours after the injury, they 
are found red and swollen and soon they become glazed in appearance. 
The microscopical features here are the same as in the case of healing by 
immediate union, excepting the amount of exudation is greater. Healing 
proceeds in the same way, but more slowly, and is called healing by first 
intention. In neither case is there gieat congestion. If the wound be 
irritated by foreign bodies or kept exposed, there will be seen o the sur- 
faces, after two or three days, small red elevations, known as granula- 
tions, which consist of loops of new-formed capillaries covered by 
emigrated and new-formed round cells, and sometimes (after longer 
intervals of time) giant-cells (Fig. 36). If to the above be added micro- 
organisms with their attraction for leukocytes, fluid pus will cover the 
wound, while in the surrounding tissue an active infiltration and exuda- 
tion will appear; this is then to all purposes an exudative inflammation. 



144 



A TEXT-BOOK OF PATHOLOGY 



Healing cannot be expected until defensive processes exceed irritative, 
that is until the mononuclear and fibroblastic stages are wholly effective 
in removing exudate and making connective tissue, whereupon epithelia 
or other structures may regenerate. So much damage has been done 
that connective tissue is made in excess and 
the overplus is seen in a cicatrix or scar. This 
tissue has the property of contracting and 
usually distorts and disfigures the part. It is 
composed of white fibrous tissue in dense 
irregular strands and contains relatively few fat 
cells. A scar is well supplied with blood and 
is pink or bluish at first, but when contraction 
occurs it becomes pale. This form of healing is 
called healing by second intention or healing by 
granulations. 

The formation of adhesions following in- 
flammation of the serous surfaces occurs in 
much the same way as wounds heal. The primary 
exudation is largely fibrinous and causes aggluti- 
nation of neighboring surfaces. Subsequently the proliferative con- 
nective-tissue cells, penetrate this fibiinoas exudate, as do new-formed 
blood-vessels (Fig. 37). Thus a union of vascular channels is effected 
between the adjacent inflamed surfaces, and organization follows. The 




Fig. 36. — Loops of blood- 
vessels in granulation tissue 
(Thiersch). 




Fig. 37. — Adhesive pericarditis, showing fibrin deposit, with new blood-vessels extending 

upward into it. 

same principles are involved as in the organization of a thrombus and 
then its canalization, in the latter case the capillaires formed for its 
nourishment enlarging and becoming patulous through its entire length. 
The factor involved is chiefly the demand by the newly formed tissue 
for blood supply. 



INFLAMMATION AND REGENERATION 145 

Precisely similar changes occur in the tissues surrounding a foreign 
body, as a piece of sponge or around a portion of dead tissue. In these 
cases the exudative and proliferated cells tend to penetrate into the for- 
eign mass, as occurs also in the organization of thrombi. There is in 
these cases a greater tendency to the formation of giant-cells than in 
ordinary granulations. Jf the foreign mass can be softened and absorbed, 
this gradually occurs, and later merely a scar will remain; if it cannot 
be absorbed, connective tissue eventually encloses or encapsulates it. 

General Fibrosis. — A tendency to widespread productive inflam- 
mation is noted in certain individuals. This affects the blood-vessels 
especially (general arteriocapillary fibrosis, general angiosclerosis), and 
also the liver (cirrhosis of the liver), the kidneys (interstitial nephritis), 
and other organs (Fig. 38) . Some form of degeneration or necrosis of the 




Fig. 38. — Chromic interstitial nephritis: great increase of connective tissue around the 
glomeruli, renal tubules, and blood-vessels; from a case of arteriocapillary fibrosis. 

parenchymatous cells is doubtless the preliminary stage in all of these 
cases. First the endothelia or the muscle cells are affected in the cases 
of blood-vessels; the hepatic cells in case of the liver; the epithelia of the 
tubules and glomeruli in case of the kidney, etc. The resulting fibrosis 
is, however, out of all proportion to any demonstrable change of paren- 
chyma. In some cases it is evident that the fibrosis is merely a com- 
pensatory regeneration to replace degenerated parenchyma and that the 
process is not primarily inflammatory, although some of the histological 
changes are akin to inflammation. There is a certain degree of general 
fibrous tissue increase in nearly all cases of marked senility which is in 
part a replacement overgrowth and in part the result of long continued 
intoxication or infection. It is asserted that the cause of degeneration 
of Jparenchyma cells may sometimes be repeated protein intoxication. 
(See Anaphylaxis.) 

Pathological Physiology. — Inflammation represents increased and 
altered activity of tissues as a result of irritation; its primary object is 
10 



146 



A TEXT-BOOK OF PATHOLOGY 



the removal of the irritant. It is a pathological state per se, but con- 
sidered from the point of view of its result (the removal or confinement of 
the irritant and the resulting tissue destruction) inflammation is essen- 
tially conservative and useful. In this process no new forces or activities 
are involved: the phenomena are all observed in normal tissues, though to 
a less degree and in more orderly behavior. The liquid and cellular 
exudation has its prototype in the formation of lymph and in the normal 
wandering cells of the tissues; the increased vascularity is the result of 
increased demand, and is abnormal in degree only; the cellular destruc- 
tion is an accentuation of the ordinary death of cells resulting from wear 
and tear, though the form of the cell destruction is hi ore violent and 
probably different; the postinflammatory regeneration is effected by 
karyokinetic multiplication of cells, as in normal tissues. 

In the destruction and removal of the irritant, phagocytosis (q. v.) 
is important; it is accomplished by the leukocytes, by endothelial cells, 
the wandering connective-tissue cells, and giant-cells. 

Though a local process, inflammation often has widespread results. 
The causes of the inflammation gain access to the blood via the lymph- 
vessels and regional nodes before a wall of fibrin and leukocytes has been 
built up around the inflamed locality. When once the local tissue reac- 
tion has developed and the lymph-nodes are prepared, further dis- 
semination is halted. The primary invasion of the blood-stream may 
be advantageous in stimulating antibodies, which can then be carried 
in the blood-plasma to the focus of infection. The products of tissue 
change (primary cellular necrosis, degeneration of the emigrated leuko- 
cytes, softening of the tissue and coagulated exudate) entering the blood 
may occasion fever and other evidences of toxemia. 

The functional activity of a part the seat of inflammation is often 
increased, though somewhat altered. An inflamed gland may pro- 
duce an excessive but abnormal secretion. In other cases functional 
activity is lessened; chronic inflammations almost certainly lessen 
functional power. Secondary parenchymatous changes, by altering 
organic action, may be highly injurious to the whole organism. 

Resolution after Inflammation. — In cases of trivial exudation the 
emigrated leukocytes and fluid exudate reenter the circulation directly 
or through the lymphatics. When the exudate is more abundant, the 
liquid elements may be removed in the same way, but the leukocytes 
first undergo degenerative softening and are reduced to the form of an 
emulsion, which is gradually removed by the mononuclears. In purulent 
inflammations the pus may be discharged through external openings or 
into cavities of the body or may become inspissated. (See Purulent 
Inflammation.) The degenerated parenchyma in inflammation may 
recover if the degeneration is not severe, or may be softened and removed. 
It is perhaps well to emphasize by repetition that the wandering mono- 
nuclear cells are great scavengers of effete cells, tissues and foreign 
bodies and that upon the fibrous tissue elements falls the burden of 
replacing lost supporting structures. When possible parenchyma is 
replaced by multiplication of adjoining cells; if this fail fibrous tissue 
elements may increase to make up bulk and to retain proper tissue 
pressure and balance. Upon the amount of damage will depend the 



INFLAMMATION AND REGENERATION 



147 



result, for when it was originally trivial no vestige may remain, when 
extensive a cicatrix results. 

Specific Inflammations or Infectious Qranulomata. — Tuber- 
culosis. — Structure and Evolution of the Tubercle. — When the tuber- 
cle bacillus is received into any tissue or organ, its first effect, according to 
the investigations of Baumgarten, is to stimulate or irritate the fixed con- 
nective-tissue elements and endothelial cells and cause a proliferation of 
round cells, which resemble in their abundance of protoplasm the epi- 
thelial cells and are, therefore, known as epithelioid cells. From other 
sources it is maintained that migratory cells are the precursors of this 
type. The evidence today would seem to be in favor of the older view 
for at least most of the epithelioid cells, but swelling of lymphocytes 
might easily give pictures similar to 
those in late inflammation. Fibro- 

blastic increase, late in the history of f ^ \:<!>f/)Ju^< 

the tubercle, would also support the < : t/^~7* f>, f v>, 

first explanation. These cells have /V 'C^J^v^/^^--^f^ \\ 
usually a single nucleus, of rather 
clear vesicular appearance, not deeply 
staining, and a relatively large amount 
of protoplasm. They may be pro- 
duced in greater or less abundance, 
as the first reactive change of the 
tissues to the irritation of the tubercle 
bacilli. Next there follows an in- 
filtration with leukocytes from the 
surrounding blood-vessels, and the 
focus of irritation thus becomes sur- 
rounded with numerous small round 

Cells, mostly mononuclear, with darkly Fig. 39. — Miliary tubercles in the 

staining nucleus and a small proto- ^oS^S 
pasmic body (Fig. 39). In more giant-cells within, 
acutely formed lesions polymorpho- 
nuclear leukocytes are more abundant. This leukocytic infiltration 
represents the reaction of the vascular system to the tuberculous 
irritation or infection. The number of small round cells varies greatly 
in different instances. Sometimes, as in certain tubercles of lymphatic 
glands, they may be relatively few, while the epithelioid cells are present 
in abundance. In other cases the small mononuclears are so quickly 
attracted and in such numbers that the tubercle seems composed of 
these cells alone, few epithelioid cells appearing in view. These 
tubercles are known as the " lymphoid." In the later stages the round 
cells may disappear by degeneration, exposing the previously hidden 
epithelioid cells. 

At the stage of the tubercle when it is composed mainly of epithe- 
lioid and lymphoid cells it appears to the naked eye as a grayish, some- 
what translucent, pearly body. It is avascular, no tendency toward 
formation of new blood-vessels being apparent. In the further evolution 
of the lesion degenerative changes take place. These are hyaline de- 
generation, coagulation necrosis, fatty change, and eventually a trans- 




148 



A TEXT-BOOK OF PATHOLOGY 



formation into cheesy material, the so-called caseous necrosis. This 
process, so common in a tubercle as to be helpful in diagnosis but not at 
all the last word in it, is the result of bacterial metabolism assisted 
by the lack of blood supply to the center of the growth. The bacillus 
produces unsaturated fatty acids which neutralize or inhibit the enzymes 
freed by cell death, which would otherwise liquefy and prepare for re- 
moval, cell detritus and fibrin. The absence of blood current favors 
the accumulation of this substance; the dense cellular infiltration at 
the periphery of the tubercle, and perhaps thrombosis as well, cause the 
local anemia. One of the first changes noted is a granular change in the 
cell protoplasm which lessens the affinity of the cell protoplasm and of 
the nucleus for ordinary stains. There may be seen among the cells of the 
tubercle here and there individuals which show this beginning necrosis. 
These are usually grouped in the center of the tubercle, though at times 
also at different points. The outlines of these cells become less distinct 



Fig. 40. — Large tubercle of the lung, showing chessy necrosis in the center; the epithe- 
lioid and giant-cells around the chessy center are more or less degenerated. 



and they are progressively less deeply stained, until with advanced 
necrosis the cell is broken down into particles or debris (Fig. 40). In the 
early stages of necrosis the epithelioid cells tend to form giant-cells either 
by coalescence of neighboring epithelioid cells or by division of the nu- 
cleus without division of the cell body. This is the Langhans' giant-cell 
with its nuclei arranged about the periphery. The giant-cell is not char- 
acteristic of tuberculosis, as it may be found in many of the specific 
inflammations and also in foci of chronic irritation due to foreign bodies, 
as well as in tumors. Their presence and especially their arrangement is 
however of great assistance in determining the probable nature of a 
tubercle, in which they may be very numerous at times; occasionally 
they are entirely lacking. The giant-cell falls an early victim to the 
advancing necrosis. Perhaps, in fact, the formation of the giant-cell is 
an evidence of beginning necrosis and the division of nuclei without 
division of the cell is an evidence of the degenerative change. As necro- 



INFLAMMATION AND REGENERATION 



149 



sis of the cell advances the protoplasm becomes granular and opaque, and 
eventually breaks down completely. This change usually occurs at the 
opposite side of the cell from that in which the nuclei are gathered; or in 
cases in which the nuclei are around the periphery of the cell the necrotic 
changes begin in the center. Finally, a tubercle undergoes almost com- 
plete necrosis and is transformed into a cheesy mass, the surrounding 
connective tissue perhaps still showing proliferative changes which may 
eventually cause encapsulation of the tubercle. Calcification may ensue 
in the cheesy mass and thus lead to permanent arrest of activity in the 
nodule. 

The foreign body tubercle, that due to pieces of silk, hairs, etc., usu- 
ally under the skin, differs from the specific kind in failing to undergo 
caseation, and in the prominence of connective-tissue new growth with 




Fig. 41. — Foreign body tubercle in subcutaneous tissue, showing foreign body (wood) in 
the center and an atypical giant-cell. 

some giant-cells. Tubercles arising from acid-fast organisms not the 
true tubercle bacillus are almost exactly like the specific tubercle and 
must be differentiated by bacteriological methods (Fig. 41). 

In the growth of tuberculosis the normal tissue elements of the 
part effected are pushed aside, or may be softened and destroyed by 
the morbid process. The connective-tissue fibers of the part, how- 
ever, are longest retained, and remain as a reticulum or tubercle stroma 
long after the other elements of the tissue have disappeared or been 
pushed aside. 

In soft tissues, such as the lungs, spread of tubercluous lesions is 
easy, and a diffuse inflammatory exudate may arise with only an occa- 
sional miliary tubercle. If several tubercles meet, their limiting walls 
may fu3e and a conglomerate tubercle ensue. A conglomerate tubercle 
may also arise by the transportation of organisms from the center of 
an already formed focus, through its outer zone, by means of epithelioid 
cells or lymph-currents. 

Tubercles tend to coalesce, forming larger tubercular masses, and 
sometimes distinct tuberculous tumors are so produced. In the lower 



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A TEXT-BOOK OF PATHOLOGY 




Fig. 43. — Miliary tubercle of the human form. 



INFLAMMATION AND REGENERATION 



151 



animals, particularly in cattle, such tuberculous tumors of the serous 
surfaces are not uncommon. They may simply stud the membranes, or 
they may hang as polypoid masses; the term " pearl disease" is applied 
to these cases (Fig. 42). Somewhat similar tuberculous tumors are met 
with in human tuberculosis, especially in the brain. As a rule, however, 




Fig. 44. — Tuberculous lymphatic gland: a, a, Lymphadenoid tissue; b, b f large round 
cells (epithelioid); c, c, large spindle cells (Ziegler). This is the diffuse form and bears 
resemblance to Hodgkin's disease. 

increasing areas of tuberculous disease of organs are only partly composed 
of tubercles, the bulk of the diseased area presenting evidences of ordinary 
or peculiar inflammatory changes to which the presence of the tubercles 
has stimulated the tissues. 

When the infection is very severe and the tissue soft, or even in firm 
structures if the resistance be low, an active inflammation without tu- 
bercle formation may arise. Epithelioid 
cells, a few mononuclears and leukocytes 
form the field which progresses in all di- 
rections and undergoes caseation. This 
is acute caseous tuberculous inflammation 
and may be seen in the lungs. 

A form of tuberculosis without the 
classical tubercle is seen at times in the 
lymphatic system when groups or strands 
of epithelioid cells course through the 
tissue, perhaps bordered by or inter- 
mingled with small mononuclears, but 
without giant cells or caseation (Fig. 44) . 

The tubercle bacilli in the earliest 
stages of the tubercle may be seen lying t 45.— Giant-cell containing 

7, ... , 11 ,, bacilli (from a photograph made by 

in the tissue and perhaps between the Dr. William M. Gray), 
epithelioid cells first formed. With the 

evolution of the disease they are more and more abundant, are largely 
within the cells, and the giant-cells in particular may contain large 
numbers (Fig. 45). As the necrotic changes increase > the bacilli become 
less conspicuous, and eventually none may be visible. The existence of 
the bacilli, however, cannot be doubted, since injection of portions of 
such tubercles produces the disease in guinea-pigs. 




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A TEXT-BOOK OF PATHOLOGY 



Syphilis. — Histology. — In syphilitic lesions of all kinds and in all of 
the stages there is a tendency to accumulation of round cells and pro- 
liferation of connective-tissue cells, the processes being first manifest 
around the smaller blood-vessels, but subsequently extending to other parts 
of the tissue. The walls of the blood-vessels themselves are frequently 
involved, and thickening of the inner or of all the coats may be observed. 
Complete destruction of the vascular channels is not rarely the conse- 
quence. Some authors locate the earliest changes in the small veins and 
lymphatics. In the subsequent course of the disease there is a tendency 
to the formation of distinct cicatricial connective tissue, giving rise to 
indurated scars, strictures, or diffuse sclerosis; and a less pronounced 
tendency to the occurrence of degenerations, mucoid and fatty, causing 
areas of degenerative softening. 

The Chancre. — The initial lesion first presents small areas of round- 
cell infiltration in the deeper layers o? the skin or mucous membrane 
and, as a rule, in the neighborhood of the blood-vessels. The connective 
tissue at the same time undergoes proliferative change, and spindle- 
shaped cells or irregular embryonal connective-tissue cells are found 
mingled with the round lymphoid cells, or surrounding foci of the latter. 
Giant-cells are rarely present. Thickening of the blood-vessels 
may be observed in the later stages or from the very first. The tissue 
elements of the skin and of the subcutaneous tissue are usually sepa- 
rated by infiltrating liquid, and the latter may loosen the tissues of the 
surface and cause exfoliation of the superficial epidermis, and thus lead 
to the development of the primary vesicle or the erosion so commonly 
seen. The induration of the chancie is probably the result of the sclero- 
sis of the vessels and the general connective-tissue hyperplasia, as well 
as in part due to the tense infiltration of serous liquid. 

It is characteristic of syphilis that the periarterial change occurs 
first, to be followed by the parenchymatous. This process may go 
on during all the secondary stage. Obliterating endarteritis is a type 
of change in syphilis that may occur at any stage. 

The Mucous Patch. — The condyloma latum is very similar in struc- 
ture to the initial lesion. There is, first, round-cell infiltration of the 
deeper layers of the mucous membrane, with serous exudation and 
erosion of the surface. Later, there is a tendency to connective-tissue 
hyperplasia, though this is less marked than in the case of the chancre. 

The histology of the macules, papules, vesicles and pustules of second- 
ary syphilis follows the type of lesion already stated. The vessels of the 
corium are dilated and surrounded by a mantle of round cells, while 
within there is usually some form of endothelial swelling or hyperplasia. 
When fluid occurs in the epiderm vesicles appear which may go on to 
pustules if mixed infection occur. Some forms proceed to the production 
of pronounced ulceration with fairly well formed crusts (rupia) in which 
the granulation tissue is thickly studded with small mononuclears. 

The Tertiary Lesions. — The gumma is composed in large part of 
round cells derived from the blood-vessels and proliferated connective- 
tissue cells, having a spindle shape or various irregular forms. Epi- 
thelioid cells are less abundant, and giant-cells, though cocurring at 
times, are usually few in number. Plasma-cells may be abundant in 



INFLAMMATION AND REGENERATION 



153 



syphilitic lesions, and mast-cells occur in small numbers. The blood- 
vessels are nearly always more or less affected, the intima being thick- 
ened and the adventitia being also involved to a variable extent. Peri- 
arterial changes are very conspicuous. There is some new formation of 
blood-vessels, the lesion in this respect differing from the nodular lesion 
of tuberculosis (Fig. 46). Secondary changes are almost always seen 
in gummata of considerable dimensions, being more diffuse and irregular 
than in tuberculosis. Among these may be recognized a gradual 




Fig. 46. — Gumma of lymph node. Central necrosis, few fibroblastic cells remain, periph- 
eral round cell infiltrate. 

necrotic transformation of the cells in the center of the lesion, with dis- 
tinct fatty degeneration or myxomatous change. The degenerated 
tissue may be infiltrated by leukocytes in a state of fair preservation. 
The differential diagnosis between a tubercle and a gumma is by no 
means easy, and there are cases in which it is well nigh impossible. 
Stains for the bacilli or the spirals should be used. 

In the diffuse tertiary lesions of syphilis the tissues of the affected 
organ are indurated, the connective tissue showing more or less pro- 
nounced hyperplasia. These processes cannot be certainly distinguished 
by their microscopical or general features from sclerosis due to other 
causes, unless there are associated miliary or massive gummata. 

Leprosy. — The nodule or leproma is a somewhat indurated growth 
resembling the tubercle, but differing from it in its greater vascularity 
and in the absence of the tendency to cheesy necrosis. Microscopically 
it is composed very largely of proliferated connective-tissue cells of dif- 



154 



A TEXT-BOOK OF PATHOLOGY 




ferent forms, plasma cells, and endothelioid cells. New blood-vessels are 
discovered in more or less abundance, the newly made tissue following 
their course, and a tendency to complete organization with the formation 
of fibrous tissue may be seen in the character of the cells and the presence 
of fibrous intercellular material. Elastic fibers degenerate. The bacilli 
occur within the cells and possibly also between them, arranged either 
singly, in pairs, or in bundles like wrapped-up cigars. They are always 
found in groups and usualfy in large numbers. They multiply within the 
cells, the protoplasm of the latter at the same time undergoing a process 
of swelling and degeneration. This at first spares the nucleus, but finally 
the nucleus itself is broken down and the cell is thus converted into a sac 

containing degenerated protoplasm and 
abundant bacilli (Fig. 47). The term lepra 
cell has been given to these. The bacilli 
also occur in the connective-tissue cells, in 
fatty tissue, and very often in the adventitia 
of blood-vessels. Giant-cells may be formed, 
though they are not frequent and are rarely 
typical, being much vacuolated. In a pure 
^ * lesion polymorphonuclear cells are usually 

^ " t^g* absent. Secondary infections or injuries may 

Fig^.— Lepm bacilli in ^ ea( ^ to suppurative or other forms of softening, 
a lepra cell (Kargi and and the final termination, either with or with- 
Schmori). ou ^. p rev i ous softening, may be cicatrization. 

In some instances the lesions of the internal 
organs met with in supposedly leprous cases, notably those of the lungs, 
intestine, kidney, and serous surfaces, have been found avascular, with 
more tendency to necrosis and containing more giant-cells; in some of 
these cases inoculation has shown that the lesions contained tubercle 
bacilli. Whether these were strictly tubercles, or whether they were 
lepromata with secondary infection with tubercle bacilli, cannot be 
decided. They were certainly not pure leprosj^ and more probably 
were purely tuberculous. 

The anesthetic areas and pigmented or light colored spots of the anes- 
thetic form present somewhat the same histological features as the leprous 
nodule, though in a diffuse form. Formerly these lesions were considered 
entirely the result of trophic changes. In these cases the more con- 
spicuous lesion is that of the nerves. These may show nodular thick- 
ening of the perineurium with inflammatory and degenerative changes 
of the nerve itself. The bacilli are present in these lesions, lying mostly 
within the cells of the perineurium. The effect is at first an irritation 
of the nerve and later a compression and degeneration of the nerve- 
fibers. Changes in the spinal cord have occasionally been discovered. 

Glanders. — In acute glanders there is a local necrosis of the fixed 
tissues with a fibrillary or granular degeneration sprinkled with chroma- 
tin debris and surrounded by a zone of polynuclear leukocytes. The 
elastic fibers remain in good condition for some time, but finally swell 
and degenerate. In chronic glanders the nuclei are retained for some 
time and the cells present an epithelioid type. Considerable connective 
tissue is formed. Polynuclear cells, but not typical giant-cells, may be seen. 



INFLAMMATION AND REGENERATION 



155 



Actinomycosis. — The first lesion of this infection is a simple sup- 
purative focus. This shortly assumes a tubercle arrangement by the 
appearance of giant- and epithelioid cells. It, however, soon proceeds to 
softening and central necrosis. The surrounding tissue is occupied by 
an active granulation process, losing all specific character except a tend- 
ency to fatty degeneration of the cells. The pus contains the sulphur 
granules of the organism, but the mycelium with its swollen end may be 
found penetrating the granulation tissue. 

The histological changes in other streptothrix infections — mycetoma, 
pulmonary streptothricosis — are essentially the same. 

Rhinoscleroma. — The histological lesions of this condition are usually 
quite specific, although some authors still express doubt of the etiological 
importance of the Bad. rhinoscleromatis. The specificity of this chronic 
granulation tissue lies in the large Mikulicz's cells, a form of plasma- 
cell with hydropic or hyaline degeneration and a relatively small nucleus. 
They contain the bacilli. 

Saccharomycosis. — This condition gives rise to nodular necrotic 
masses surrounded by irregularly placed abundant giant-cells and active 
connective-tissue formation in the immediate neighborhood. The 
masses grow actively and may form considerable tumors. The budding 
yeasts may be found in the pus and some are seen in the giant-cells. 
The more acute the process, the more necrotic. Chronic cases tend 
to show tumefactions. 

Sporothricosis. — The peculiarities of this granulation tissue consist 
in a diffuse growth of epithelioid and plasma-cells and connective tissue. 
There is no nodular growth. The new growth and its supporting struc- 
ture do not tend to undergo degeneration. 

Mycosis fungoides may be a granuloma. Its exact nature is as yet 
uncertain. Its discussion is found under the Tumors, p. 208. 

REGENERATION 

Definition. — The term 11 regeneration" is applied to the formation 
of new cells of tissues of the same kind to take the place of those de- 
stroyed. Regeneration may be physiological or pathological. The 
former is that which occurs in the normal life of the organism and by 
which the cellular wear and tear is counterbalanced. Pathological 
regeneration is the more massive and often atypical reconstruction which 
follows disease or injuries. Regeneration is one of the essential elements 
in inflammation, as has been shown in the preceding pages, but it is not 
always an inflammatory process. 

Etiology. — The cause or mechanism by which normal regeneration 
is brought about is more or less obscure. Cells have an inherent tendency 
to multiply, and this goes on to a certain point, at which the normal 
development is complete. This limit is probably maintained by some 
restraining influence, but the nature of this is unknown. In the skin 
and mucous membranes, where physiological regeneration is most active, 
new cells are constantly produced and the older cast off. In what manner 
the balance is so maintained that production and destruction keep their 
equal pace is as yet matter only for speculation. The idea of action and 
reaction occurs naturally to the mind, and it seems probable that the 



156 



A TEXT-BOOK OF PATHOLOGY 



reproductive processes are dependent in some way upon the loss of sub- 
stance. In some cases the normal restraining influence seems to be 
deficient and giant growth results. In all forms of normal or physio- 
logical regeneration the reconstructed cells are exactly like the pre- 
existing cells, and the status of the tissue is unaffected. In highly 
specialized cells, such as those of the nervous system, regeneration seems 
to be intracellular — that is, the cells are constantly rejuvenated by 
supplies of nutriment rather than by reproduction in toto. Where the 
destroyed cells cannot reproduce themselves, or at least do so at too slow a 
rate, a lower form of tissue, connective usually, assumes a condition of 
activity and replaces the lost bulk and tension. It may be said in general 
that the lower the type of cell in specialization, the greater its power of 
self -propagation by cell division. The reverse is likewise true. A cell 
will also reproduce better when young and in its normal position than 
otherwise. 

In pathological regeneration there seems to be abnormal stimulation 
of the reproduction of cells as well as a reduced restraint. It is not 
improbable that various toxic substances have the power of stimulating 
the formative process, though this has not been conclusively demon- 
strated. In all cases in which degeneration is due to mechanical, thermal, 
or toxic causes there is, first, destruction of cells, then regeneration. In 
such cases the relief from the accustomed pressure may serve as a with- 
drawal of restraint, but at the same time there is doubtless augmented 
formative energy. In other words, nature repairs defects in excess. 
The stimulus may be the same agency as that which caused the primary 
cell destruction, or it may be due to the influence of formative irritants 
derived from the dying and dead cells. The demonstration that micro- 
organisms are able to produce substances having a strong attractive 
or repellant influence upon leukocytes gives some warrant to the belief 
that similar substances are at work in the regenerative changes that 
follow bacterial diseases. In the case of tissue destruction due to other 
causes similar products possibly play a part. It seems fair to assume 
from the work of Loeb and Miescher and others that certain conditions 
involving oversupply of protein and some alterations in chemical reaction 
in functionating tissues may be sufficient cause for proliferation. If this 
be true of relatively normal tissues, somewhat similar conditions may play 
a part in the proliferative changes occurring in pathological states. 

Pathological Anatomy. — Insofar as the anatomy of regeneration is 
concerned, it may be considered as affecting the cells and the gross tissues. 
The cell, following its inherent power, reproduces by karyokinesis or 
mitosis, except in rare instances to be noted below. Cellular identity is 
retained, connective tissue cells never becoming glandular 
secreting elements. Amitotic or direct division occurs in certain forma- 
tive cells of the bone marrow, in tumors and, it has been claimed, in 
adult lymphocytes but this method cannot be said to represent the usual 
one followed in regeneration of the higher animals. It is the 
attempt in all newly formed tissues to replace as exactly as possible 
the structures that were lost but this is at times not successful because of 
interference by scar tissues, connective tissue elements growing more 
readily than parenchymatous cells. The grosser anatomy of a part 



INFLAMMATION AND REGENERATION 



157 



undergoing regenerative processes includes usually a growth of capillaries, 
the appearance of which frequently occurs before gland cells begin to 
multiply. 1 

Pathological Physiology. — Regeneration is the more or less effec- 
tive effort of nature to replace injured or excised tissue. The restoration 
is complete in proportion as the tissues lack in higher organization and 
differentiation. The younger the individual, the more complete the 
regeneration of his tissues; and the lower the type of tissue, the more 
complete will be its restoration. In glandular organs, though some pro- 
liferation of epithelial structures occurs, the new-formed glandular ele- 
ments are but little capable of glandular acitvity. Newly developed , 
nervous tissue is least capable of restoring the original function. 

Regeneration of Epithelium. — In its simplest form, as, for instance, 
after a very slight injury to the cornea, regeneration occurs by a direct 
replacement of the injured cells by multiplication of the cells of the 
same kind near the point of injury. The intact cells become some- 
what swollen, then undergo ordinary cell division, and new cells are 
formed. In the reconstruction of surface epithelium involving to some 
extent the underlying tissues, as in lesions of the mucous membranes 
or skin, the surface epithelium undergoes the same kind of multiplication 
as that just described, and the mass of new-formed cells dips down 
into the corium around the edge of the injured area. In the deeper tissue 
new formation of connective tissue takes place in the manner already 
described under the head Healing of Wounds, and to be presently 
discussed more fully. In the subsequent stages the redundancy of 
epithelium caused by the dipping down of the mass of new cells into 
the injured area is reduced by condensation and gradual disappearance 
of some of the cells, so that eventually the epiderm or the layer of epi- 
thelium on the mucous surfaces does not differ from that in the surround- 
ing parts. When large areas of epithelium have been destroyed the 
replacement of the epithelial covering occurs by gradual increase of the 
cells at the periphery of the denuded area, until in time the whole surface 
becomes covered. When skin-grafting is practised by the surgeon, a 
similar growth of the epithelial cells starts from each of the grafts placed 
upon the denuded surface. Structures lying in the mucosa, submucosa or 
corium as the case may be, are only reconstructed if some of their essen- 
tial parts be left; thus sebaceous glands and hair are not replaced if the 
whole gland and follicle are destroyed. The repair of defects in endo- 
thelial surfaces follows the same general laws as lately shown by Carrel. 
In lymph- vessels the endothelium may regenerate or may possibly be in- 
volved in connective-tissue formation. 

1 Abnormal Cell Division. — There are certain disorders of cell multiplication that 
may be here described. Karyokinesis, instead of being a regular process of division of 
the nucleus into two daughter nuclei, may proceed irregularly. Sometimes the process 
is asymmetric, i.e., does not lead to equal division; in other cases it is multipolar, several 
instead of two daughter nuclei resulting. Other less definite irregularities are some- 
times observed, and some have held that cell division may occur by a process of mixed 
karyokinesis and amitosis. It is important to recognize that some of the forms of 
nuclear degeneration (karyorrhexis, hyperchromatosis) may be mistaken for normal or 
abnormal karyokinesis. Pathological karyokinesis is most frequently seen in malig- 
nant tumors. 



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A TEXT-BOOK OF PATHOLOGY 



Regeneration of Fibrous Connective Tissue. — In all cases of exten- 
sive injury the connective tissues take an active part in regeneration, 
and in the case of highly specialized tissues new-formed connective 
tissue takes the place of the specialized tissue, which itself is less capable 
of regeneration. There is almost always an excess of cellular reproduc- 
tion and consequently an enlargement of the part affected by the in- 
jury. Subsequently the cells contract, and thus the bulk of the new 
tissue approximates that destroyed. The new tissue must, of necessity, 
be more firm, as a larger number of cells are condensed in the space 
previously occupied by a less number. 

The important processes in regeneration of the connective tissues 
are: swelling and multiplication of the connective-tissue cells, migra- 
tion of the new cells into the area of injury, and the formation of new 
blood-vessels. The old connective-tissue cells increase in size and then 
undergo division by mitosis of the nuclei. As a result, new cells of 
rounded outline and with rather pale nuclei result. These may remain 
at the point of their formation or may actively migrate, like leukocytes, 
toward the center of injury. Subsequently they 
tend to undergo a change of form, becoming 
ij? *ggP . elongated and spindle-shaped or irregular in 
. j& ; , . r ' 1 outline (Fig. 48) . It is these cells, and not the 

^ -- >5 polymorphonuclear leukocytes, which are active 

^ in the final restoration of the tissues, and the 
#^ <#' terms " formative cells" and " fibroblasts" are, 

^ ^** therefore, appropriate. It is believed by some 
Fig 48 —Fibroblasts observers that endothelium can go over into 
forming fibrous tissue connective tissue. It seems certain that such 
(Ziegier). ce \\ s have something to do with the organization 

of a thrombus. With continued irritation the 
cells change from a flat plate to almost a cubic form. When the new 
cells have been formed, increase of intercellular substance takes place. 
The fibrils may be derived from the cells themselves by separation of 
filamentous prolongations growing out from the pointed extremities of 
the spindle cells, or they may result from a cleavage of a homogeneous 
intercellular substance in which the cells are at first embedded. This 
intercellular substance doubtless is a product or a secretion of the cell. 
In either case the fibrils are essentially a result of cellular activity. In 
the later stages of connective-tissue regeneration the fibrils contract, 
and the tissue thus becomes more compact, especially when the amount 
of intercellular substance is excessive. Collagen and fibroglia fibrils are 
reproduced and at some places also elastic fibers. The cells at the same 
time decrease in size and some are so compressed as to be almost ob- 
literated. It is characteristic of new-formed connective tissue, how- 
ever, that up to the latest stages the tissue is more cellular than normal 
tissue. 

According to Marchand three forms of round or lymphoid cells are 
also represented in connective-tissue regeneration : one the small lymph- 
cell, and two called leukocytoid cells. One of the two is somewhat 
larger than the small lymph-cell, possessing a relatively palely stain- 
ing nucleus, and considerable slightly granular or vacuolated protoplasm. 



INFLAMMATION AND REGENERATION 



159 



This is the polyblast of Maximow and it may come from the blood- 
stream or the tissue cells. The third variety is'the plasma-cell, which 
has been described on p. 129. 

Giant-cells of the foreign body or proliferative type are common in 
regeneration, and they act as phagocytes to remove substances which 
are not dissolved. 

New formation of blood-vessels is an important factor in regenera- 
tion of connective tissue when the extent of injury has been consider- 
able. Repair of very trifling injuries, such as an incised wound followed 
by a close apposition of the injured surfaces, does not involve any new 
formation of blood-vessels, though the pre-existing vessels become some- 
what hyperemic. When the injury is more extensive, vascularization is 
a necessary step in the repair. The new 
vessels result from extensions from the 
pre-existing vessels (Fig. 49). The endo- 
thelium of the capillaries becomes swollen 
and here and there processes are sent out- 
ward. These may unite with similar pro- 
cesses from adjacent capillaries or from the 
same one at a point somewhat distant, and 
central vacuolization may convert the loop 
into a primitive channel which eventually 
becomes a fully formed capillary by mul- 
tiplication of the endothelial nuclei and 
formation of definite endothelial cells. 
Sometimes the new vessel is formed by 
parallel outgrowths from adjacent endo- 
thelial cells of the parent capillary, leaving 
a space between the new-formed cellular 
extensions. Such new vessels occur around 
the site of injury and project in the form of 

loops into the area of injury itself, being surrounded by the new- 
formed connective-tissue cells above described. Usually the area of 
injury is first filled with a blood-clot or coagulated exudate derived 
from the injured tissues. This forms a matrix in which the new-formed 
connective-tissue cells migrate and the capillary loops project. The 
clot or coagulated exudate is subsequently absorbed as the process of 
cellular replacement advances. The young connective tissue thus formed 
later contracts and the small blood-vessels are largely reduced by com- 
pression, so that the appearance of the tissue may become that of a quite 
avascular structure. 

In regeneration of connective tissues, elastic fibers are not observed 
in the earlier stages. Subsequently they are formed more or less abun- 
dantly. 

Regeneration of cartilage and bone takes its origin from the peri- 
chondrium in the former case and from the periosteum or marrow in the 
latter. The process begins as a proliferation of chondroblasts or osteo- 
blasts respectively, which have the power to lay down a matrix which 
attracts chondromucin or bone-salts, as the case may be. The adult 
bone and cartilage cells have not the power to regenerate. In both 




Fig. 49. — Formation of new 
blood-vessels, as seen in the tail 
of a tadpole (Arnold). 



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A TEXT-BOOK OF PATHOLOGY 



instances embryonal connective tissue, such as that which occurs in 
regeneration of fibrous connective tissues, is first formed. Later, in the 
case of cartilage, areas of homogeneous intercellular substance appear, 
and thus cartilaginous substance is developed. Very commonly, how- 
ever, regeneration of fractures of cartilages is mainly fibrous, and there 
may be little if any true cartilage. Regeneration of bone in the case of 
fracture proceeds in much the same fashion, an abundance of cellular 
tissue first appearing around the fractured ends of the bone, within the 
marrow cavity at the point of fracture, and between the broken ends of 
the bone. In this osteoid connective tissue branching and radiat- 
ing columns of rudimentary osseous tissue appear as a sort of network 
in which complete ossification occurs at subsequent stages. Later, 
much or all of the fibrous tissue around the fracture and within the 
marrow cavity is absorbed, and the repair of the fracture is made com- 
plete by thorough ossification of the part between the ends of the bone. 
When bone-salt deposit is deficient, cartilaginous union results. 

Regeneration of adipose tissue begins with a formation of fat-free 
cellular tissue but whether this be of a specific kind or not is as yet un- 
known. Some observers have maintained that fat cells are specialized 
while others believe that many cells may compose adipose tissue. At all 
events where it is destroyed, no globules are seen at first in the regenerated 
cells, these appearing quite late. 

Regeneration of Muscle Tissue. — Striated muscle is replaced by 
fibrous tissue where the damage is extensive and separates widely the 
remaining muscle. In less severe loss of substance, two processes engage 
in regenerating the part. The sarcolemma nuclei undergo proliferation 
by mitosis and seem to attract protoplasm to make new cells. Also at the 
ends of broken fibers an accummulation of granular protoplasm occurs 
and the old fiber seems to exhibit a hypertrophy. Both these new struc- 
tures assume an irregular cross striation. There is an attempt for the 
new elements to grow across the gap but unless this is small, the effort is 
usually ineffectual. Some authors have said that multiplication is by 
direct division but mitoses have been reported. 

Regeneration of smooth muscle by mitosis takes place in some cases 
(uterus), but connective-tissue formation occurs instead when the areas 
of destruction are large. Although proliferation has been reported in 
cardiac muscular cells, repair is practically always in the form of connec- 
tive tissue. 

Regeneration of Glandular Organs. — In epithelial glandular organs, 
such as the liver, kidney, mammary or salivary glands, considerable 
new formation of epithelial cells may take place. It has been taught 
that gland cells are replaced by tissue cells below the basement-mem- 
brane. This is undoubtedly incorrect. Glandular cells are recruited 
from glandular cells or occasionally from the cells of small ducts. In the 
liver there may be active proliferation of cells and formation of new 
biliary ducts. This is seen in experimental injuries and also in asso- 
ciation with some forms of cirrhosis. In the case of the kidney, re- 
generation may occur in the cells of the straight tubules, while in the 
mammary glands, salivary glands, and the smaller glands of mucous 
membranes new formation of acini and ducts proceeds from the smaller 



INFLAMMATION AND REGENERATION 



161 



excretory ducts of the affected glands. In this way an atypical glandular 
structure may result. This will be discussed under Adenoma. Skin 
glands and their outlets are regenerated if the fundal parts have not 
been destroyed by the surface damage. 

Regeneration of Nervous Tissue. — Nerve-fibers are capable of con- 
siderable regeneration, which proceeds within the sheath of Schwann. 
The medullary substance is differentiated within the sheath, and the 
new axis-cylinder is an outgrowth from the existing axis-cylinder or 
the nerve-cell. Regeneration of the nervous fibers in the brain and 
cord takes place to but a slight extent. Injuries here are usually re- 
paired by the formation of new connective tissue and regenerating 
glia. The large multipolar nerve-cells seem to be capable of intra- 
cellular repair after partial injuries, but complete regeneration is never 
accomplished. It is possible, however, that they may be capable of 
limited proliferation, as such cells occur in certain tumors. Neuroglia 
proliferates, but less readily than fibrous tissue. 

METAPLASIA 

This is the term applied to the transformation of one form of tis- 
sue into another without the intervention of a stage of regeneration 
by cellular multiplication. It is exemplified under normal conditions 
by the transformation of cartilage into bone. It occurs with great fre- 
quency under pathological conditions, and may be here described as a col- 
lateral or inferior specialization in a tissue of the same original character, 
for mutations of tissue types do not occur. Thus, cartilaginous tissue 
may have an abnormal deposit of bony salts, fibrous tissue may become 
bony or fatty or myxomatous, but these never become glandular struc- 
tures, nor does gland tissue ever become nervous tissue. The process 
may be a purely interstitial affair and the cells suffer secondary changes. 
In other cases of metaplasia the cells may be primarily altered, as when 
ordinary connective tissue is changed to fatty tissue. 

The process, except where accommodative or defensive, is not easily 
understood. Cells of the embryo destined to be epithelium are differ- 
entiated so that they may assume their adult normal form and func- 
tion; by metaplasia one type of epithelium may adopt the form and at 
times the function of another. The same facts are true for connect- 
ive-tissue cells. Fully differentiated fibrous tissue may become calca- 
reous without the agency of osteoblasts from bones, connective-tissue 
cells acting the role of the latter. 

Although it has been claimed that fat cells are descended from the 
mucoid embryonal cells, some observers seem to think that connective- 
tissue cells not descendants of these fetal elements may become fat 
cells by metaplasia. 

The metaplasia of epithelial cells, as, for example, a change from cylin- 
drical to squamous cells on the surface of mucous membranes, has been 
doubted by some authorities. They assume that such apparent trans- 
formations are due either to ingrowths of the new order of cells from sur- 
rounding areas or by enlargements of islets of mucosa covered with 
such cells. Experiments, as those of Fiitterer, however, indicate that 
11 



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A TEXT-BOOK OF PATHOLOGY 



metaplasia does occur. In this process not only the old epithelia are 
altered by the changed conditions, but the new-formed epithelia, under 
the altered conditions of environment, develop into the new order of 
cells rather than into the parent form. 

The causes of metaplasia are, naturally, changes in physical relations, 
including alterations of pressure and irritation, carrying with them some 
differentiation of function and changes in nutrition. Injury or chronic 
irritation may bring these factors into play. 

The term retrograde change (Ribbert) has been applied to an altera- 
tion of cells in which under pathological conditions a lower order of differ- 
entiation is assumed, but in which the new order of cells do not acquire 
specific characteristics of a different sort. Thus, cylindrical epithelia of 
glandular tubules may be changed to cuboid cells lacking the original 
functional characters and not possessed of a new function such as would 
be the case with squamous cells. Similarly, in the atrophy of striped 
muscle, non-striated, narrow fibers with abundance of nuclei give evi- 
dence of a retrograde change toward embryonal conditions. 



CHAPTER VI 



PROGRESSIVE TISSUE CHANGES 

This term may be used to designate pathological conditions in which 
there is a tendency to the formation of new and functionally active 
tissue. 

HYPERTROPHY 

Definition. — The term "hypertrophy" is applied to a pathological 
condition in which a certain part increases beyond the normal size, 
without marked alterations from the normal structure. The term 
hypertrophy is frequently used loosely to designate enlargements of 
various kinds in which but one tissue of an organ is increased, or in 
which there is deposit of abnormal exudate. Such instances are not, 
strictly speaking, cases of r^pertrophy. 

Etiology. — The causes of hypertrophy are quite numerous. In 
some cases there is a distinct increase of functional demand brought 
about in some way or other, as in the hypertrophy of the muscles of 
athletes; in the hypertrophy of a kidney after disease or removal of 
its fellow; or in the hypertrophy of a limb after injury to the opposite 
limb. The direct increased demand for work occasions the hypertrophy. 
Sometimes there appears to be a special tendency to hypertrophy, as is 
evidenced by the occurrence of congenital or hereditary giant growth. 
Most of these, however, are instances of peculiar and abnormal develop- 
ment, rather than of hypertrophy, the latter being a condition developed 
pathologically in parts previously well formed. Disturbances of the 
nervous system and internal secretions may play a part in the develop- 
ment of some hypertrophies, but these influences are obscure. Con- 
tinued congestion undoubtedly stimulates tissue growth, but this 
element is the means whereby hypertrophy is effected rather than the 
original cause. 

In the compensatory or vicarious functional hypertrophies we must 
assume that two factors are at work — first, the stimuli resulting from 
increased demand, and second, the adaptive mechanism of the part ad- 
justing reaction to stimulation. It may be further assumed that there 
is always a margin of safety between the work thrown upon a part and 
the limit of work possible. During continued activity the cell enlarges, 
for which it must have increased nutrition and some period of rest. 
Should the stimulation continue without rest and increased nutrition, 
degeneration may occur. 

Some of the hypertrophies, such as that of the breast during preg- 
nancy and lactation, are undoubtedly due to internal secretions, prob- 
ably of ferment nature. The hormones belong to this class. We may also 

163 



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A TEXT-BOOK OF PATHOLOGY 



include in a similar group the growth taken on by some organs, like hair- 
follicles and mamma?, at puberty. Derangements of the ductless glands 
may lead to hypertrophies, among which the most conspicuous example 
is acromegaly from disease of the hypophysis. 

Pathological Anatomy. — Parts the seat of genuine hypertrophy 
are uniformly increased in size. This is well seen in the condition termed 
''giant growth,''' or ''''gigantism.' 7 in which the bony framework and 
other tissues ma}* be uniformly affected, the individual growing to exces- 
sive size. Sometimes local giant growth of the skeleton and external 
tissues is observed, as in the case of one member or a single finger. This 
has often been found in corresponding members on the two sides of the 
body. In certain cases termed " hypertrophy.'' in which this designation 
is more or less justified, lack of uniformity in the increase of the organ or 
part affected causes irregular increase in size. Hypertrophy and hyper- 
plasia may be used by the economy to make up loss of bulk the result of 
disease. 

Histologically, hypertrophy may be simple or true hypertrophy, and 
numerical (hyperplasia). (See Fig. 13.) In the former there is in- 
crease in the size of the individual cells; in the latter the cells increase 
in number, though the individuals are not excessive in size, and, indeed, 
often smaller than the normal cells. In the hypertrophy of the uterus 
during pregnane}- and of the heart muscle in compensatory enlarge- 
ment, simple hypertrophy predominates. Hyperplasia is very com- 
monly a factor in hypertrophy of members, but may be so strictly 
limited to one tissue of an organ, notably the connective tissue, that the 
term ''hypertrophy" is in no way applicable. Between these extremes 
there are all grades of cases; in many of which it is difficult to determine 
whether the designation hypertrophy is applicable or not . In some cases 
the clinical designation hypertrophic enlargement is used, though the 
condition is strictly one of hyperplasia of the connective tissue, with a 
tendency rather to atrophy than hypertrophy of the proper substance of 
the organ. Instances of this are hypertrophic cirrhosis of the liver, 
some cases of hypertrophy of the heart muscle, etc. 

Pathological Physiology. — Hypertrophy results from an increased 
demand upon an organ or member, and leads to increased functional 
capacity. Thus, in the case of a diseased kidney, the opposite kidney 
may be capable of compensating for the deficiency: in the case of laborers 
the enlarged muscles may meet every demand made upon them. There 
are occasional instances of more or less genuine hypertrophy resulting 
from diseased conditions, in which the excessive functional capacity 
causes marked disturbances, as, for example, in case of enlargement of 
the thyroid gland. 

TUMORS 

Synonyms. — Xew Growth, Neoplasm, Pseudoplasm. 

Definition. — In its broadest etymological significance the term '''tu- 
mor'" designates an abnormal swelling in any part of the body. This 
definition, however, is not applicable to tumors in the ordinary sense. 
Inflammatory growths and collections, such as abscesses, hyperplastic 
deposits, and the like, are excluded. Pathologists, however, have al- 



PROGRESSIVE TISSUE CHANGES 



165 



ways found it difficult to construct an accurate definition for tumors or 
to draw sharp lines of separation between them and the inflammatory 
or infectious swellings that occur in various diseased conditions. An 
attempt to establish an ultimate boundary-line is evidenced by the 
term autonomous new groivths, applied by Thoma. This name is used to 
designate the supposed spontaneous origin of new growths and their 
independence of ordinary causes, such as are recognized in the production 
of inflammatory outgrowths and the like. It cannot be said, however, 
that tumors are causeless, and in the discussion of the etiology we shall 
have occasion to refer to certain definite factors known to aid in their 
production. It is true, however, that the growth of tumors is practi- 
cally always out of proportion to the amount of local irritation or to the 
severity of other factors that may be conceived as playing some part in 
the etiology; and in the great majority of cases the causes, whatever 
they may be, are obscure or unknown. A negative definition perhaps 
best suits for the delimitation of this term "tumor." Thus, we may ex- 
clude from the category of tumors all swellings in which some sufficient 
cause is discoverable, and include the apparently causeless growths 
among the true tumors. A further characteristic of tumors is their 
independence. Excepting the blood-supply, there seems to be no de- 
pendence on the organism in which they occur, and they contribute noth- 
ing to the continuance of its life and its integrity. Perhaps there is no 
one thing so characteristic of tumors, malignant ones especially, as their 
independent unrestrained growth without consideration of tissue relation 
or balance. In the development of the body and during the wear and 
repair incident to life, there is a nice adjustment of the units going to 
make up a part, while under neoplastic conditions, no attention is paid to 
the need of the locality or the organism as a whole, the physical arrange- 
ments and functions being destroyed as the tumor spreads in its growth. 

Despite all of these characteristics, there are cases in which pathol- 
ogists cannot determine positively whether certain growths are to be 
classified as tumors or some other conditions. 

Etiology. — A great number .of theories have been suggested to 
explain the causation of tumors most of which are based upon the as- 
sumption that the cause is the same for all. While such may prove to be 
the case, one must not lose sight of the different behavior of certain 
classes of new growths in malignancy and benignancy, nor fail to consider 
the possibility that several causes may be operative. 

Among the older writers there was a disposition to attribute the 
occurrence of tumors to a constitutional dyscrasia, or a diseased state 
of the fluids of the body, a cause as obscure as the tumor. There was 
also a school that looked upon tumors as hereditary but one can only say 
today that no positive proof of inheritance exists. There are certain 
cancerous families among whom the same or similar neoplasms have 
appeared in several individuals or generations but this would seem rather 
to be an expression of predisposition (q. v.) than direct inheritance. 

According to the late observations by Slye upon mouse tumors, neo- 
plasms represent "a manner of growth" transmissible to progeny in a 
Mendelian sense, the faulty character being dominant or recessive, so 



166 



A TEXT-BOOK OF PATHOLOGY 



that by proper mating it can be made to remain a dominant feature 
or to die out. 

Recently a number of more elaborate theories have been constructed 
which ascribe the growths to some form of disturbance of vital activity 
and of cell proliferation, without explaining the cause of such disturbance. 
For example, we may refer to the theory that tumors result from a retro- 
grade change in vital properties of certain cells, so that they tend toward 
the original characteristics of the germ-cells and multiply in a purposeless 
and indeterminate manner. This theory was based upon the fact that 
asymmetrical karyomitosis is frequently observed in tumors. It was 
assumed that in this unequal division of the cells the peculiar, differen- 
tiating qualities of the cell are cast off with the smaller portion, causing 
the larger, in the course of several generations, to become anaplastic or 
retrograded. It has, however, been shown that the same sort of asym- 
metrical mitosis also occurs in non-tumorous conditions; and an addi- 
tional factor that must enter into the theory, the nature of the stimulus 
that causes the anaplastic cells to proliferate actively, is wholly un- 
explained. 

Another theory would explain the occurrence of new growths some- 
what upon the basis of infection, assuming, instead of an exogenous 
infection with micro-organisms, an endogenous infection. This was sug- 
gested by the discovery of leukocytes within the tumor-cells. The 
author of this theory explains that in consequence of some thermic, 
chemical, or other irritation certain cells may become, so to speak, infec- 
tious, assuming the role of a sperm-cell and stimulating the adjacent 
cells to abnormal multiplication. Such theories, however, are entirely 
speculative, and leave the etiology as little settled as before. 

Virchow strongly advocated the theory of external irritation, and was 
able to cite numerous examples of tumors that had arisen in consequence 
of more or less definite traumatism. Thus, in cases of carcinoma of the 
breast, in the epithelioma occurring on the lips in pipe-smokers, and in 
the epithelioma of chimney-sweeps, there is at times a definite history 
of unusual irritation, and the relation of cause and effect seems easily 
traceable. It must be admitted, however, that there is some further 
underlying cause which renders one individual liable to tumor growth, 
while another is not thus predisposed, and though it is probable that 
some tumors owe their origin to irritation as the exciting cause, all 
cases cannot be thus explained. Insofar as a single trauma in the causa- 
tion of a new growth is concerned, the evidence today points chiefly to a 
coincidental relationship. Malignancy has followed a large burn or 
a contusion of an epiphysis, but here again the factor that permits the 
neoplasm is obscure. 

Cohnheim advanced the interesting theory that defective develop- 
ment lies at the basis of tumor formation. According to his theory, there 
are frequently small errors of development leading to the inclusion or 
misplacement of portions of the original blastoderm in the midst of tis- 
sues derived from a different layer of the embryo. These inclusions, or 
embryonic rests, are independent of the function of the part in which they 
lie, and are assumed to be liable to subsequent sprouting, with the con- 
sequent formation of tumors. There is evidence that this theory con- 



PROGRESSIVE TISSUE CHANGES 



167 



tains a certain measure of truth, and some tumors, as, for example, 
certain ovarian growths, tumors of the parotid region, and others, seem 
to originate in this way. The theory, however, is not by any means 
universally applicable, and it leaves unexplained the final proliferation 
of the embryonal rests that had previously remained dormant. The 
assumption, however, that such rests would quite readily take on active 
growth as a result of various simple irritations, or when the vitality of 
the part was stimulated, is less forced than that which would attribute 
such proliferative activity to cells in their normal relation to surrounding 
tissues. Similar conditions may be brought about by disease or injury 
of various tissues. This is the essence of Ribbert's " disturbance of tissue 
tension " theory. If certain cells or parts of the tissue are displaced 
from their normal relations to the surrounding structures, the same 
conditions are established as by the embryonal displacement of por- 
tions of tissue. Not improbably this sometimes occurs either as a 
result of accident or of disease, and subsequently the displaced por- 
tions may prove the starting-point of tumor growth. Some authorities 
have insisted upon this as a frequent occurrence and as explanatory of 
many tumors. Experiments have shown that certain types of epi- 
thelium (epidermis), both adult and fetal, as well as certain fetal con- 
nective tissues (cartilage), may be experimentally removed from their 
normal postion and implanted in another part of the same animal and 
still retain their potentiality of growth. Such transplanted fetal tissues 
do not continue to reproduce the fetal stage, but tend to reproduce the 
ultimate stage of the transplanted tissue. Furthermore, in no case has 
there been found any infiltration of surrounding tissues by transplanted 
tissue, nor any tendency to metastasis. All of this shows that there is 
something additional in the development of tumors beyond the mere 
dissociation of structures from the surrounding tissues. 

Hauser, believing that he noted an increase in the size of tumor cells, 
a richness of chromatin and abnormal mitoses, thought that the cells 
were of a new type while Hansemann went further and considered them 
a race that could only proliferate and had no specialization. Oertel also 
assumes the primary change to be in the nucleus, there being a removal 
of part of the chromatin. Adami's modification of Hauser's theory 
assumes that the cell which started the growth lost its specialization, 
but not its power of reproduction. The relief of other demands upon 
it permitted the cell to apply all its energy to the dominant remaining 
function and acquire the habit of growth. This theory is at least con- 
sistent with our knowledge that a tumor serves no useful purpose to the 
body. Yet it must not be forgotten that as far as we know tumor-cells 
are nourished and have a cell chemistry closely like normal cells. They 
are at least dependent upon the same pabulum, although the end-prod- 
ucts may be different. 

Recently an infectious character has been ascribed to malignant and 
benign growths, and there is no doubt that in certain respects tumors 
resemble infectious processes of definitely ascertained kinds. Their 
effect upon the general health and their tendency to metastasis are 
very significant facts. Furthermore, the discovery that various patho- 
logical processes characterized by nodule, formations resembling tumors 



168 



A TEXT-BOOK OF PATHOLOGY 



in gross appearance are, in reality, infectious growths lends color to the 
suspicion. The resemblance of such growths to tumors is, however, 
merely superficial. As far as metastasis is concerned, tumors differ 
notably from infections, for, in the former, parts of the growth itself 
are conveyed to some place at a distance from the starting-point, there 
to proliferate and occasion a metastatic nodule; while in the case of 
infections the micro-organisms alone are carried to the secondary situa- 
tion, where they occasion changes in the local cells similar to those found 
in the original focus. 

Numerous investigations have been made to determine a possible 
connection of bacteria with tumors. These have proved beyond doubt 
that no bacterium of ordinary sort has any such relation. The possi- 
bility of ultramicroscopical organisms and even of such as, through ex- 
cessive parasitic character, could not live except within cell hosts, has 
been considered. 

Secondary and accidental invasions of bacteria into tumors may 
occur, and sometimes confusion has been occasioned by this 
circumstance. 



Fig. 50. — The first three forms in this old illustration from Ruffer (1892) show 
changes at times encountered in tumor cells, formerly thought important but now 
questioned and believed to be degenerative in origin. The last figure shows phagocytosis 
of leucocytes by a tumor cell. 

Various investigators since Hanau have found it possible to trans- 
plant certain tumors from man to animals or from one animal to an- 
other. This has sometimes been interpreted as an evidence of the 
infectiousness of tumors, though with doubtful propriety, since the trans- 
plantation of the tissue from one site to another, like the phenomenon 
of metastasis, proves only the proliferative tendency of the cells of the 
growth and not, of necessity, any infectious origin. The transplantation 
of part of the tumor from one animal to another or from one part to 
another in the same animal does not differ from the transference of por- 
tions of the tumor to distant places in ordinary metastasis. 

The experiments of Rous have shown that certain tumors of the 
fowl may be transmitted to a susceptible bird by suspensions of cells or 
a filtrate from this suspension which has been passed through a porce- 
lain filter that would hold back bacteria. He assumes that for these 
tumors there is a contagium vivum. These viruses only produce the 
kind of tumor from which they come. 

In carcinomata and other epithelial new growths, as well as in sar- 
comata, certain forms of supposed animal parasites have been described. 
In 1889 Thoma found in the protoplasm and nuclei of carcinoma cells 
bodies which he regarded as coccidia; and about the same time Malassez 
and Albarran found similar structures in the cells of an epithelioma of the 
maxilla. Darrier found bodies of the same kind in Paget's disease of the 




PROGRESSIVE TISSUE CHANGES 



169 



nipple, and many subsequent investigators have described similar forma- 
tions. Among these supposed protozoan organisms some are intra- 
nuclear, some extranuclear, and some wholly extracellular. 

All sorts of bodies have been described in tumors, and to them their 
respective observers have clung tenaciously as the cause of neoplasms. 
They have no relation to the causation of tumors, for they have not 
withstood close investigation. Members of many protozoal and arthro- 
podal genera have been described, even to as large a parasite as Sarcoptes. 
Many of the smaller ones were doubtless artefacts or can be ascribed to 
the Chlamydozoa of Prowaczek. The larger ones were artefacts or acci- 
dental inclusions. We may still learn that such protozoan or metazoan 
organisms have something to do with neoplasms, judging from Fibiger's 
results, but we are not yet prepared to accept any of them as the cause. 
This important communication upon the relation of organized bodies and 
new growth comes from J. Fibiger, who found nematodes in a papilloma- 
tous glandular gastric cancer of wild rats. These nematodes are carried 
by the roach, Periplaneta americana, and can be transferred to unaffected 
rats, when, if the animal be susceptible (not all are), a carcinoma of 
constant type will be produced. 

Recently blastomycetes have been thought of some etiological im- 
portance in the causation of carcinoma, but a careful review of the 
literature is convincing that the evidence does not suffice to establish any 
such connection. Blastomycetes do not constantly occur in malignant 
tumors, and when present are not in such numbers or in such relation to 
the tissue as to establish an etiological significance. The lesions definitely 
known to be due to blastomycetes are of entirely different character 
from those of tumor growths, being strictly exudative and inflammatory, 
with proliferation of endothelium and connective tissue, such as occurs in 
infectious inflammations. The proliferation of epiderm seen in the 
blastomycetic skin lesions of man is entirely secondary to the chronic 
inflammation of the underlying tissues. 

Predisposing Conditions. — Whatever may eventually prove to be 
the immediate cause of tumors, it is certain that predisposing causes are 
often of great importance. The occurrence of certain forms of tumors 
in persons of advanced age and in persons whose vitality has been re- 
duced by disease gives evidence that a constitutional predisposition 
is sometimes requisite for the formation of the new growth. The nature 
of this vital defect has sometimes been speculated upon, and retrograde 
vital metamorphosis of the cells or other like changes have been assumed 
to occur. These theories, however, are purely speculative. In some 
cases there is evidence of a family predisposition, and heredity was 
formerly regarded as of great importance. While this element cannot 
be entirely denied, it has certainly been overestimated. 

While even the predisposing causes to neoplasms are illy understood, a 
few points may be mentioned. Young persons are more often affected 
with mixed tumors and sarcomata while atypical epithelial new growths 
are more common in adults and elderly persons. New growths of organs 
peculiar to sex are common at the period of their normal retrogression. 
There are certain occupations which seem to favor the development of 
tumors, probably by reason of some mechanical or chemical irritant 



170 



A TEXT-BOOK OF PATHOLOGY 



admitted to the body by the work entailed; they are exemplified by cancer 
of the bladder in aniline workers, pulmonary cancer in metal workers and 
weavers. 

The Structure of Tumors. — In their histological structure tumors 
do not differ absolutely from healthy tissues. In all cases they conform 
more or less with the structure of some one or more tissues. The cells 
composing tumors invariably represent some one or several types of 
normal cells, though they may differ in being larger or smaller than the 
normal cells, or in resembling embryonal or undifferentiated elements. 

It may be said that the tissue from which a tumor arises is revert- 
ing to a state from which perfect differentiation into the normal adult 
structures cannot or does not occur. They have not lost all differ- 
entiation or specialization, since glandular tissue will always produce 
tumors with a glandular basis, but what is lost keeps the tissues near 
the parent or embryonal cell type. 

Not infrequently asymmetrical and otherwise abnormal mitosis of the 
cells is observed. It is important to note that such mitoses are not con- 
fined to tumors, but occasionally occur in inflammatory and infectious 
cellular proliferations. It cannot be stated that there is any character- 
istic or pathognomonic picture of a tumor cell although within certain 
limits the trained eye may detect such things as hyperchromatosis, 
irregularity of the nucleoplasm and abnormal relation of the nucleus and 
protoplasm. It is however in the arrangement of cell and stroma or in 
the appearance of cells not properly belonging in the tissue under exami- 
nation that neoplasms are recognized. 

In the arrangement of their cells tumors differ greatly from normal 
tissues, and they may be described as being atypical proliferations as far 
as their organic or tissue arrangement is concerned. The orderly dis- 
position of cells and stroma or intercellular substance seen in the normal 
tissues and organs is wanting, particularly in the tumors in which organic 
arrangement is simulated. There may be in some cases entirely typical 
glandular acini, but the relation of these to each other and the absence 
of regularly disposed excretory ducts render the tissue, as a whole, 
atypical. 

In the histological examination of tumors it is customary to find 
scattered through the stroma and between the tumor cells various forms 
of leukocytes, especially the polymorphonuclear forms, and lympho- 
cytes. The imperfect development of the walls of blood-vessels of 
tumors permits of ready emigration of leukocytes, and there is, there- 
fore, in practically every tumor a certain amount of leukocytic infil- 
tration. Sometimes leukocytes are found in enormous numbers; and 
when a tumor undergoes inflammatory change, massive accumulations 
and abscess formations may be met with. Plasma-cells, which are prob- 
ably altered lymphocytes, are sometimes conspicuous, and mast-cells 
(basophilic granular cells of doubtful significance) are sometimes found 
in benign as well as in malignant tumors. They are frequently abundant 
near the edges of the growth. Eosionphilic leukocytes are occasionally 
quite numerous. The leukocytes are often found within the tumor 
cells in the form of inclusions. These, doubtless, have been mistaken 
for parasites in some instances. 



PROGRESSIVE TISSUE CHANGES 



171 



The blood-vessels of tumors have comparatively fragile and poorly 
developed walls. In the malignant growths or rapidly developing tumors 
of any sort the vessels are mere spaces between the tumor cells, with 
little attempt at the development of firm walls. Tumors do not appear 
to have special nerves. Lymph-vessels are variable. In some they are 
well developed, having been included and modified from pre-existing 
ones ; in others they are entirely lacking. 

Regenerative changes are constantly met with in tumors. In this 
way the connective-tissue framework of the growth is formed just as 
such tissue is normally produced, and in this process elastic as well as 
ordinary connective tissue may be formed. In rapidly growing malig- 
nant tumors the framework of the tumor is, for the greatest part, derived 
from the pre-existing connective tissue of the affected part, and only 
in very small measure from regeneration of connective tissue. While 
the newgrowth usually employs the connective tissue as a stroma, it 
would seem that at times some influence is brought into play whereby the 
supporting cells and fibers take on abnormal multiplication and partici- 
pate in the tumor growth; thus we sometimes see a sarcoma added to a 
carcinoma. 

The structure of tumors is always closely related to that of the tissue 
from which it springs, a primary tumor invariably growing in a part in 
which there is tissue of the type simulated by the tumor, and it is from 
this tissue, doubtless, that the tumor takes its origin. A connective- 
tissue growth invariably springs from a part in which connective tissue of 
some form has pre-existed, and epithelial growths, from a part in which 
there has been epithelium. Transformation of one variety of tissue into 
another variety, with the production of a heterologous tumor, does not 
occur. This statement, though applicable also to secondary tumors, is 
sometimes difficult of demonstration from the fact that the secondary 
growths lake origin from cells transported to the seat of the metastatic 
growth, though not normally found in the part in which the secondary 
tumors have arisen. The occasional discovery of a primary tumor in a 
locality in which the form of tissue composing the tumor does not occur may 
be explained upon the assumption (based on some actual demonstrations) 
that embryonic rests had been deposited at the seat of the tumor by 
faulty development. 

The Shape of Tumors. — This depends to a large extent upon 
their manner of growth, their situation, and the influence of surround- 
ing parts. We may distinguish, first of all, between circumscribed and 
infiltrating growths. The former may be of various shapes, but are dis- 
tinguished by their sharp delimitation and often by the existence of a 
distinct capsule; the latter are indeterminate, and the extent to which 
they involve the healthy tissues canot be accurately determined. Cir- 
cumscribed tumors usually grow centrally or in an expansive manner, 
the new cells being produced in the interior and gradually pushing the 
older parts outward toward the surrounding tissues. The infiltrating 
growths are eccentric in development, and may result from a gradual 
extension of parts of the periphery of the original growth, or by the 
development of secondary nodules in the neighborhood which become 
confluent with the original mass. Of the circumscribed growths, we 



172 



A TEXT-BOOK OF PATHOLOGY 



may distinguish small nodules of spherical or ovoid form buried in the 
substance of the tissue or projecting from some surface as more or less 
hemispherical elevations. These may be large or small, and the terms 
miliary, tubercular, nodular, and the like are employed to designate the 
individual grades. When a tumor projects from the surface in such 
a manner that the projecting part is larger than the part between the 
projection and the surface of the body or the organ involved, the term 
fungiform or fungoid tumor may be applied, while in the cases in which 
the new growth is attached by a more or less narrow pedicle the name 
polyp or polypoid tumor is applicable. Wart-like growths are known 
as verrucose or papillary tumors, and those in which a distinct cauli- 
flower form is developed are called dendritic. 

The Number of Tumors. — Primary tumors are usually solitary 
at their onset, though examples of multiple primary growths, such as 
carcinoma involving both breasts simultaneously, or simultaneous 
appearance of carcinomata or sarcomata in different parts of the mucous 
membrane or elsewhere, may be observed. In these cases it is often 
likely that there was a single tumor at the very onset, with secondary 
growths originating -before the primary growth had reached any con- 
siderable magnitude. Primary benign tumors are usually solitary, but 
sometimes may be found in considerable number, and there may be 
enormous numbers scattered in various parts of the bod}'. Thus, in 
cases of multiple enchondromata or multiple fibromata the number may, 
from the first, be very great. 

Secondary tumors are usually multiple. In most cases the number 
of nodules found postmortem or during life is considerable, and some- 
times they are so numerous that large portions of the body may be 
literally studded with new growths. This is seen very well in the sec- 
ondary sarcomatous or carcinomatous nodules involving the peritoneum 
and the other serous surfaces, in which cases the degree of involvement 
is equalled only by that seen in nriliaiy tuberculosis. 

The rate of growth of tumors is extremely variable, but in general it is 
more rapid in highly cellular growths, slower in fibrous growths. There 
are however no rules by which one may construct the course of develop- 
ment. The rate of growth in malignant tumors is increased by injur}*, 
pregnancy and poor nutrition of the body. Benign tumors do not seem 
to grow so well when the nutrition is reduced by poor food or interference 
with their blood supply. Variations or intermissions of progress are 
sometimes observed, such as in tumors of the stomach. 

Instances of multiple primary tumors of different kinds are on record. 
For example, carcinoma and sarcoma may occur in the same individual 
as can epithelioma and adenoma. 

Pathological Physiology. — -In most cases tumors take no part in 
the functional life of the part in which they occur or of the individual: 
What influence they may bear to the general metabolism is as yet prac- 
tically unknown. Cases, however, are recorded in which large lipo- 
matous or other tumors have been found to suffer practically no change, 
while the individual in whom they occurred was undergoing progressive 
emaciation from starvation. That there is a certain amount of function, 
however, in some cases is shown by the fact that biliary pigment is 



PROGRESSIVE TISSUE CHANGES 



173 



detected in the cells in certain carcinomatous tumors of the liver, or 
abortive milk formation in cancers of the breast. It may be that the 
want of proper organic arrangement, and particularly the lack of excre- 
tory ducts, accounts for the lack of function; but, whatever the cause, 
it is certain that, as a rule, the functional activity is practically nil, 
or at all events perverted. The occurrence of large quantities of glycogen 
in certain tumors is perhaps of interest as indicating an attempt at 
functional activity, but is more probably significant only of active 
proliferation. With very few exceptions it may be said that tumors are 
entirely parasitic, living at the expense of the organism and contributing 
nothing to its development or nutrition. 

Certain tumors disturb the general health. This result may be 
due to secondary degenerative or inflammatory changes dependent 
upon lack of nutrition or upon irritation and bacterial infection. The 
progressive cachexia of carcinoma is still unexplained, though in some 
cases hemorrhage and interference with organic function play a part. 

The chemical constitution of tumors and the relation this bears to 
the body in general and to the changes in body fluids are subjects that 
have had very important advances in the past few years. They have 
led to better understanding of the place of a tumor in the body, if not 
to its etiology. As has been said, the chemistry of tumors is closely like 
that of the tissue from which they spring. This is also true of metas- 
tases. There has been no isolation from tumors of substances that are 
peculiar to them in general or to any particular variety. Because of 
their high cell content some tumors contain much nucleoprotein, but 
this will vary as the parent tissue varies. The digestion products of 
these proteins are abundant because autolysis is active within tumors. 
Glycogen also accumulates in tumors because of lowered cellular ac- 
tivity. It is, of course, in highest amount in tumors, the original tissues 
of which naturally store it. Fat on the other hand is low in growing 
tumors but when quiescent or degenerated, it appears; lecithin seems to 
follow the reverse course. Enzymes of the parent cells are retained in 
some neoplasms. 

The inorganic elements are present in the proportion of the proteins 
that they help to form, and not specifically otherwise. 

Enzymes are said to be more abundant in tumors than in normal 
tissues, and the extensive autolysis of new growths certainly bears this 
out. It may be that the cachexia of cancer patients is due to a constant 
dissemination of the products of autolysis. Some observers assert that 
the ferments are different or peculiar to tumors, but this is not proved. 
Tryptic action is very prominent; so much so, indeed, that carcinoma 
patients develop a high antitryptic power in the blood. Many tumors 
have the power of continuing the natural internal secretions of the parent 
tissue. Thus, thyroid and adrenal tumors and their metastases may pro- 
duce colloid and epinephrin respectively. 

Some of the products of tumor growth and extracts of the new tissue 
have hemolytic properties, but the exact relation of this power to anemia 
and cachexia is not understood. Metabolism is essentially the same as 
in wasting disease in general, there being an excessive excretion of pro- 
tein degradation products and mineral salts except the chlorids. 



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A TEXT-BOOK OF PATHOLOGY 



Tumors fail to set up any constant immune bodies that protect the 
system against them. The normal blood has a low anticancer-cell 
power and blood-serum of cancer patients has a lower value. Immunity 
tests, such as complement fixation and precipitation, are sometimes 
present, but too variable to permit any conclusions as to their value for 
diagnosis or relation to etiology. It is interesting to note that experi- 
mentally inoculated tumors are at once surrounded by lymphocytes 
and that injections of these cells increase the resistance of the animal, 
while on the other hand destruction of lymphocytes favors the new 
growth. 

Tumors may be classified as benign or malignant, characters which are 
in part clinical, in part strictly pathological. Certain growths of a kind 
usually called benign may obstruct organ passages or bleed frequently 
and give rise to a condition threatening life. Metastasis is not unknown. 
A truly malignant tumor on the other hand is one that is destructive and 
infiltrative, that gives the peculiar chain of signs known as tumor ca- 
chexia, that disturbs local function, that tends to recur after removal 
and that sends out metastasis, or some combination of these characters. 
Certain tumors are peculiarly infiltrative, notably carcinoma, in which 
spread they burrow along organ passages or tissue clefts, penetrate 
lymphatic, venous or even arterial channels, and grow at the periphery. 
Others are well outlined or even encapsulated but may burst their limiting 
membrane and become infiltrative. During infiltration, which is espe- 
cially marked in rapidly growing tumors, ulceration and necrosis are 
common while the tissue about an encapsulated mass degenerates 
from pressure. 

The cachexia of malignant growths is probably the result of infection 
of ulcerated surfaces and of anemia, but no peculiar poison is known to be 
the cause of it. Benign tumors may compress some vital organ and lead to 
a cachectic condition. The disturbance of local function is accomplished 
by infiltration or destruction of vital parts. Postoperative recurrence 
of a tumor takes place when some cells have been left behind. This is 
understood the more readily in infiltrative new growths when one 
imagines delicate strands of tumor cells, extending through the muscle or 
fascias, too fine to be seen by the naked eye; recurrence in suture holes is 
not at all infrequent. 

Before discussing the subject of metastasis, a word might be added as 
to the pathological meaning of malignancy. The more nearly a tumor 
represents adult differentiated tissue the more benign it usually is, while 
the more atypical the cells and anatomy the more malignant and self- 
propagating the new growth. Benign tumors, especially myomata, may 
actually change their character in rare instances, taking on a sarcomatous 
nature, thereafter following the behavior of the latter type. 

Metastasis is the development of a new tumor by dissemination of 
cells, or masses of them, trom the original growth through blood or lymph 
channels. Transfer may also occur by apposition of tissue as, after the 
rupture of malignant cystomata of the ovary tumor masses may extend 
over the whole peritoneum. 

The entranee of tumor elements into the vascular channels is the result 
of the invasive and destructive character of the neoplasm. In sarcomata 



PROGRESSIVE TISSUE CHANGES 



175 



for example the blood vessels are usually of very delicate structure, even 
being made up at times of a single layer of endothelia through which it is 
easy for a tumor cell to pass. Masses of sarcoma are not infrequentry 
seen in the intima of veins. Carcinomata have a tendency to spread into 
lymph channels and thus to lymph nodes. The foregoing are the usual 
methods for these two classes to disseminate but one occasionally sees 
secondary growths that seem to have disobeyed this rule. 

However the spread occurs, the travelling cell settles at some narrow 
point of the channel and there begins to proliferate, itself giving rise to the 
new tumor, for the local cells do nothing but supply stroma (see definition 
of embolism and metastasis, p. 70). Perhaps not every cell which is 
loosened from a tumor sets up a metastatic nodule, it being thought that 
many are, when settled, immediately surrounded by fibrin and then die. 
On the other hand it has been suggested that a small injury, causing endo- 
thelial proliferation and organizing thrombosis, may favor the settling 
and proliferation of a tumor embolus by supplying a ready-made stroma. 

The new growth set up by such an embolus attempts to reproduce the 
architecture of the original but usually fails to do so completely and may 
become more atypical than the primary tumor. Thus the metastasis of 
scirrhus breast cancers simulate adeno- or simple carcinomata. 

The distribution of a metastasis will depend in a measure upon the 
direction of the blood or lymph channels. Thus axillary glands are 
affected in mammary cancers, the liver in gastric cancers, while from 
sarcomata the lungs are common secondary seats since the emboli tra- 
verse blood vessels. There may, however, be individual or peculiar seats 
of secondary growths which seem to depend upon a predilection for 
certain tissues; the most notable example is bone metastasis from pros- 
tatic new growths. Retrograde metastasis also occurs. 

Tumors have been known to disappear spontaneously. This is 
rare in human beings, but is commoner in animals suffering from either 
spontaneous or experimental tumors. The cause is not known. Tumor 
cells are susceptible to mechanical influences when directly applied. 
They are more susceptible to x-rays and direct sunlight than normal 
cells. These agents destroy the vital ferments, but not the autolytic 
ones. Pressure upon and injury to a tumor seems to favor metastasis. 

The terms primary and secondary tumors refer to the original and 
the metastatic growths respectively. 

Classification of Tumors. — No very satisfactory classification 
is possible at the present time, and it is unlikely that any will be con- 
structed until more definite knowledge regarding the etiology is obtained. 
The older classifications were based upon the shape, the physical proper- 
ties, or the nature (whether destructive or harmless) of various forms, 
forms. Virchow offered a classification based on the histology of the 
new growths (histogenetic classification). According to this classifica- 
tion, fibroma, osteoma, chondroma, lymphoma, and sarcoma are included 
under the heading of connective-tissue tumors or tumors reproducing 
more or less accurately connective tissues. The different forms of tumors 
comprising the group are distinguished by their resemblance to one or 
another of the forms of connective tissue. Among the epithelial growths 
are papilloma, adenoma, and carcinoma, and in the same group should 



176 



A TEXT-BOOK OF PATHOLOGY 



be placed glioma, which, though it superficially resembles connective- 
tissue tumors and arises from the neuroglia, a tissue resembling connec- 
tive tissue in function, is really an epithelial growth, as the neuroglia is an 
ectodermal derivative. Among the tumors reproducing muscle tissue 
are the two forms of myomata — the leiomyoma and rhabdomyoma. 

This classification is eminently satisfactory in some cases, but fails 
in the case of mixed tumors containing a variety of tissues and in which 
the primary or essential constituent is not always obvious. Thus, in 
papillomata it is sometimes difficult to determine whether the growth 
was originally epithelial or originally of connective-tissue type. 

Recently it has been suggested (Mallory) that a more careful study 
of the histological differentiation of the cells and intercellular substance 
may serve as a basis of classification of tumors. Three forms of fibrils, 
called neuroglia, myoglia, and fibroglia fibrils, have been distinguished, 
and have respectively been found in gliomata of various types, in leio- 
myomata, and in connective-tissue growths, including fibromata, fibro- 
sarcomata, and spindle-celled sarcomata. The fibrils differ sufficiently 
to form the basis for the recognition of the character of the cells from 
which they originate, irrespective of the rate of growth or physical 
properties of the tumor. 

Other pathologists have grouped tumors according to the embryo- 
logical derivation of the tissues from which the new growths originate or 
of the tissue composing the tumor. It is perhaps wisest to attempt no 
classification of any kind, and in the following sections we have ar- 
ranged the various tumors according to their histological characters, fol- 
lowing in a general way the adult tissue types without attempting to 
establish groups. 

Connective-tissue Tumors 

:. FIBROMA 

Definition. — A fibroma is a tumor composed of connective-tissue 
cells and fibers resembling those seen in fibrillar tissue. 

It is derived from mesodermal cells which have the power to produce 
various kinds of fibrils. It varies from a slowly growing tumor composed 
of fibers almost exclusively up to rapidly growing new growths composed 
of cells, with little tendency to proceed to fiber formation. In the lat- 
ter case it approaches a sarcomatous nature. 

Etiology. — The causes of fibroma are as obscure as those of tumors 
in general. There are many facts, however, which point to 
the importance of irritation or injury as exciting causes. Among these 
may be mentioned the development of peculiar forms (keloids) in scar 
tissue and the resemblance of these tumors to spontaneous fibromata, 
and the appearance of fibrous nodules in the skin at points of friction 
or definite pressure or in places irritated by discharges. 

It is impossible to draw sharp lines between fibromata and hyper- 
plasias of connective tissue following irritation. In the skin and super- 
ficial tissues there occur hyperplastic connective-tissue processes,' con- 
stituting elephantiasis, which in some cases are distinctly the result 
of irritation, and in other cases seem purely spontaneous. The ele- 



PROGRESSIVE TISSUE CHANGES 



177 



phantiasis of tropical countries, often due to occlusion of the lymphatic 
channels by filarial and the thickening of the skin and adjacent con- 
nective tissue of the legs around old ulcerations or eczematous areas, are 
instances in which distinct irritation is the cause. On the other hand, 
congenital elephantoid conditions of the skin are seemingly spontaneous 
or causeless, and some of the cases in later life have the same char- 
acteristic. The diffuse hyperplasias of the viscera, though often dis- 
tinctly inflammatory, may appear without adequate discoverable cause, 
and, according to the view of some authorities, are to be looked upon 
as diffuse fibrosis or fibromatosis, rather than as inflammatory condi- 
tions. In ordinary cases of sclerosis of the organs the connective-tissue 
growth is entirely diffuse, but thickenings may occur in certain situa- 
tions, and the resemblance to tumor formation is then much more 
striking. This is sometimes the case in the liver, but particularly in 
the kidneys. In the breast there are cases in which no dividing line 
can be drawn between chronic interstitial mastitis and fibroma. The 
microscopical appearances are practically identical. A distinction, if 
any can be made, is based upon the nodular character and spontaneous 
origin in the one and the opposite conditions in the other. 




Fig. 51. — Hard fibroma (Warren). Fig. 52. — Soft fibroma of the subcutaneous 

tissue. 



Appearance. — The naked-eye appearance of fibromata is usually 
quite characteristic. The tumor may be hard (Fig. 51) or soft (Fig. 
52), according as it resembles dense or loose connective tissue in struc- 
ture and according to the amount of edematous liquid or associated 
myxomatous degeneration of the intercellular substance. The growth 
is more or less rounded and usually enclosed in a distinct capsule. In 
the substance of organs it is spherical or tuberous, arid when near the 
surface projects more or less. When it springs from a mucous or serous 
membrane or from the skin the weight of the tumor may gradually lead 
to a polypoid formation. Some of the fibromata of the skin are arbores- 
cent or dendritic in form, and keloids are frequently irregular or star- 
like in outline. The rounded and encapsulated tumors may be 
lobulated, though more frequently they occur in a uniform mass. 

12 



178 



A TEXT-BOOK OF PATHOLOGY 



Seats. — The points of origin from which fibroid tumors arise are 
very numerous, though they always spring from pre-existing connect- 
ive tissue. Among some of the more common localities may be men- 
tioned the subcutaneous connective tissue, the submucous tissue, the 
periosteum of bones, tendons and tendon-sheaths, and the fibrous 
covering of nerves. Of the internal organs, the uterus, the ovaries, the 
kidneys, and heart muscle are the most important. Less frequently 
fibromata are found in the serous membranes of the chest and abdo- 
men or of the central nervous system. Nasal polyps are not infrequently 
of fibromatous nature although overgrowth of the mucosa may obscure 
this and give the impression that it is the principal part of the mass. 
Fibromata of nerve sheaths often cause numerous nodulations along the 
course of nerve trunks; they are considered later. 

The mammary gland presents several interesting forms of inflam- 
matory or fibromatous new growth. First, there is a diffuse form of 
interstitial mastitis in which the entire breast becomes indurated; this 
is distinctly inflammatory. In other cases nodular or lobular areas of 
thickening occur, and in these the evidences of inflammatory action 




Fig. 53. — Intracanalicular fibroma (Perls). 



are sometimes obscure or wholly wanting. Some of these are certainly 
instances of true fibroma (fibroma mammas nodulum). In still another 
group of cases of fibromatous proliferation of the connective tissue 
projects into the tubules and acini of the gland, pushing the epithelium 
before it and sometimes sprouting or proliferating in polypoid form 
within the tubules. The gland in such cases may present a striking 
macroscopical appearance on section. Numerous cystic formations may 
be visible, with projecting dendritic formations within, causing an appear- 
ance somewhat like that of a section through a cauliflower (Fig. 53). 
Microscopically, the proliferations of the connective tissue between 
the tubules and projecting within the tubules constitute the charac- 
teristic features. The term intracanalicular fibroma has been given 
to such cases. Obstruction of the tubules in certain areas may lead 
to very marked cystic distention. 

Structure. — The definition explains the structure of fibromata- 
On section through the body of the tumor the fibrous nature may be 
revealed by a distinct concentric or radiating striation, particularly 



PROGRESSIVE TISSUE CHANGES 



179 



in the case of hard fibromata. The softer varieties are much less likely 
to present this feature. The color is usually gray or whitish, and may 
be glistening when there is mucous degeneration, or yellow in the case 
of associated fatty tissue. Microscopically, a striking feature is the 
connective-tissue cell, which is rounded, star-like, and branching in the 
softer tumors, and compressed, spindle shaped, or elongated in the case 
of the hard varieties. It is probable that these are but gradations of the 
growth of the same cell but some tumors stay soft and highly cellular 
while others develop fibres very rapidly. The intercellular substance 
is composed of a fibrillar network and homogeneous or granular material 
traversed by thin-walled blood-vessels, ofttimes having merely an en- 
dothelial coat. The parallel and wavy bundles of fibrils are the most 
conspicuous feature of hard fibromata. In softer varieties the fibiils are 
less often in bundles, and are twisted or irregularly curled. The fibrillar 
substance may be so closely packed that the intercellular substance has a 
glistening, hyaline appearance. This is very marked in keloids. Some- 
times actual hyaline change affects the fibrils. Cavernous dilatation 
and rupture of the vessels may cause a distinct hemorrhagic appearance 
of the section, but such conditions are rare. 

A true keloid is a fully formed connective tissue tumefaction without 
a capsule and tending to show hyalin degeneration. It is commonest 
in negroes. The epidermal layers and papillae are correctly preserved. 
A false keloid arises in scar tissue. It is apt to show a limitation, but 
not by a distinct capsule, and the epidermis and papillae are absent or 
distorted. 

Secondary Changes in Fibroma. — In some cases embryonal 
round cells may be abundant and a distinct sarcomatous transforma- 
tion of the tumor may occur. This, however, is rare. In other in- 
stances, as has already been remarked, myxomatous tissue may be 
conspicuous, and all grades of transformation, from a pure fibroma 
to a pure myxoma, may be met with, especially in the case of soft 
fibroma. Fatty degeneration of the cells and lipomatous infiltration 
or associated lipoma are also frequent. These forms, the myxomatous 
and lipomatous, are particularly frequent in the submucous and sub- 
cutaneous connective tissues. Calcareous change occurs in large fibro- 
matous tumors, particularly in those of the uterus, and very rarely true 
ossification has been reported. Less commonly association of fibroma 
with other forms of tumor growth is found. Among these the com- 
bination of fibroma with leiomyoma is usual in the uterus. 

Small fibromata about nerve-endings may be hard or soft. Some 
arise from the connective tissue of the nerve-sheath or from Schwann's 
membrane. A kind occurring on the skin in disseminated form is 
called molluscum fibrosum. There is also a painful variety upon or 
near nerve-endings. The nerve-fibers pass through or are caught by 
the fibroma and are not themselves changed. 

Nature. — Fibroma is essentially a benign tumor, though recurrence 
occasionally takes place after removal, this being particularly the case 
with keloids and some of the polypoid growths of mucous membranes. 
In some of these instances there is undoubtedly a resemblance to sar- 
coma, if not actual sarcomatous transformation. As a rule, fibroid 



180 



A TEXT-BOOK OF PATHOLOGY 



tumors are destructive only in so far as they are capable of producing 
mechanical injury by pressure. The growth of the tumors is usually 
exceedingly slow. Metastases of pure fibroma do not occur, and the 
mass does not recur if removed completely. 

MYXOMA 

Definition. — Myxoma is a tumor composed of connective-tissue 
cells and an intercellular substance containing mucoid material in more 
or less abundance. The gelatinous substance of Wharton in the um- 
bilical cord and the vitreous humor of the eye are normal tissue types 
which myxomata resemble in their structure. 

Etiology. — The causes and the nature of myxomata are prac- 
tically the same as those of fibromata, and intermediate forms make it 
difficult to draw a sharp line between the two. Less frequently myxo- 
mata are sarcomatous growths with myxomatous change. 

Appearance. — A typical myxoma is a soft, more or less flabby 
growth, enclosed by a capsule and having a rounded outline. It may 
project from the surface of the body or of an organ as a hemispherical 

elevation, or may hang by a narrowed 
pedicle in the form of a distinct polyp. 
The latter is frequent in the mucous 
membranes, but may occur in the 
skin as well. Sometimes the tumor 
is tabulated, and the lobules may be 
visible or may be easily felt. Oc- 
casionally myxomatous growths are 
diffuse, having no capsule and marked 
by .no definite limits. 

Seats. — Among the common situa- 
tions are the subcutaneous and sub- 
mucous tissues and the connective 
tissues of certain organs, notably the 

Fig. 54.— Myxoma, showing stellate mammary glands. They may OCCUr 
cells separated bv a gelatinous (mucoid) , , „ . , 

intercellular material. along the course of nerves, and m the 

brain or the spinal cord. They some- 
times spring from subserous tissues, notably from the inter auricular 
septum and valves of the heart. The tumor may be solitary or, like 
fibroma, may be met with in numbers. Congenital myxoma has 
frequently been found. 

Structure. — Microscopically, the characteristic features are stellate 
or spindle-shaped connective-tissue cells which lie within a matrix of 
myxomatous material (Fig. 54). The latter is homogeneous or slightly 
granular, and somewhat refractive to light, giving the- surface a glisten- 
ing quality. The cells themselves may be entirely normal young 
connective-tissue cells, or they may present evidences of fatty degenera- 
tion. Round, connective-tissue cells are met with in some instances, 
either scattered through the tumor or in certain areas, and may be so 
abundant as to justify the term "myxosarcoma." The vascular supply 
is usually poor, and the blood-vessels resemble those of fibroma in being 
only partially developed. Association with fibroma and lipoma is fre- 




PROGRESSIVE TISSUE CHANGES 



181 



quent. Cartilaginous tissue may be found in myxomatous tumors of the 
parotid gland or testicle, and in these cases the myxomatous portion is 
rather an association than a degeneration of an original chondroma. 
Myxomatous degeneration of chondromata, osteomata, fibromata, and 
sarcomata is, however, a frequent occurrence. 

Nature. — Myxoma is benign like fibroma, but recurrence is not in- 
frequently observed, and in a few instances metastasis has been reported. 
In these cases the growth was doubtless sarcomatous, with associated 
mucoid tissue. When myxoma becomes sarcomatous the cellular 
content increases and the mucoid material is absorbed. The growth of 
myxomata is slow. 

LIPOMA 

Definition. — A lipoma is a tumor composed of fatty tissue like that 
of the normal subcutaneous tissue. The epiploic appendages of the 
intestines are the normal type which lipomata resemble. They are 
derived from the fat cells and not from fibroblasts. The fat is the same 
as natural subcutaneous adipose tissue in chemistry, except that the 
lecithin is somewhat less in amount. 

Etiology. — There seems to be a tendency, consisting perhaps in some 
derangement of the trophic nervous system, to the growth of these 
tumors. It is difficult at times to draw a sharp line between circum- 
scribed lipomata and diffuse fatty growth. Localized fatty or myxo- 
lipomatous accumulations in myxedema and a curious and apparent^ 
causeless deposit of fatty tissue sometimes observed in the subcutaneous 
tissue of the neck in men, represent the border-line between lipomata 
and ordinary obesity. Some individuals have a marked liability to 
constant overgrowth of fat in different parts of the body, and the term 
''lipomatosis" is not inapplicable. This fatty growth does not appar- 
ently depend upon the character or quantity of food, nor even upon 
sedentary life in some cases, but rather on an obscure tendency to 
adipose accumulation. The importance of the hypophysis and gonads 
to such conditions has been the subject of much fruitful investigation 
in recent years. 

Traumatism seems to play no part in the etiology of lipoma, 1 hough 
fatty infiltrations are prone to occur around areas of injury or disease 
and in degenerated organs. 

Appearance. — Lipomata are usually circumscribed and encap- 
sulated tumors having a lobulated character, the latter .being due to 
septa of connective tissue. On the surface of the body they appear as 
somewhat hemispherical elevations which may reach enormous propor- 
tions. Rarely they become polypoid. In the interior of the body, as, 
for example, when they arise in the submucous or subserous connective 
tissue, they are very frequently, though not always, polypoid. Some- 
times they become detached and may be retained in one of the cavities 
of the body as free bodies. On section, the appearance is that of fatty 
tissue, though in some cases it is more firm from the association of fibrous 
tissue, and in other cases less firm from the nature of the fatty tissue 
itself or from associated myxomatous change. Lipomata may be soli- 
tary tumors or there may be many. As a rule, they appear in adult 



182 



A TEXT-BOOK OF PATHOLOGY 



years or middle life, but congenital lipomata are not very rare; occa- 
sionally they are found to begin in childhood. 

Seats. — Among the situations in which lipomata occur the most 
common are the subcutaneous fatty tissue of the back, shoulders, 
buttocks or limbs, the submucous and the subserous tissues. They 
may arise either in the normal fatty tissue or in connective tissues in 
which fat is not normally present. Some authors, however, deny the 
possibility of lipomata arising excepting from pre-existing fatty tissue. 
Of the organs, the mammary gland and the kidney are most frequently 
involved. There is a symmetrical arrangement of painful lipomata in the 
condition known as adiposis dolorosa, probably a nervous disorder or 
connected with the endocrine system. 

Structure. — Microscopically, lipomatous tumors resemble the 
normal fat. It is notable that the cells are larger — that is, contain more 
oil — than the normal fat cells, and this is strikingly the case in some 
instances, but is not always demonstrable. The vascular supply is about 
the same as in normal fat, though occasionally large vessels with thin 
walls are seen. Associated myxomatous or fibrous change ma3 r cause a 
variation of the microscopical appearance. Lipomata may undergo 
softening from necrosis, but more frequently become calcareous in part 
or completely. 

Nature. — This is the most benign form of tumors. Recurrence 
after more or less complete removal does, however, at times occur. 
A lipoma is dangerous only from its weight or position. It does not 
contribute to the support of the sj^stem in case of starvation. 

XANTHOMA 

Definition. — This term is applied to two possibly distinct though 
similar forms of new growth. The xanthoma, vulgare or palpebrarum 
occurs most frequently in the eyelids and may be confined to that 
situation. The growth appears in the form of flat elevations of a yellow 
color. Generalized xanthoma beginning about the eyes is less frequent. 
Xanthoma diabeticorum is a similar affection of diabetic patients. It 
occurs at a more advanced age, is more distinctly inflammatory, the 
masses are more rounded, and the eyelids and face are rarely affected. 
Xanthoma is frequently associated with hepatic disease. 

Structure. — The histology of xanthoma is that of modified fatty 
tissue. It resembles embryonal adipose tissue, and there is usually 
more or less round-cell infiltration as well. It lies chiefly in the corium, 
but the subcutaneous tissue may be involved. The large vacuoles contain 
cholesterol esters. The facts that these masses are not very destructive, 
are frequently absorbed, and often associated with an increase of choles- 
terol in the blood, have led most observers to consider them as infiltra- 
tions and not tumors. 

CHONDROMA 

Definition. — A chondroma is a tumor composed largely or entirely 
of cartilage. The parent cell is, of course, the chondroblast in the 
perichondrium, a fibroblastic cell which has, in addition, the power to 
lay down a ground substance of chondromucin. When this predominates 



PKOGRESSIVE TISSUE CHANGES 



183 



in tumors they have a hyaline appearance, but when the fibers pre- 
dominate the resulting mass follows the white fibrous or yellow elastic 
■cartilage types. It is difficult to draw a sharp line between outgrowths 
of cartilage from existing cartilage or bone due to irritation from definite 
and independent tumor-like growths. A group of cases of intermediary 
character is that including cartilaginous nodules formed in tendons of 
muscles subjected to frequent irritations, as in the deltoid muscles in 
soldiers carrying heavy arms, and in the adductor muscles in the thigh 
in horseback riders. In these cases normal connective tissue seems to be 
directly transformed into cartilage, though the influence of irritation 
is undoubted. 

Etiology.-^A congenital disposition, sometimes hereditary, is un- 
questionably present in certain cases. Virchow maintained that chon- 
dromata often spring from remnants or islands of cartilage left in ab- 
normal situations, as in the midst of bone, as the result of imperfect fetal 
development. The same explanation would account for parotid chondro- 
mata on the assumption that parts of the branchial arches are misplaced 
and remain in the substance of the parotid gland. Other evidences of 
the truth of the theory are the frequent occurrence of chondromata at 
the epiphyseal ends of bones, and the appearance of such growths in 
early life and especially in rachitic individuals. Direct traumatism is 
sometimes the cause of cartilaginous outgrowths from bone, particularly 
when fractures have occurred. 

Appearance. — Two distinct forms may be considered, and these 
are somewhat different in appearance. They are: (1) cartilaginous 
outgrowths, ecchondroses or ecchon- 
dromata, and (2) cartilaginous tumors 
or chrondromata proper, originating 
in non-cartilaginous tissues. 

Ecchondromata present them- 
selves as encapsulated, rounded, or 
somewhat irregular outgrowths from 
cartilages. Sometimes they are wart- 
like in form, and may occur in rows or 
groups. They may be firmly attached, 
or may be loosely united to the 
cartilage from which they spring. The 
most frequent (though not strictly 
neoplastic) are the outgrowths in the FlG> 55 ._chondroma of the thumb 
articular cartilage occurring in chronic (Warren), 
arthritis, particularly in arthritis de- 
formans. Occasionally they become detached after their formation, 
and in the joints may thus become free bodies. More characteristically 
tumor-like ecchondromata originate from the surfaces of the laryngeal 
cartilages or from the costal cartilages. 

Chondromata proper most frequently occur in bones or the perios- 
teum, and have a rounded or lobular appearance. 

Chondromata springing from the inner surface of bones (possibly 
originating from the marrow itself) may grow uniformly by repeated 
or constant proliferation and occasion globular swellings of the affected 




184 



A TEXT-BOOK OF PATHOLOGY 



bones (Fig. 55). The true bony covering becomes more and more thin 
until it may actually be perforated. 

The true chondromata are usually rounded bodies of dense elastic 
consistency and the pale blue color of cartilage; they present lobular 
irregularity when they reach considerable size, the lobules being sepa- 
rated by connective tissue, carrying blood vessels whence the nourishment 
of the tumor comes since capillaries do not penetrate the islands of 
cartilage cells unless a sarcomatous or osteomatous change supervenes. 

Chondromata are usually hard, though secondary softening may 
occur. In cases in which association of mucoid, sarcomatous, or other 
soft tissue is present the consistency is correspondingly less. In some 
cases central softening leads to cystic formation. The liquid in the cyst 
is more or less turbid and occasionally sanguinolent. 

Seats.— Ecchondroses and chondromata, for the most part, take 
their origin from bone, cartilage, or periosteum. The ecchondromata 
originate from the perichondrium rather than from the cartilage itself. 
In some cases chondromata originate in connective tissue, as that of the 
tendons, by a process of cartilaginous metaplasia. Cartilage tumors are 
met with in some of the glandular organs, notably the parotid gland, 
testicle, and ovary; and rarely they occur in the lungs, especially at 
the root and springing from the peribronchial cartilages. 

Ecchondroses are most frequent about the long bones, as those 
of the extremities, and particularly at the epiphyseal attachments, 
where they may reach considerable proportions. Situations of great 
clinical importance are the interpubic and occipitosphenoidal junc- 
tions. In the former situation ecchondroses projecting inward may 
interfere seriously with labor, and in the latter place cartilaginous out- 
growths may penetrate the dura and exercise injurious compression on 
the brain. 

Chondromata proper ma} r occur in the neighborhood of bones, in 
the muscles and tendons near their bony attachments, and in the 
organs mentioned, but in the last situation are rarely pure, myxoma 
being the most frequent associate. 

Structure. — Chondromata resemble hyaline, fibrous, or elastic car- 
tilage, the first named being much the most frequent. The tissue 
differs from normal cartilage in the fact that the cells are frequently 
without capsules and are much less regularly arranged (Fig. 56). The 
intercellular substance is more abundant, and is frequently gelatinous, 
mucoid, or fibrous, and not raiely the different types of cartilage occur 
within narrow limits. Association with myxoma and sarcoma, or both, 
is common, especially in the parotid and testicles, the proportion of the 
several ingredients varying greatly. Calcification and true ossification 
are not infrequent, particularly in cartilage tumors intimately connected 
with bone. The term osteochondroma is applied in such cases. The 
name osteoid chondroma is applied to chondromata in which the inter- 
cellular substance is trabecular in arrangement, suggesting bone structure 
but in which actual ossification has not occurred. Such growths are met 
with about the bones and, as a rule, spring from the periosteum. The 
cartilaginous part of these tumors is without blood-vessels. 

Degenerative changes are frequent because while the tumor as a 



PROGRESSIVE TISSUE CHANGES 



185 



whole is vascular the islands of cartilage are not, and the parts removed 
from the vessels get little nutrition. Myxomatous degeneration may 
occur, though myxoma is more frequent as an association than as a 
degeneration. Softening may occur in the center of the mass, and may 
lead to cyst formation, this being particularly common in the myxo- 
chondromata. Growths of this kind are frequently quite vascular and 
hemorrhages into the cysts may occur. Eventually such cases may show 
scarcely any cartilage cells, a few being perhaps detected in some part of 
the cyst wall. A single hard lump may be left at one side of the cyst, the 
rest of the tumor having softened. 

The more cellular the tumor, the greater the tendency to sarcomatous 
degeneration. Fibrillation and cell increase are early indications of such 
a change. 




Fig. 56. — Chondroma of the hyaline type. 

Nature. — Chondromata are usually benign, and are dangerous only 
through the pressure they exert. Removal of a part of the tumor may 
have a beneficial influence in causing calcification of the remainder. 
Metastasis may undoubtedly occur in pure chondromata through 
transportation of particles in the circulation; such cartilaginous emboli 
have often been demonstrated. The secondary growths are most fre- 
quent in the lungs. Metastatic chondromata are, however, more fre- 
quently chondrosarcomata than pure chondromata. 

OSTEOMA 

Definition.' — An osteoma is a tumor composed of osseous tissue. 
Osteomata are closely allied to cartilaginous tumors, and frequently 
transformations occur. The cell of origin is the osteoblast, as adult 
bone cells do not reproduce. 

Etiology. — The same difficulty is experienced in distinguishing in- 
flammatory outgrowths or exostoses from true bony tumors, as in the 
case of cartilaginous growths. Enlargement of the facial bones in 
leontiasis ossea, of the bones of the extremities in acromegaly and 
hypertrophic pulmonary osteo-arthropathy, and ossification of the 
muscles in myositis ossificans, are instances of border-line conditions 



186 



A TEXT-BOOK OF PATHOLOGY 



separating true tumors from inflammatory hyperostoses. Irritation 
and traumatism undoubtedly play a part in the etiology, even in neo- 
plasms unattached to the bone, and in the case of bony outgrowths 
injury is generally the immediate cause. An underlying predisposition 
undoubtedly exists, and explains the occurrence of congenital multiple 
bony tumors. 




Fie 



■Exostoses of the elbow-joint. 



Appearance. — Two forms may be distinguished, as in the case of 
chondromata: (1) outgrowths or exostoses and osteophytes, and (2) 
the osteomata proper, or heteroplastic osteomata. Exostoses and 
osteophytes are distinguished one from the other by their shape and 
appearance rather than by any essential difference. The former are 
direct outgrowths of more or less wart-like character; the latter are more 
extensive and present the appearance of bony deposits upon bones, and 
are less closely attached (Fig. 57). In both forms the surface of the 

growth is irregular, nodulated, or wart-like 
(Fig. 58). The consistencies that of bone, 
and the size varies from that of small out- 
growths to masses as large as a fist. On 
section, two forms may be distinguished: 
the hard or osteoma durum, after the nature 
of compact bone with fairly well imitated 
architecture; and the soft or osteoma 
spongiosum, after the character of spongy 
bone, but less well arranged, more of the 
embryonic cell type and more apt to show 
degenerative changes. Sometimes the sub- 
stance of the tumor is exceedingly dense, 
and the term osteoma eburnemn is applied. 
This form is without the completed 
Haversian systems, and osteoblasts are apt to be wanting over large 
areas. 

There may be osteomata of endosteal origin arising from endosteum 
or misplaced cartilage. 

The heteroplastic osteomata, or those separated from the bone, are 
more rounded and, when of considerable size, usually nodulated and tab- 
ulated. In the serous membranes they occur as flat bony plates. 




Fig. 58.- — Osteoma of the lower 
jaw (Warren). 



PROGRESSIVE TISSUE CHANGES 



187 



Seats. — Osteomata spring from the bone or cartilage, or from 
connective tissue near the bones. More rarely they arise in other con- 
nective tissues, in the serous membranes, or in certain organs, notably 
the testicle and parotid gland. 

Osteomata connected with bones are most frequent about the 
epiphyses, at the attachments of muscles, or at the seat of old frac- 
tures from which abundant callus has been deposited. The skull 
bones may be affected on the outer or inner surface, and often an ele- 
vation is noted without and within at the same spot. A form of clinical 
importance is that in which exostoses occur on the inner aspect of the 
metatarsal bone of the great toe from compression of tight shoes. In 
the maxillary bones osteomata may originate about the roots of mal- 
formed teeth. In cases of accumulation of cement substance beginning 
at the neck of the tooth the term dental osteoma is applied; these are 
strictly comparable to osteomata. In cases in which proliferation of the 
dental pulp has occurred the term odontoma is applicable, and the 
tumor is not of osseous character. The bony growths sometimes seen 
in the serous surfaces nearly always arise in areas in which there has 
been thickening from chronic inflammation. They are most frequent 
in the dura mater of the brain, particularly the falx cerebri, though the 
membranes of the cord, the pleura, endocardium, or pericardium may 
be involved. 

Structure. — Microscopically, osteomata resemble more or less accu- 
rately bone tissue. They vary, however, in different areas, and mixtures 
of cartilage with bony tissue are frequent. Secondary degenerative 
changes (softening) may occur, and association with tumors of other 
character are not infrequent (chondroma, myxoma, fibroma, sarcoma). 

Nature. — These growths are eminently benign, slow of growth, do 
not recur, and do not give metastasis. Their situation sometimes makes 
them troublesome or dangerous. 

Angiomata 

This name is given to tumors the chief part of which is made up of 
vessels with a relatively small amount of supporting tissue. It is by 
growth of new vessels or increase of tortuosity of those existing that 
these tumors grow. The interstitial tissue may undergo change, but 
the principal feature is vessel sprouting. 1 

LYMPHANGIOMA 

A lymphangioma is a tumor composed of dilated lymph-vessels 
or lymph-spaces, more frequently the latter. It is difficult to separate 
dilatations of lymphatic channels due to obstruction from hyperplastic 
processes. Congenital enlargements of certain parts are met with 
which seem entirely dependent upon the abnormal development of the 
lymph-spaces. These constitute the condition called elephantiasis 
congenita mollis, in which the subcutaneous tissues are boggy or edem- 

1 It is maintained by some that these are not true tumors, as they have no power of 
independent growth and keep pace with the body growth by reason of obstruction or 
an error of tissue resistance. The term "hamartoma " has been applied to them. 



188 



A TEXT-BOOK OF PATHOLOGY 



atous, and even distinct cystic formations occur. Congenital cystic 
hygroma is an instance of dilatation of the lymph-spaces. Congenital 
enlargement of the tongue, termed macroglossia; of the lips, macrochcilia; 
and of the skin, ncevus lymphaticus, are other instances of the same 
process. In all of these, in addition to the dilatation of the lymphatic 
spaces, a marked proliferation of the connective tissues as well as the 
muscle (in the case of the tongue) is striking; but the process, in all 
probability, originates as a dilatation of the lymph-spaces. Beside 
these forms that seem clearly to be malformations or due to inflammatory 
processes, there are local dilatations, which while possessing few of the 
characters of true tumors still show an abnormality of growth placing them 




Fig. 59. — Cystic lymphangioma. 



somewhere in this category. These tumors are sharply outlined, boggy, 
multiloculated masses which on section show cysts of varying size con- 
taining clear or milky fluid; under the microscope fairly distinct connec- 
tive tissue septa separate spaces lined with flat endothelia. If the 
vessels be quite small, the growth is telangiectatic, if large, cystic or 
cavernous. The bursting of dilated lymphatics may lead to lymphorrhea 
or external discharge of lymph when the process involves the skin, or to 
effusions of lymphatic character when the serous cavities are involved. 
Chylous pericarditis, pleuritis, and ascites are thus produced. Rupture 
of dilated lymphatics along the urinary tract (kidney or bladder) occa- 
sions chyluria. Lymphangioma is a benign process in the pathological 
sense. This classification is here limited to those tumors in which vessel 
change is the only feature, growths arising from lining or covering mem- 
branes being placed among the endotheliomata. 



PROGRESSIVE TISSUE CHANGES 



189 



HEMANGIOMA 

Definition. — A hemangioma, or angioma, as it is more frequently 
called, is a tumor-like formation composed principally of blood-vessels. 
Two varieties may be described, that which simulates merely distended 
capillaries and veins {angioma telangiectaticum) , and that in which there 
are enlarged spaces lined with endothelium (angioma cavernosum or 
cavernoma). In many tumors the blood-vessels are somewhat enlarged; 
these are spoken of as telangiectatic tumors. 

Etiology. — -Congenital malformation certainly plays some part 
in some cases, as the frequency of hemangiomata in the newborn and 
particularly at the junction of the branchial arches would indicate. 
Injury, however, and mechanical causes generally also play a part, and 
pre-existing disease, particularly fibroid inflammatory processes, ma}^ 
contribute to the subsequent dilatation and proliferation of the vessels 
(see below). 

Appearance and Seats. — The angioma telangiectaticum may 
consist merely of delicate capillaries and arterioles, and in this case 
a bright red color is observed. The tumor appears as a spot on the 
surface of the skin, more or less sharply outlined from the surrounding- 
tissue. It is not elevated and has the same consistency as the healthy 
parts. Usually it occurs as a multiple condition, and the larger are often 
surrounded by smaller spots. The skin is the favorite seat; but the sub- 
cutaneous adipose tissue and sometimes the mucous membranes are 
involved. Less commonly larger (venous) channels occur in the tumor, 
when a dark red color is observed (port-wine stains). 

If a circumscribed portion of the circulation is uniform^ involved, 
the vessels thicken and elongate, and a peculiar foim of hemangioma 
results. In these cases the arteries are greatly thickened and tortuous, 
and form bunches under the skin, suggesting to palpation a bundle of 
earth-worms, while the surface of the skin presents peculiar irregular ele- 
vations without, of necessity, any change of color (aneurysma racemosum 
seu cirsoideum) . This is not infrequent in the scalp. A similar condi- 
tion of the vessels is observed in the varicosity of the legs, labia, or other 
parts. It is most frequent in the hemorrhoidal veins, constituting the 
ordinary hemorrhoids. (These conditions do not strictly constitute 
tumors and will be more fully described in discussing the diseases of the 
vessels.) 

Cavernous angiomata present themselves as more distinctly tumor- 
like formations of dark venous color, involving the skin or subcutaneous 
tissues, the retrobulbar tissue of the eye, the mucous membranes of the 
nose or pharynx, and certain organs, as the mammae, the kidney, the 
spleen, but particularly the liver. Like the other variety, they may be 
congenital, but more frequently arise in later life, especially that of the 
liver, which is most common in old persons. The appearance is that of 
a more circumscribed tumor, sometimes showing a distinct capsule and 
varying in consistency with the degree of distention of the blood-spaces. 
In the skin it projects slightly from the surface (ncevus prominens). 

Structure. — The definition explains the structure in general. 
The blood-vessels of telangiectatic angiomata may be simply dilated 



190 A TEXT-BOOK OF PATHOLOGY 

capillaries with a lining of endothelium and a fibrous outer coating. 
More commonly the vessels are considerably thickened and held together 
by a reticular connective tissue. In rare instances the vessels are so 
closely packed and the walls so thickened that when the blood is re- 
moved the appearance is not unlike that of the tubules of a sweat-gland. 
The congeries of vessels of a telangiectatic angioma represents the 
elongated and tortuous vessels of the affected area, and also new-formed 
vessels originating from the former. The only connection of the angioma 
with the general circulation is through one or a few afferent arterioles 
and efferent veins. The growth is not merely an enlargement of pre- 
existing vessels, but an actual new formation. 




Fig. 60. — Cavernous angioma (Warren). 



The cavernous angiomata present large spaces lined with endothelial 
cells (Fig. 60). Between these spaces are parallel fibers of connective 
tissue which form the framework of the tumor. In cases involving the 
liver the proper substance of this organ disappears completely, leaving 
only anastomosing spaces with a fibrous framework. Virchow taught 
that the fibrous process was primary, and by traction and pressure 
gradually induced dilatation of the vessels and atrophy of the liver sub- 
stance. Some of the more recent writers believe that the dilatation 
of the vessels is the primary condition. The capsule sometimes found 
surrounding the cavernous angioma is certainly a secondary formation. 

Angiomata of the skin may enclose the hair-follicles and sweat- 
glands; those of the subcutaneous tissue frequently show areas rich in 
fatty tissue (angiolipoma) ; secondary angiomatous change of tumors is 
probably the result of dilatation of the pre-existing or new-formed ves- 
sels. Sometimes secondary change may occur in the connective tissue 



PROGRESSIVE TISSUE CHANGES 



191 



of the vessels of an angioma, as in the plexiform angiosarcomata, in which 
the blood-vessels are surrounded by ensheathing sarcoma-cells (see Fig. 
60). Certain cylindromata have the same origin. 

Nature. — Angioma is essentially benign, and may continue through 
life without enlarging. Hemorrhage and inflammatory or necrotic 
changes are its dangerous consequences. 

LYMPHOMATA 

Tumors of lymphatic tissues form one of the most debated subjects of 
pathology and have been subjected to almost as many classifications as 
there have been writers. This is in part due to the fact that lymph 
nodes and scattered lymph cell collections have been considered sepa- 
rately, in part to our imperfect knowledge of the origin and relation of the 
many types of cells seen in the hyperplasias and in part to the differing 
clinical behaviors of instances of apparently identical pathological proc- 
esses. Lymphatic tissue is made up of lymph cells, connective tissue 
and endothelia, all of which play some part in histological alterations. 
Some authors have claimed that the latter cells can assume the recognized 
characters of lymphocytes while others deny this, asserting the indi- 
viduality of each ; at the present time the latter view seems much more 
probable. In the reaction of lymphatic tissues to infection or irritation, 
all these elements engage and the final product is often similar to what 
has been described as a neoplastic hyperplasia. 

The situation and function of these tissues lay them open to insults of 
all sorts and this is not confined to well defined regional collections, like 
the axillary or inguinal glands, but extends to the lymphoid cell groups in 
the marrow and internal organs. It would seem that often where one 
group is deeply affected, others not only in the vicinity but at remote 
localities respond in some way; whether this is done by metastasis from 
the original focus or by the general effect of the irritant is not known, but 
it is accepted that when marked irritation of considerable lymphatic 
tissue exists, cells may be spilled from the nodes into the circulation. We 
are inclined to think that lymphatic tissues generally feel and respond 
to a marked insult to any one group. Thus it is shown why lymphatic 
overgrowths are so often widespread; strictly localized tumors do occur r 
some that remain entirely in the lymph glands in which they originate, 
simple lymphoma and lymphosarcoma, but lymph node overgrowth is 
more often disseminated than otherwise. Some overgrowths of these 
tissues are accompanied, indeed characterized, by the appearance in the 
circulating blood of an excess of white cells of the mononuclear type. 
Just what determines this is unknown for it occurs in the hyperplasias 
accompanying lymphatic leukemia but not in lymphosarcoma, although 
in certain cases the histology is closely similar. 

The large mononuclear cell of lymphatic organs, and that of bone 
marrow are very closely similar, and play an important figure in the 
cytology of these tumors. Although the genesis and identity are not 
clear, those from the marrow, belonging to the myeloid series show, like 
all myeloid cells, oxidase granules by special stain, while those from 
lymphatic growth centers do not. Special mononuclears, plasma cells, 
have a few distinctive features that have been discussed. 



192 



A TEXT-BOOK OF PATHOLOGY 



With these general remarks we shall pass to a consideration of clearly 
cut forms of lymphatic tissue tumors, in such an order that the readers 
may acquire an idea of types. Certain of them may possibly change to 
another and there are modifications in the clinical course of some that 
simulate others but by study of the history, and the gross and minute 
anatomy, with special stains, the student may fairly well classify a case 
under investigation. • 

Simple lymphoma or lymphadenoma is a tumefaction preserving the 
form and structure of the node and cytologically composed chiefly of 
small cells. These growths appear almost always as the result of chronic 
irritation by bacterial or mechanical agents and differ from chronic 
adenitis in the preponderance of cells over connective tissues. It may be 
that they arise spontaneously, as cases with no discoverable causes are 
recorded but this is rare. They occur as single or grouped firm 
masses in the cervical, axillary, inguinal or other regions, free under the 
skin, which is movable over them unless inflammation bind the two 
together. On section they exhibit a well defined capsule and a firm pale 
yellow or pink appearance. Under the microscope one sees small lym- 
phoid cells in solid masses, the follicles being large and only in early 
stages showing a well marked germ center. Sinuses are filled with the 
same cell. There is no tendency to penetrate the capsule. No charac- 
teristic blood picture is presented. Certain of these cases may be tuber- 
culous, as living attenuated tubercle bacilli have been found by some, 
while others describe structures which they consider remains of these 
organisms. 

Pseudoleukemia was described by Cohnheim as a more or less gen- 
eralized lymphatic hyperplasia without increase of circulating lympho- 
cytes. It is generally considered the same as Hodgkin's disease but 
occasionally one sees cases of generalized nodal enlargement without 
fibrosis, eosinophiles or multinuclears, and without leukemic blood. 

Lymphosarcoma while possibly considered appropriately under the 
heading of sarcomata, is the next grade of hyperplasia of these organs in 
which the original cell forms are retained, and which has no special blood 
picture. There are two cells in these tissues from which sarcoma may 
emanate, lymphatic mononuclears and reticulum cells. The latter we 
shall dismiss for the present by stating that it resembles the usual type of 
this tumor, seems to be more commonly of the large cell type, and gives 
metastasis readily. Lymphosarcoma or lymphoblastoma (Ribbert) 
strictly speaking, occurs chiefly in the third and fourth decades of life and 
has followed typhoid and tuberculous hyperplasias frequently enough for 
some authors to ascribe to these conditions an etiological role. It does 
not seem to us that there is in the behavior of the growth any necessity 
of separating it from tumors for it is an invasive process occa- 
sionally sending out metastasis. It occurs especially in gland groups or 
in the intestinal wall, forming soft, pale yellow or pinkish masses which 
spread by leaving the normal confines and infiltrating adjacent muscles or 
organs. In the thorax it may extend to the lungs or through the heart 
wall to its chambers. In the intestinal tract the growth appears as thick- 
enings of the wall which behave in two ways. In the first form there are 
internal swellings and foldings of the mucosa which may narrow the 



PROGRESSIVE TISSUE CHANGES 



193 



lumen. In the other the growth seems to penetrate the submucosa and 
muscularis so that the tone of the wall is lost and dilatation results. In 
both cases there is a diffuse thickening of pale yellow or pinkish color. 
The histology of these tumors embraces two sizes of the lymph cell, which 
are considered by some to be types of the growth, by others as phases of 
development of the same element. As there are inadequate data to show 
that the two sizes behave any differently, they may be considered as 
representing the same tumor. The cells are the usual lymphocytes, 
varying a little in the amount of protoplasm and density of the nucleus. 
The diagnosis of this tumor, as distinguished from the leukemias, is prac- 
tically impossible from microscopical study alone, one being obliged to 
know the history and blood picture of the case. The increase of circulating 
mononuclears is not so great as in leukemia,, not characteristic in differ- 
ential count and may be entirely lacking. Metastasis is not uncommon, 
occurring chiefly by extension along lymphatics but hematogenous 
dissemination is known. That form which embraces a large amount of 
tissue locally and spreads to adjacent organs is known as lymphosar- 
comatosis. The outcome is usually fatal but cures by operation are 
recorded. 

Hodgkin's disease, lymphogranuloma, or granuloma malignum, is an 
atypical hyperplasia of local and generalized distribution with very in- 
definite if any peculiar blood picture. The disease occurs chiefly in 
adults or the adolescent and begins as regional gland swellings with the 
units remaining separate until late in the disease or when secondarily 
infected. The disease usually begins as a swelling of some group of 
regional glands which continue to grow to disfiguring proportions, often 
leading to obstruction of lymphatic and venous drainage so that local 
edema occurs. While the original focus may be local, it is usually fol- 
lowed in a short time by spread to other nearby glands or it leads to 
hyperplasia of lymphoid collections in the internal organs; how this may 
be brought about we have already discussed. The glandular growths 
remain composed of groups of glands that can be shelled out or pulled 
apart; the lesions within organs are partly circumscribed. The spleen 
may be affected by a general hyperplasia or beset with small sharply 
outlined nodules of the characteristic histology. There are forms of this 
disease in which the spleen, the intestinal wall, the abdominal gland or the 
skin show the most striking lesions but since the histology and course are 
much the same and since they may be all combined in some given case, 
there seems to be no reason to separate them. The effect of the localized 
tumefactions depends upon their localization and size, the distortion and 
pressure destroying or invalidating adjacent parts. In one case seen by 
us there was a mass the thickness of a man's forearm extending from the 
right cervical region through the opening of the thorax, down the pos- 
terior mediastinum and ending in a large mass involving the spleen and 
left lobe of the liver, which compressed the esophagus to a slit, caused 
constriction and ulceration of the trachea, pushed the heart to the right 
and collapsed the left lung, while the stomach was entirely below the 
umbilicus. There is beside the effects of pressure, a moderate grade of 
cachexia, a chlorotic anemia, and some white cell increase may be occa- 
sionally found; an increase of eosinophiles and the appearance of mast 

13 



194 



A TEXT-BOOK OF PATHOLOGY 



cells are reported by some but we cannot ascribe to them a high diagnostic 
value. The cause of this disease is not known but perhaps the majority 
of observers credit or stoutly maintain that it is a form of tuberculosis of 
lymph glands and Ewing says that whatever the cause be, it follows 
tuberculosis like a shadow. Ever since Reed clarified our knowledge of 
the subject by a succinct presentation of its anatomy and histology, 
observers report the finding of atypical tubercle bacilli or what they 
believe to be their remains. Tuberculous lymph tissue, that is with 




Fig. 61. — High power detail of the histology of Hodgkin's disease, showing particularly 
the large mononuclears. The large contrasting cells are probably the endothelioid cells, 
while the paler ones are probably fibroblastic elements. 

frank bacteriological findings, gives at times a picture of endothelioid 
cell increase like Hodgkin's. All that one can say today is that the cause 
is unknown and that tubercle bacilli are found with great difficulty if at 
all in the diseased tissue. Other observers have found what seems to be a 
diptheroid organism and have used it in a vaccine or in the production 
. of an antiserum from which means they think to have obtained clinical 
results. Whether the process be infectious or neoplastic is not yet 
settled but the progress of histological change leads one to consider the 
former as more probable. 



PROGRESSIVE TISSUE CHANGES 



195 




Fig. 62. — Myeloma focus in liver-fatty degeneration of adjacent liver cells. 




Fig. 63. — High power picture of myeloma of the plasma-cell variety, associated with 
Bence-Jones albumosuria and osteoporosis. 



196 



A TEXT-BOOK OF PATHOLOGY 



Grossly, the lesions of Hodgkin's disease are firm well outlined masses 
which on section are smooth white or yellow or yellowish brown. The 
capsule is not invaded but one may at times see extensions along fascial 
planes or around-blood vessels. Microscopically the process begins as an 
increase of reticulum and endothelial cells, the lymphocytes taking little 
part, as a rule, and disappearing entirely from some fields. In a few cases 
seen by the authors they have been quite numerous but this did not con- 
ceal the characteristic picture. The essential cells, reticular and endo- 
thelial, swell to large forms with loose cytoplasm and a vesicular, oval or 
polymorphous nucleus. Some of these especially with oval nuclei seem 
directly derived from the connective tissue and are probably engaged 
in later new connective tissue formation. The other large cells, probably 
endothelial in origin, grow to great size, possess palely staining poorly out- 
lined cytoplasm and . are supplied with oval, bean-shaped or bilobed 
nuclei; certain of them have more than one nucleus. Multinucleated 
cells are indeed fairly characteristic of malignant granuloma particularly 
when the nuclei are arranged in a ring about the periphery leaving a space 
of protoplasm in the middle; the nuclei are disposed parallel to the cell 
wall and not radially as in the Langhans' giant cell. 

The original hyperplasia of these cells causes disappearance of the 
glandular arrangement for they occupy both chords and sinuses and even 
form distinct nodules. Eosinophiles are quite common, scattered irregu- 
larly through the tissues and their discovery assists one in diagnosis; they 
are, however, not essential to the process and their exact importance is not 
understood. Polynuclear leukocytes are present in varying numbers, 
but there is nothing peculiar about their presence or distribution. 

While the large cells are forming, fibroblastic processes are in action 
and lead to a separation and constriction of the above discussed cells of 
large size; possibly this is the causation of cells with ringed nuclei, they 
having aiisen from giant cells pressed by connective tissue. The fibrous 
new growth continues until large strands of this nature are seen running 
through the section. It is interesting and noteworthy that in the earliest 
stages the fibrous reticulum is very delicate and almost invisible while the 
last stage is marked by exceedingly dense and constricting fibers. 

The lesions in the internal organs are closely similar to those just 
described, but perhaps more cellular as they can spread along tissue 
spaces and about blood-vessels with greater ease than in lymph nodes; 
this probably accounts for less fibrosis in them. The bone marrow may 
show localized granulomatous nodules. With this disease at times one 
notes a slightly pigmented patchy thickening of the skin and the under- 
lying lesion to this seems to be a more or less diffuse granulomatous 
infiltration. The course of Hodgkin's disease, untreated, seems invari- 
ably to be to a fatal end. Careful persistent treatment by experienced 
clinicians has been in many cases rewarded by marked improvement if the 
case has been seen early. X-ray can be used with good result in certain 
cases; it is of no avail in a second group, while a third class seems to be 
unfavorably influenced by it. 

The leukemias emanating from the hj^perplasias of lymphatic tissue 
are usually associated with some form of tumefaction. The two forms of 
the disease, acute and chronic, are somewhat similar in their strict pa- 



PROGRESSIVE TISSUE CHANGES 



197 



thology with due account for the difference in duration and the evident 
vigor of the causative agent whatever it be. This is the principal tumor, 
if tumor it be, of the lymphatic tissue that, is associated with increased 
circulating mononuclears. We shall not discuss it here beyond a brief 
description of the lymph node changes, leaving the subject for full dis- 
cussion among diseases of the blood. The hyperplasias in lymphatic 
leukemia are generalized, apparently limited to lymphatic tissues and 
the cellular changes are homogenous and homologous in all lesions. In 
the acute form the swellings are moderate or slight, consisting of soft, 
moist, pinkish or yellowish masses confined by the capsule of the gland, or 
in organs as areas illy defined against the visceral substance. Hemor- 
rhage, being common in this acute disease, may modify the picture. 
Microscopically the lymphatic collections are in a great state of activ- 
ity but withal there is a tendency to retain the topography of the tissue. 
In chronic leukemia the glands are usually definitely enlarged over the 
whole body, are firmer and drier than in the acute form, gray white 
and tend to remain separate. The smaller lymphatic collections are also 
greatly exaggerated and white or yellow tumors are seen in the organs. 
Under the microscope one sees an enormous overgrowth of small lymph 
cells which has destroyed nodal architecture but does not leave its 
boundaries. 

There might be also mentioned a form of these tumors called leuco- 
sarcoma, having a histology like the leukemias, but not so homogeneous, 
and giving rise to localized tumors, occasionally spilling out some mono- 
nuclears into the blood. The difference between it and leukemia is that 
the latter always gives an increase of mononuclears in the blood and is 
generalized, while the former only occasionally cause mononuclear in- 
crease and is localized. 

Multiple Myeloma. — This growth affects the sternum, ribs, vertebras, 
skull, and, less frequently, other bones. The tumor at first suggests a 
hyperplastic condition of the marrow; later the substance of the bone is 
replaced by the growth, which may finally break through the shell of 
bone covering it and invade the soft tissues. Metastasis is very rare. 
The growth has a mottled grayish and reddish appearance and is rather 
soft. Microscopically it is composed of round cells and a vascular 
network of thin-walled vessels. (See Bone Marrow.) 

Chloroma is a term covering destructive greenish tumors of bone 
marrow affecting chiefly young males and practically always fatal in 
outcome. The color is variously ascribed to an obscure lipochrome and to 
the abundance of eosinophiles; it vanishes after short exposure to the air; 
heart clots after death may be tinted green. The cranial bones are 
chiefly affected but any other may be attacked. The process is decidedly 
infiltrative and destroys adjacent muscles and organs. Perhaps its most 
characteristic gross feature, after the color, is its power to penetrate the 
shaft or plate of bones and grow as an irregular mass under the perios- 
teum. Two forms have been distinguished, the lymphoid and the 
myeloid. The former consists of masses of large pale nongranular cells 
while the strict myelogenous elements are conspicuously few in number. 
This form gives metastasis to lymph nodes and allows the mononuclears 
to overflow into the blood stream. The myeloid variety shows large 



198 



A TEXT-BOOK OF PATHOLOGY 



cells of the myeloblasts series including promyelocytes, myelocytes and 
polynuclears; marrow in other bones may be similarly affected. In this 
form visceral metastasis may occur and a leucocytosis of the myeloid 
type appear. Thus it will be seen from the foregoing that this process is 
like tumorous leukemic one, but indeed there is much debate as to 
its exact nature. 

SARCOMA 

Definition. — The term " sarcoma" is applied to tumors composed 
of connective-tissue cells with very little intercellular substance. It 
is often said that sarcoma-cells resemble those of embryonal connective 
tissue; properly speaking, they may be likened to the ordinary con- 
nective-tissue cell falling short of complete development — that is, no 
formation of fibrous intercellular substance, but a great tendency to 
continuous cell proliferation. 

Etiology. — Of all the tumors, sarcoma furnishes the best ground for 
Cohnheim's theory. Its frequent occurrence in young persons, the 
relation of melanosarcomata to congenital pigment-spots of the skin, 
and the sarcomatous mixed tumors of the parotid and testis were cited 
by Cohnheim among the evidences pointing to a congenital origin. 
Traumatism and inflammation certainly play some part, either in stimu- 
lating sudden growth of a latent sarcoma or in developing a lesion from 
which sarcoma springs. The parasitic theory has gained many adher- 
ents in recent years, though no specific organism has been demonstrated. 
Experiments at implantation of the disease in animals have been par- 
tially successful, but do not establish an infectious character, as has been 
shown in preceding pages. It is not improbable that certain lympho- 
sarcomata may be due to the action of bacteria. 

Appearances. — Sarcomata are generally more or less rounded 
tumors, often enclosed by a limiting reactive inflammation of the neigh- 
boring tissues; they may, however, be irregular, infiltrating, and, 
therefore, unencapsulated. The growth of sarcomata is from the tumor 
cells themselves. The tumor spreads into the surrounding tissue and 
absorbs it, probably only retaining such connective tissue as it requires. 
A true fibrous capsule, made by the tumor and within which it 
grows, does not occur in sarcomata. Some forms appear on surfaces, 
spreading as flat elevations more or less irregular in outline. The 
consistency is soft or hard according to the number of cells and the 
amount of intercellular substance, or according to the kind and amount 
of associated tissue (myxomatous, chondromatous) . Typical sarcoma, 
as the name implies (aapl-, flesh), is flesh-like in consistency, and 
frequently, on section, the color is pink or of a flesh-tint. Many of the 
sarcomata, however, are quite white or gray, and a whitish liquid 
exudes from the surface on section. 

Dilatation of the blood-vessels may cause a decidedly hemorrhagic 
appearance, and actual hemorrhages may take place, causing blood- 
cysts or, subsequently, serous cysts. Other degenerative changes, 
such as necrosis, mucoid change, and simple liquefaction necrosis, may 
render sarcomata soft and often cystic. Sarcomata of glandular organs 



PROGRESSIVE TISSUE CHANGES 



199 



like the breast may present a cystic appearance in consequence of 
compression, and subsequent dilatation of the glandular ducts and acini. 

Angiosarcomata (the variety in which sarcoma-cells spring from 
the adventitia of blood-vessels) present themselves as more or less 
irregular growths, frequently flattened and branching when the surfaces 
of organs are involved. 

Secondary sarcomata are nodular in character and nearly always 
present a capsule if the size is at all considerable (Fig. 64). They are 
usually white or pinkish, rather firm on section, but with a tendency to 
central necrosis or softening. In some cases almost every part of the 
body may be studded with 
minute white spots scarcely 
distinguishable from miliary 
tubercles. This condition is 
called sarcomatosis. 

Seats. — Sarcomata spring 
from pre-existing connective 
tissues such as the subcutaneous, 
intermuscular, periosteal, or ten- 
dinous tissues; bone, cartilage, 
fat, lymphatic glands, the sub- 
mucous and serous surfaces. 
They may arise in the internal 
organs; kidney, liver, spleen, 
thyroid glands, testis. The in- 
dividual seats will be further 
considered under the different 
forms. 

Structure. — The sarcoma- 
cell is rounded, cylindrical, 
spindle shaped, or of polymor- 
phous forms, the last usually 
being larger than the the round 
or spindle forms. The large 
number of cells in comparison 
with the amount of intercellular 
substance is always conspicuous. 
The cells themselves contain 

rather large nuclei of a somewhat vesicular appearance, though some- 
times quite granular and hyperchromatic. In rapidly growing- 
tumors karyokinetic figures may be very abundant; less frequently 
the cells show evidence of direct division of the nuclei. Nuclear 
degenerations (karyorrhexis, karyolysis, and hj^perchromatosis) are 
frequent, and doubtless cause some of the appearances sup- 
posed to be protozoa. The arrangement of the cells in sarcomata 
is usually very irregular; in some cases, however, particularly in 
spindle-celled sarcomata, the cells lie in fasciculi or parallel columns. 
These are the alveolar sarcomata. The intercellular substance consists 
of a homogeneous matrix with a few fibers in the case of the spindle- 
celled variety, but with few if any in other cases. The cells may be 




Fig. 64. — Secondary sarcomata of the lung: 
the primary growth was attached to the 
pleura. 



200 



A TEXT-BOOK OF PATHOLOGY 



all of one type, but more frequently different forms or shapes occur in 
the same tumor. Among the polymorphous forms of cells may be noted 
large flattened cells resembling endothelial plates and giant-cells resem- 
bling myeloplaques. (These forms will be discussed under the headings 
Endothelioma and Giant-celled Sarcoma.) 

When grown in serum outside the body, sarcoma cells at first multi- 
ply more rapidly than normal ones, but soon lose this power. Irregular 
mitoses are seen, but direct division is not. 




Fig. 65. — Round cell sarcoma, of mixed sizes of cells. This is a common variety in the 

genital organs. 

The blood-vessels of sarcoma are usually channels lined with a single 
endothelial coat (see Fig. 68), but there may be more fully developed 
vessels. There is growth of these imperfectly formed vessels, following, 
in general, the laws of new capillary development. In some cases the 
vascular network is very conspicuous and forms the skeleton of the 
tumor, the sarcoma-cells being ranged round the vessels in the form of 
mantles and probably springing from the adventitia. In spreading, 
sarcoma shows a tendency to follow vessels. It has no lymphatics and 
only such nerves as it encloses in its growth. Secondary changes may 
occur in the cellular masses surrounding the vessels, and peculiar forms 
of tumors thus result. (See Cylindroma;) 

The general architecture of a sarcoma has decided influence upon 
its character. The round-cell tumors are usually of rapid growth and 
the small round-cell type of the greatest malignancy among the simple 
sarcomata. The soft loose-textured ones are usually most malignant. 



PROGRESSIVE TISSUE CHANGES 



201 



Combinations of sarcoma with other forms of tumors are not rare. 
All grades between the true sarcoma and the fibroma may be met with, 
and it is difficult to draw a line of distinction. Wherever a tendency to 
cellular proliferation is conspicuous and the formation of fibroblastic 
cells with elongated fibrous projections is not conspicuous, it is warranted 
to record the tumor as sarcomatous. Primary fibromata may become 
sarcomatous, and sarcomatous tumors perhaps at times become more 
benign by fibromatous transformation. Combinations with chondroma, 
osteoma, myxoma, and other connective-tissue tumors; with adenomal 
rhabdomyoma, and fibromyoma are not infrequent. More rarely 
the fibrous tissue of the benign tumors may undergo sarcomatous change. 

The structure of individual forms of sarcoma will be separately 
considered. Names have been applied to the different forms which 
describe the micro-anatomy, and in a sense are instructive in suggesting 
the relative activity and possible nature of the growth. It must not 
be forgotten, however, that round- and spindle-cell sarcomata both de- 
scend from the same parent cell and may be phases of differentiation. 

Nature. — Sarcoma is essentially malignant. It tends to recur 
after removal; it affects the general health of the patient, and metastasis 
is frequent. Metastasis occurs through the circulation chiefly, but 
may spread through the lymphatics. The degree of malignancy varies 
greatly. The small round-celled and melanotic varieties are the most 
dangerous. Some forms, as the giant-celled and the fibrosarcomata, are 
comparatively benign. The relatively benign form of tumor, called 
recurrent fibroid tumor by Paget is, in reality, a fibrosarcoma. The 
growth of sarcomata is usually rather rapid, but shows a tendency to 
irregularity, and may become very rapid in consequence of irritation. 

Sarcomata are injurious to the general health in some obscure way. 
The evidence of this is the anemia and leukocytosis and the irregular 
fever observed in various cases. The anemia may be trivial or severe, 
and may become extreme. Leukocytosis is frequent, but rarely marked. 
The polymorphous elements may be specially increased, but we have 
found the lymphocytes excessive in a number of cases. Irregular fever 
is often noted in lymphosarcoma and sarcomatosis. Necrotic change 
may increase the tendency to fever. The exact influence of sarcoma on 
metabolism in unknown. 

We feel that we should not leave the general subject of sarcoma with- 
out a word of caution concerning its diagnosis. There are cases of round 
cell infiltration around old bone, joint and gland lesions and there is such 
a thing as chronic granulation tissue with the persistence of closely packed 
large fibrous tissue nuclei, both of which have a considerable resemblance 
to certain sarcomata. Close attention should be given to cellular 
arrangement and the size and wall of blood vessels, while the pathologist 
should have either the gross specimen or see the operation; the history of 
the case should always be at his disposal. 

Spindle-cell Sarcoma 

This form may consist of either large or small spindle-shaped cells 
with attenuated and sometimes branching extremities, and a spindle- 



202 



A TEXT-BOOK OF PATHOLOGY 



shaped nucleus in the small cell variety, while the large cells have an 
oval, bladder-like nucleus (Fig. 67). Angular or stellate cells are not 
infrequent. The cells may be ranged in parallel columns, so that the 
tissue becomes quite compact; and fasciculi of such cell masses may run 
in different directions, interlacing, and thus giving the section a fibrous 
appearance. In some cases the cells present no definite arrangement. 
Spindle-celled sarcomata are harder than the round-celled varieties 
and usually more grayish or flesh colored. They may be quite soft and 
white or degenerated and cystic. 



The amount of intercellular substance in some cases, particularly of 
the small cell type, is quite considerable, and the term " fibrosarcoma' ' 
may be justified. The intercellular fibrils are of the fibroglia type and 
are indistinguishable from those of fibromata. It is very difficult some- 
times to decide whether the tumor is sarcomatous or purely fibromatous. 
The large cell type is more cellular. 

Spindle-cell sarcomata occur in the dense connective tissue of the 
periosteum, tendons, and fasciae; less frequently, in the softer tissues. 
They are slow of growth, relatively benign, some cases showing no tend- 
ency to metastasis, though recurring after removal. 

When studying sections from such tumors, the observer will note 
areas in which the cells seem small and round; these are strands cut 




Fig. 66. — Spindle cell sarcoma. 



Fig. 67. — Cells from a large spindle- 
celled sarcoma. 



PKOGRESSIVE TISSUE CHANGES 



203 



transversely. Mixed forms of large and small spindle cells are occasion- 
ally seen and combinations with true round cells are reported. 

Round-cell Sarcoma 

Sarcomata may be composed almost entirely of spherical or round 
cells, small or large in size. The designations " small" and "large round- 
celled sarcomata" are used, but do not really define separate varieties, 
The round cells when small resemble those of lymphatic organs. There 
is little intercellular substance. The blood-vessels may be quite large 




Fig. 68. — Small round-cell sarcoma; in the center is seen a blood-vessel with its wall 

of endothelium. 

and hemorrhages with secondary changes may occur (Fig. 68). The 
larger cells contain relatively more protoplasm, frequently several nuclei, 
a clear nucleolus, and not rarely different forms of cells (spindle shaped 
and polymorphous) are associated. 

These tumors appear as single fairly well outlined white or gray masses 
in fascias or even in organs. 




Fig. 69. — Lymphosarcoma of nasal mucous membrane: a, on left side a blood-vessel, 
on right side reticulum; b, cells of reticulum; c, sarcoma-cells (Ziegler). 

The naked-eye appearances of round-celled sarcomata are usually 
quite characteristic. They are milky- white, gray, or pink in color; 
sometimes quite soft or cheesy in the center, and a milky liquid exudes. 
Cystic changes and even calcification may occur in the center. When 
central degeneration occurs the cells near the blood vessels remain intact 
giving the impression they grow from the vessel or around it and they can 
be confused with angiosarcoma. Some would explain the latter always 
on this basis but as we shall see later there are certain tumors the struc- 



204 



A TEXT-BOOK OF PATHOLOGY 



ture of which can scarcely have the genesis just suggested and seem to be 
quite separate from the round cell sarcomata. 

The small-cell variety is, as a rule, softer than the larger, though 
both are soft. Round-celled sarcomata are always malignant, the small- 
celled form being perhaps the most malignant of all varieties. 

Lymphosarcoma is a variety of round-celled sarcoma. The ap- 
pearance is the same as that of the other forms, but, microscopically, 
a close resemblance of structure with that seen in lymphatic glands is 
discovered. The principal characteristic is the reticulum or stroma 
formed by branching stellate cells united by their prolongations. In 
the meshes of this reticulum lie lymphoid round cells (Fig. 69). The 
stroma may not be plainly visible unless sections are shaken to dislodge 




Fig. 70. — Round cell sarcoma, with alveoli separated by delicate septa. 



the cells from the reticulum. The lymphosarcoma cell has a rather 
large round eccentric nucleus surrounded by a basophilic granular 
protoplasm. The distinctions of lymphosarcoma from lymphadenoma 
have been discussed under the latter heading. The principal feature of 
differentiation is the tendency of lymphosarcomata to extend beyond 
the normal limitations of the gland or other structures in which they 
originate, whereas lymphadenomata are confined by the glandular 
capsule. 

Alveolar sarcoma is a sub variety of round-celled sarcoma, though 
there are always spindle cells as well. It is distinguished by the occur- 
rence of structures suggesting acini and filled with large round cells 
having a more or less decided epithelioid appearance. The stroma 
forming the acini is composed largely of spindle-shaped cells with a 



PROGRESSIVE TISSUE CHANGES 



205 



certain amount of fibrillar intercellular substance (Fig. 70). The blood- 
vessels supplying the tumors traverse these trabecule. The round cells 
within the alveoli may vary greatly in size, though they are usually 
large. The macroscopical appearance is not specially distinctive; many 
of the cases, however, are pigmented (see below). Alveolar sarcoma is 
most frequent in the skin, where is springs from moles and warts. It 
may also occur in the lymphatic glands, the serous membranes, and 
other parts. It has occasionally a strong resemblance to carcinoma at 
which times a diagnosis can be reached by consulting the history, the 
distribution of the tumor and by staining for fibrils which will be foimed 
between sarcoma cells and not in the nests of carcinoma. 

In some cases the alveolar appearance of the sarcoma is due to the 
fact that the sarcomatous proliferation has occurred in the adventitia 
of blood-vessels, forming a plexus. In this way the meshes of the vascu- 
lar plexus become filled with round cells and the alveolar appearance 
results. In other cases the alveolar character is due to the occurrence 
of sarcomatous foci of circumscribed character in a connective tissue. 
These in their growth push the connective-tissue elements aside and 
thus form alveolar structures. 




Fig. 71. — Giant-cell sarcoma (Warren). 



Giant-cell Sarcoma 

This variety is characterized by the presence of large multinuclear 
cells resembling exactly the myeloplaques of bone. The remaining 
portions of the tumor may be spindle celled or round celled; perhaps 
more frequently round and spindle cells are associated. The giant- 
cells are often exceedingly large and contain several or many nuclei in 
the center of the cell (Fig. 71). The formation of these cells is most 
likely due to rapid nuclear multiplication. In some cases they would 
seem to be caused by obliteration and transformation of capillary 
blood-vessels; but the theory that they result from a fusion of cells 



206 



A TEXT-BOOK OF PATHOLOGY 



seems unwarranted. Ziegler and others maintain that the presence 
of giant-cells does not form an essential characteristic of a peculiar 
type of tumor, but that it is accidental, resulting from continued irri- 
tation. The occurrence of giant-cells in sarcomata of bones would then 
be explained by the constant irritation of the bony particles, while in 
other cases the presence of masses of blood-pigment in the sarcoma ac- 
counts for the development of giant-cells in the vicinity. This view is 
supported by considerable authority and seems reasonable. 

Giant-cell sarcomata occur most frequently about bone, and the 
terms osteosarcoma (a term to be avoided for this growth) and myeloid 
sarcoma have been given in consequence. They may, however, occur 
in other situations. Their nature is usually benign, metastasis being rare. 



may be giant-cells, but they do not dominate the field as in the 
tumor just described. There may be several kinds of cells in the 
osteosarcoma. Such tumors are definitely progressive and malignant, 
as against the less active giant-cell myeloid tumor above. With their 
growth they absorb bony tissue, and lay down new atypical osseoid 
material. They may be cartilaginous, or chondro-osteosarcomatous, or 
any combination of bone, cartilage, and sarcoma. The various kinds 
of cells found in sections of this tumor indicate alterations in cells 
natural to bone, either taking part in the sarcoma or being modified 
by the new growth. Thus one may find cells resembling adult bone 
or cartilage cells and sarcoma-cells. When growing within a bone 
these tumors thin the shaft so that the thinned-out bone gives the 
"egg-shell crackle." There is produced an irregular enlargement of the 




They do have the power however 
to penetrate the shaft of the bone. 
Their appearance in the split bone 
is that of a mushy red formless 
mass. 



The giant-cell sarcoma of bone 
is usually rather slow in growth, 
and gives rise to hard and irregular 
tumors, firmly attached to the 
bony structures. It may begin 
within the bone as a myelogenous 
form (Fig. 72) or from the perios- 
teum. Secondary myxomatous or 
other change may cause more or 
less softening. The bone most 
frequently involved is the maxilla, 
the tumor known as epulis (sar- 
coma springing from the gums 
or alveolar processes) being gen- 
erally a giant-celled sarcoma. 



Fig. 72. — Myelogenous osteosarcoma of the 
tibia (modified from Kast and Rumpel). 



The true osteosarcoma is a more 
definitely neoplastic process in- 
volving a growth of young, ir- 
regular connective-tissue cells with 
imperfect bone formation. There 



PROGRESSIVE TISSUE CHANGES 



207 



whole bone, and by the abnormally laid down osteoid tissue together with 
absorption of the normal bone the, shaft is destroyed. The periosteal 
sarcomata tend more to retain the shaft plate and grow as an irregular 
mass about the bone; however, even this form may destroy the whole 
shaft when it is very cellular and rapidly growing. The more cellular 
and less bony, the more malig- 
nant are these tumors, and vice 
versa (Fig. 72). 

Melanosarcoma 

Melanosarcoma, melanoma, 
chromatophoroma, or pigmented 
sarcoma is a form in which the 
tumor presents a dark color on 
account of the presence of black 
or brown pigment. The latter, 
according to careful chemical 
studies of Berdez and Nencki, 
contains no iron, and is, there- 
fore, not a simple blood-pigment, 
but melanin, a product of cell 
metabolism. Iron-containing 
pigment has been found in some 
tumors, and sometimes in true 
melanosarcomata, being found 
outside the cells and probably 
accidental, the result of hemor- 
rhagic extravasations. The true 
melanin pigmentation occurs in 
the cells, in the cellular pro- 
longations, or the intercellular 
fibrils. It is most frequently 
present in the form of brownish- 
black granular matter, or may 
occur as a diffuse stain. 

Melanosarcoma most com- 
monly arises in the skin, esp- 
ecially in pigmented moles or warts, in the choroid coat of the eye, or in the 
pia mater. The growth is found to consist of cells of various shapes, some- 
times round or irregular, sometimes spindle shaped, but there is a very 
constant tendency, especially in the pigmented sarcomata of the skin 
springing from warts, to assume an alveolar arrangement. In these, 
the cells around the periphery of the alveoli are more or less spindle 
shaped, while those in the center are large, irregular, or rounded cells, 
sometimes epithelium-like. Melanotic sarcomata of the choroid are 
composed very largely of cells having an elongated character with 
drawn out extremities. These resemble the normal pigment cells of 
the choroid coat. 

Melanosarcoma is extremely malignant, recurring when removed and 
frequently causing extensive metastasis (Fig. 74). The latter involves 




Fig. 73. 



Bony structure of osteosarcoma of 
tibia. 



208 



A TEXT-BOOK OF PATHOLOGY 



the local lymphatic glands in the first place, but later various organs, 
especially the liver. The metastases may be of the same structure as 
the original growth, but sometimes non-pigmented metastatic growths 
occur in association with the pigmented ones. Occasionally the sec- 
ondary deposits are more pigmented than the primary growths. The 
melanoma originates from the pigment-containing cells or chromato- 
phores of the part in which they originate. In the skin these are found 
in close association with the lower layers of the epidermis, and 

some authors have insisted that they 
are essentially epithelial in origin and 
that the tumors should, therefore, be 
considered as carcinomata. There 
is, however, considerable ground for 
believing that the chromatophores 
are invariably connective-tissue cells. 
Melanosarcoma is a definite growth 
and not merely a sarcoma that hap- 
pens to be pigmented. 

Mycosis Fungoides 

Mycosis fungoides or granuloma 
fungoides is a pathological condition 
of the skin and subdermal structures, 
having certain resemblances to sar- 
coma and to some of the infectious 
inflammations. 

Etiology. — Very little is known 
regarding the causes of this disease. 
Various bacteria, principally micro- 
Fig. 74. — Metastatic melanosarcoma cocci, have been discovered in the 
of lung showing pigmented and non- i es ions, but none of these has been 

pigmented nodules (Irom a specimen m , , , , , . , „ , 

the possession of Dr. Allen J. Smith). shown to be pathogenic. A lew ob- 
servers have found bodies resembling 
protozoa; but it is not certain that these were really animal organisms. 

Appearance. — The disease frequently presents distinct stages. 
First, the skin becomes somewhat swollen and red and presents eczema- 
tous lesions. In some cases the appearance is that of an erysipelatous 
inflammation. In the next stage nodular elevations occur, and finally 
tumors of considerable size, sometimes as large as an orange, and more 
or less fungoid in appearance. Necrosis is frequent and watery or bloody 
liquid is discharged. The tumors may have an angry, red appearance, 
and have been likened to tomatoes. Rapid disappearance and reappear- 
ance of the tumors is a peculair feature. 

Any part of the body may be affected, and usually the lesions are 
multiple. 

Structure. — Microscopically, the structure of the tumors is allied to 
that of lymphadenomata. There is a proliferation of connective-tissue 
cells about the blood-vessels and glands at the base of the papillse of the 
skin, forming a network or reticulum in which round (lymphoid) cells 
are embedded. The cells, however, may be irregular in form and size. 




I 

PLATE 2 




Melanosarcoma. 



PROGRESSIVE TISSUE CHANGES 



209 



Mitotic figures may be found. Early in the disease the new-formed cells 
degenerate considerably, but later proliferation predominates, and the 
tumor results. The epithelium covering the growth may be thinned 
to a single layer, or it may show thickening. In the latter case enlarged 
papillae dip down into the round-cell collections and the sections have 
somewhat the appearance of carcinoma. Epithelioid cells and giant- 
cells may occur. The tumors are poorly supplied with blood-vessels, 
and to this is attributed the tendency to central necrosis. Inflammatory 
infiltration (polymorphous leukocytes) is not observed to any consider- 
able degree, excepting in the latter stages around and in the areas of 
necrosis. Mast-cells are often abundant. 

Associated Conditions. — In some cases enlargement of the lym- 
phatic glands, liver, and spleen has been observed, and has suggested 
the term pseudoleukemia cutis. Occasionally the blood presents leukemic 
characters. 

Nature. — The disease presents many resemblances to sarcoma or 
lymphadenoma, and it has frequently been described as multiple sarcoma 
of the skin. In other respects it is allied to the infectious inflammations, 
though there is much less evidence of true inflammatory infiltration 
than in these. The relationship to leukemia and pseudoleukemia is 
unsettled. 



Angiosarcoma 

The angiosarcomata are growths depending upon a proliferation of 
endothelium and an expression of the tendency of these cells to make new 
vessels. The tumors arising in lymph-channels are called lymphangio- 
endothelioma or lymphangioma, while those in blood-vessels are called 
hemangio-endothelioma, or simply angiosarcoma. In the second variety 
the sarcomatous proliferation may begin in the adventitious coat of 
blood-vessels {perithelioma). 

Angiosarcomata are met with in the serous membranes, in the skin, 
and especially in the salivary glands. Very rarefy they occur in other 
parts of the body. The tumor is, as a .rule, quite vascular, but may not be 
strikingly so. Sometimes telangiectatic change in the blood-vessels is 
noted. Histologically these growths are characterized by round-celled 
masses surrounding the blood-vessels. The origin of the cells from the ad- 
ventitia may be evident or obscure. In cases in which a vascular network 
is involved and each vessel has a coating of sarcoma-cells a plexiform 
appearance or arrangement results {plexiform angiosarcoma). In other 
instances in which a network of vessels is involved the sarcoma-cells 
accumulate in the vascular meshes in the form of cell-nests, and thus 
give rise to an alveolar form {alveolar angiosarcoma). Such forms 
occur in sarcomata springing from moles or warts. They are prone to 
melanotic change. 

The angiosarcomata are liable to degenerations, chiefly myxomatous 
(Fig. 75) and hyaline, and thus a certain proportion of the cases of cylin-' 
droma (see below) have their origin. The blood-vessels may give way 
and hemorrhagic infiltration results. 

14 



210 



A TEXT-BOOK OF PATHOLOGY 



Angiosarcomata are, in a measure, benign, metastasis being very 
rare in the ordinary forms. The alveolar and melanotic varieties are 
highly malignant. 

Lymphangiomata are moist, gray, soft, spongy growths, commonest 
in the spleen. They are, however, quite rare. They consist of pro- 
liferated lymph-channels with well-marked swollen endothelial lining 
cells. 




Fig. 75. — Angiosarcoma with myxomatous degeneration: the figure represents one of 
the blood-vessels with the sarcomatous cells springing from its walls, and outside of these 
myxomatous tissue. 

Cylindroma 

This term was originally applied by Billroth to tumors showing 
gelatinous masses or trabecule traversing their substance. Histologically 
different forms of growths may be distinguished. We deal here only 
with sarcomatous or endotheliomatous cylindromata. 

The latter may be simply sarcomata in which hyaline or myxoma- 
tous degeneration has occurred in more or less insular fashion, or in 
which sarcoma and myxoma are peculiarly combined. Nearly always 
there is some hyaline change with the myxomatous. In most cases it is 
the angiosarcomata that present this peculiar condition. The sarcoma- 
cells surrounding the blood-vessels become converted into hyalomyxo- 
matous tissue or cause the formation of this. There result branching 
columns of hyalomyxomatous character traversing the sarcoma. In 
some cases the walls of the blood-vessels themselves may be the seat of 
hyaline change (Fig. 18), the proliferated sarcoma-cells surrounding the 
vessel being merely pushed aside. The term angiosarcomata myxoma- 
todes is given to these vascular forms. Cylindromata occur in the 
salivary glands, the brain, the lacrimal glands, and rarely in the sub- 
cutaneous tissues. In nature they are more or less benign. ; 



PROGRESSIVE TISSUE CHANGES 



211 



We have grouped in the following pages those tumors now believed 
to be sarcomatous alterations of the covering and lining of blood- and 
lymph- vessels. These tissues are derived from the mesoderm, as is the 
case with tissues giving rise to sarcomata, and resemble these tumors 
in their manner of growth. The individual cells approach, however, 
the epithelial or carcinoma type. 



ENDOTHELIOMA 

This tumor, which is also sometimes designated endothelial cancer, 
resembles cancer very closely in histological appearances in some cases. 
It affects the pleura, peritoneum, and membranes of the brain most 
frequently, but may be found in the skin, walls of the blood-vessels, 
periosteum, bone-marrow, lymphatic glands, gums, ovary, testicle, 




liver, and salivary glands. The serous membranes when affected become 
greatly thickened, tough, and white in color (Fig. 76), and irregular 
elevations or nodules may occur. Metastasis is infrequent, but the 
adjacent organs are sometimes involved, and occasionally more distant 
structures. Endotheliomata of the dura mater spring from the inner 
surface of that membrane and have a nodular character. The organic 
tumors of this nature form irregular nodules or infiltrating areas of a 
color varying from white to reddish depending upon their origin and con- 
struction. When they are of hemangio-endotheliomatous type, they are 



212 



A TEXT-BOOK OF PATHOLOGY 



pink to decided red and frequently pulsate. The paler ones are usually 
avascular and are thought by some to be derived from lymph-channels. 

Histologically endothelioma of vessels is characterized by more or less 
tubular or acinus-like aggregations or anastomosing columns of endo- 
thelial cells. The latter vary in character from those which are dis- 
tinctly endothelial to the most differentiated, which may be like typical 
'cylindrical epithelium (Fig. 77). Between these cellular columns or 
acini the connective tissue of the part affected may be seen in a normal 
state, though it is more frequently thickened by proliferation, and may 
grow into and around cell groups to such an extent that they seem ad- 
mixed or that the tumor cells degenerate. Those derived from small 




Fig. 77. — Microscopical section from the case shown in Fig. 76. 

vessels show a distinct band or column of cells surrounding the blood 
channel, abutting on the supporting connective tissue. They thus differ 
from the angiosarcoma in the limitation and compactness of the nests. 
In the endotheliomata of serous membranes inspection of the sections 
shows that the columns of epithelioid cells occupy subserous lymph-chan- 
nels, and it may be possible to demonstrate that the endothelium of 
the latter has been the starting-point of the cellular proliferation. In 
cases of carcinoma with penetration into the lymphatic channels it is 
notable, on the other hand, that the endothelial lining of the channels 
is uninvolved. On the other hand, there are cases, notably those of 
the dura, in which the superficial cells have almost certainly been the 
starting point of the growth. These elements multiply and elongate, 
forming definite fiber-like strands or even fibers, a property that is pos- 
sessed by endothelium generally. 

Psammoma 

This represents no distinct species of tumor growth, but rather a 
peculiarity of different kinds. The name refers to the presence of cal- 
careous matter like that of the brain-sand (acervulus cerebri), and psam- 
moma has sometimes been called acervuloma. The calcareous matter 



PROGRESSIVE TISSUE CHANGES 



213 



occurs in the form of rounded masses or concentrically arranged whorls. 
The tumor elements themselves may be fibromatous, gliomatous, sar- 
comatous, endotheliomatous, or even adenomatous or carcinomatous. 
In most instances it is endotheliomata that present these appearances. 
Psammomata are met with in the membranes of the brain, the choroid 
plexus, and the pineal gland. 

Tumors from Nerve Tissues 

The various elements of adult nervous tissue are the descendants 
of the ectodermic cells lining the neural canal of the embryo. The 
tumors arising in nerve tissues contain the different elements in vary- 
ing grade of differentiation, and the tumors are usually named from the 
state of development. Naturally, the gangliomata and those containing 
chromaffin cells are of a higher grade than the tumors composed of 
abnormally proliferating simple nerve-cells, a very rare occurrence, or 
of glia. The ganglionar growths and those of some structures like 
the adrenal medulla, whose genesis is closely associated with the ner- 
vous system, frequently contain cells whose protoplasm stains granular 
brown when fixed with chrome salts (chromaffin cells). 

The glioma when pure is a well differentiated tumor, and is of suffi- 
ciently frequent occurrence and clinical importance to warrant separate 
treatment. Glia tissue plays an important part in most neuroblastomata. 
The following classification is based upon those of Mallory and of 
Wahl. 

GLIOMA 

Definition. — The term " glioma" is applied to tumors composed 
of neuroglia with incompletely differentiated cells and many glia fibrils. 
It is difficult to draw a sharp line between the circumscribed tumors 
of this structure and the diffuse neuroglial' hyperplasia or gliomatosis 
met with in certain cases. (See section on Diseases of the Nervous 
System.) 

Etiology. — It is probable that congenital defects of development 
play some part in the causation of these tumors, particularly in the forms 
more frequently spoken of as gliosis. 

Appearance. — A typical glioma is usually a solitary tumor, rounded 
in outline, though its limits are difficult to determine, as it merges gradu- 
ally into the surrounding nervous tissue. Gliomata are somewhat 
harder than the normal brain substance, and often the color is a little 
different, either more grayish or pink or reddish. Sometimes they 
are quite vascular and dark red. The normal shape of the part may be 
little disturbed, or there may be indefinite elevation. In size the tumor 
varies up to masses as large as a lemon. Diffuse gliomatosis causes a 
swelling of the affected parts, sometimes quite regular, at other times 
irregular. When the spinal cord is affected its thickness may be con- 
siderably increased. On section, the area of gliomatosis is rather firm 
and grayish in color. Nearly always there is a tendency to excavation 
or cyst formation. In the cord this leads to the development of con- 
siderable cavities, as a rule communicating with the central canal. 



214 



A TEXT-BOOK OF PATHOLOGY 




Fig. 



78. — Glioma of the corpora 
quadrigemina (Perls). 



Seats. — Gliomata occur in the brain and less frequently in the spinal 
cord. In rare cases the cranial nerves have been involved (Fig. 78). In 
one case a glioma was found over the coccyx and sacrum, originating 
from the remains of the lower end of the neural canal. Glioma of the 
eyeball will be referred to below. Diffuse gliomatosis is particularly 

common in the cord. It is usually met 
with in the vicinit}^ of the cavities of the 
brain or cord. 

Structure. — The minute structure of 
glioma varies considerably according to 
the type of neuroglia represented. In 
the typical glioma the cells contain 
rounded or oval nuclei, and the proto- 
plasm is scanty. Polynuclear cells ma} r 
occur among the glia elements. The glia 
cells possess great numbers of exceedingly 
fine fibrils attached and separate from the interstitial fibrils. Wavy 
intercellular fibrils (neuroglia fibrils) lying parallel to the axis of 
the cells to which they belong are characteristic structures. They 
are not prolongations of the cells, but merely touch the cells at 
their sides, the extremities of the fibrils being free. These fibrils are 
distinguishable from the finer fibroglia fibrils of connective-tissue 
growths. The abundance of the fibrils varies in different gliomata, but is 
generally a rather marked feature. The more rapid the growth, the 
fewer the fibrils. These give the section a granular appearance when 
seen under low magnification. In other cases the cells are of the ependy- 
mal type, this source being considered probable because of the granu- 
larity of the cells, a condition often seen in actively growing or inflamed 
epend^ona, and the tendency of the elements to assume a columnar 
shape with a flat or curved base, and a free edge giving off fibrils. Ro- 
sette arrangement, about blood-vessels, may be encountered but these 
formations, however, constitute only a small part of the structure, the 
bulk being composed of round glia-cells. The number of cells and the 
density of the intercellular network vary greatly. As a rule, the cells are 
larger than the normal neuroglia cells, and sometimes they contain 
several nuclei. The tumor is generally quite vascular, and occasionally 
telangiectatic vessels may be observed. Secondary hemorrhages are 
prone to occur in the latter case. Softening may occur, and occasionally 
sarcomatous transformation has been described, though with doubtful 
propriety. Embryologically the glia is an epithelial structure, and 
gliomata should, therefore, be classified as epithelial tumors, and sarco- 
matous transformation is improbable. 

Diffuse gliomatosis has similar microscopical appearances, though 
the tissue is likely to be more compact and less vascular. In the spinal 
cord the process begins as a subepithelial proliferation of the glia at the 
posterior raphe of the central canal, the lining epithelium of this, at the 
same time, undergoing a certain amount of proliferation. Subsequently 
the gliomatosis increases and cavities form within. These may be lined 
with epithelial or epithelioid cells which are occasionally ciliated. Glio- 



PROGRESSIVE TISSUE CHANGES 



215 



matosis in the brain or cord may also present itself in the form of 
scattered nodular hyperplasias of the neuroglia. 

Nature. — Glioma is essentially benign. It is dangerous mainly 
on account of the pressure it exerts. Active proliferation and eccentric 
growth may occasion a considerable local malignancy in some cases. 
It is these that were formerly described as cases of sarcomatous trans- 
formation. The growth of the tumor is rather slow. They do not 
seem to give metastasis outside of the nervous system. 

Glioma of the Retina. — This tumor is a primary one of the retina, 
but may later extend to the eyeball and along the optic nerve. It is 
composed of round cells with large nuclei, often arranged around blood- 
vessels in a way suggesting the structure of angiosarcoma. This appear- 
ance is due to the fact that the cells surrounding the blood-vessels are 
preserved, while those at a distance are degenerated. In addition to the 
round cells, there are often found cells resembling epithelium in their 
appearance and their arrangement, the latter being that of epithelial 
rosettes. Ganglional cells have occasionally been discovered. The cells 
resembling epithelium have been regarded as derivatives of the outer 
layers of the retina, and the term neuroepithelioma has, therefore, been 
applied by some authors. Others regard it as a glioma in the strict 
sense of the word. In either case the origin of the tumor is undoubtedly 
ectodermic, and the growth must be classified among the epithelial 
tumors. It occurs most frequently in children, particularly in early life 
(two to four years), and often on both sides simultaneously. Family 
predisposition, in some cases, is very striking. Extension along the optic 
nerve or externally, and a tendency to recurrence after removal, indicate 
the malignant character of the growth. 

NEUROCYTOMA AND NEUROMA 

The foregoing tumors represent growths in which the supporting 
tissue of the nervous system is retained in its general character, but the 
physiologically active part of the system, the nerve cell and fiber, can also 
form neoplasms. As has been suggested the primal neurocyte of the 
ectoderm undergoes a metamorphosis through stages in which the nucleus 
enlarges and becomes more diffuse in its staining, the cytoplasm increases 
in relation to the whole element acquiring at the same time a more or less 
peculiar arrangement, and the growth of fibrils occurs. Recent studies 
would seem to indicate that a number of tumors have been detected which 
represent the various steps of this differentiation but they are not clearly 
separated from one another, especially those which correspond to the 
earlier stages. There are tumors on record composed entirely of cells 
corresponding to the primary neuroblast and without fibers, but these are 
exceedingly rare. The vast majority of cellular nervous tissue tumors 
resemble the more advanced differentiation of the cell as known in the 
mature ganglion or that correlative structure called the chromaffin cell, 
seen in the adrenal. Tumors of fibers alone, the common neuroma, are 
often seen but their exact genesis is not yet settled. By some they are 
looked upon as overgrowth of fibers alone, by others as a hyperplasia 
of the sheath of Schwann, by others as the remains of a neurocytoma 
from which the ganglion cells have disappeared. 



216 



A TEXT-BOOK OF PATHOLOGY 



The following headings will give the reader an idea of the principal 
tumors of nervous tissue but it should be remembered that gradations or 
mixtures occur and that much difference of opinion exists concerning the 
exact classification. In a tumor of the cord recently examined, areas of 
pure glioma were seen, a rosette of neurocytoma was encountered and one 
group of chromaffin cells was discovered. 

Neuroblastoma is a fairly rapidly growing and infiltrating tumor, at 
times reaching considerable size, occurring chiefly in the adrenal but also 
in the nervous system proper and tending to metastasize to the lymph 
nodes and the liver. The sympathetic system, distributed behind the 
peritoneum, seems to be the point of origin for most of those growths. 




Fig 79. — Canglio-glioma of corpus callosum. Note the large irregular, imperfect ganglion 
cells, the deeply staining round glia nuclei with large wavy hypertrophic fibrils. 

Children are most often affected but they may occur in adults. In struc- 
ture, they resemble sarcomata in that groups of imperfectly differentiated 
cells are found but usually search will show rosette arrangement and other 
characters to distinguish them. The principal cell is rather polymor- 
phous, the nucleus directing the shape, for this body is round, triangular 
or elongated with a narrow zone of cytoplasm about it. Imperfect fibers 
come off from the cell and there is a fairly distinct fibrous network but 
this is not ordinary connective nor glia tissue. The cells are usually 
arranged in rosettes but solid masses will often dominate a field. At 
times tumors of this class are made up of cells whose size would indicate 
a further differentiation. Such, it has been thought (Martius) represent 
immature cells of the sympathetic system. (Sympathoblastoma.) 



PROGRESSIVE TISSUE CHANGES 



217 



Ganglioneuroma or Glioma Ganglionare. — This tumor may arise from 
any nervous tissue but its more common appearance in the retroperitoneal 
region leads one to believe that it most often originates in the sympathetic 
system. It is a tumor of youth and is benign in the usual sense. Struc- 
turally the neoplasm consists of fairly well differentiated ganglion cells, 
with large compound nuclei or several nuclei, cells of the neuroblastic 
series varying from small deeply staining ones to the large pale cells of a 
neuroblastoma, and fibers chiefly without a myelin sheath. All these 
elements are well mixed, that is, without order or purpose. It is believed 
that the more nearly mature they are, that is, the more ganglion cells they 
contain, the more benign, while those resembling neuroblastoma are more 




Fig. 80. — Perineural fibroma. 

likely to prove malignant. At times there is a very marked overgrowth 
of glia cells and fibrils and some have thought that the tumor was the 
result of a glioma growing in sympathetic ganglia; this is probably not 
correct as there are too many undifferentiated neuroblasts in these 
tumors. Related to the foregoing is a tumor originating almost exclu- 
sively in the adrenal and carotid glands but possible apparently in 
other parts of the nervous system, in which large polymorphous chro- 
maffin cells form the outstanding feature — Chromaffin tumor or para- 
glioma. Such growths, benign in character, are only rarely found in 
elderly people and but seldom, as in the case of the carotid gland, call for 
surgical interference. The histology presents besides these chromo- 
philic elements, various stages of neuroblastic differentiation including 
ganglion cells and nerve fibers; glial elements are rare. These growths 



218 



A TEXT-BOOK OF PATHOLOGY 



usually show some hemorrhagic changes and may have degenerative 
cysts in them. 

The appearances of the foregoing tumors vary little from those of the 
gliomata ; that is, they are at times well outlined but when involving the 
central nervous system may fade into the surroundings or appear as 
multiple nodular condensations. The color is grayish or pinkish but 
may at times be hemorrhagic. 

Neuroma is the term now applied to tumors in which fibers predomi- 
nate although in a form known as ganglioneuroma or neuroma ganglio- 

cellulare, a large number of cells, even 
multinucleated, may occur. When the 
fibers are bare, the name neuroma 
amyelinicum is applied, where supplied 
by a medullary sheath, neuroma mye- 
linicum (Virchow). 

These new growths are to be dis- 
tinguished from neurofibroma or false 
neuroma which are endo- or perineural 
fibrous tissue formations; they will be 
discussed below. 

Neuromata appear as white firm 
nodular thickenings in the course of 
nerve trunks or at the nerve roots and 
rarely in the brain stem. Structurally 
they consist of masses of irregularly in- 
terwoven fibers in strands or singly with 
here and there what seems to be a glia 
cell or the remains or a neural cell of 
some sort. The question whether these 
tumors can be formed from fibrils alone 
or whether they need a governing and 
producing ganglion cell has not been 
settled, both sides being well represented 
in the discussion. 

Their nature is benign but they may 
affect the health of the patient by their 
painful character. They resemble fibro- 
mata very closely ; from such tumors they 
can be distinguished in the medullated 
variety by stains for myelin, while the 
amyelinic variety take the axis cylinder 
stains very poorly. 

Von Recklinghausen's disease, 
molluscum fibrosum or neurofibromatosis is a condition characterized 
by the growth in the skin of soft movable fibromatous masses about 
and in nerves, causing nodular elevations on the surface, sometimes 
literally in thousands. Although the first appearance of the growths 
may take place late in life, there is usually some hereditary influence 
and cases have occurred early enough to be called congenital. There may 
be other evidences of nervous or even mental disorder accompanying 




Fig. 81. — Case of von Reckling- 
hausen's neurofibromatosis (from a 
photograph by Dr. B. Lucke) . 



PEOGRESSIVE TISSUE CHANGES 



219 



these tumors. The skin over the fibromata and even about it may 
become thickened and relaxed and hang out in folds. Numerous patches 
of gray or brown pigmentation occur over the masses and between them. 

Grossly the masses appear as white or pearly gray nodules in the 
corium and fascia, or, when they attack nerve trunks, as diffuse swellings 
along the course of a single nerve or involving the whole plexus (plexiform 
neuroma). Occasionally gland-like irregular compound swellings occur 
independently of large trunks which have been fancifully called racemose 
neuroma. Under the microscope one sees a truly fibromatous growth 
of a cellular type surrounding small nerves and separating the sections of 
large nerves. The source of this new growth is probably the sheath of 
Schwann. 

While the above condition does not give pain or tenderness, there is a 
similar tumor of nerve endings in the skin that is quite painful. The 
growths are usually single but one of us saw a multiple painful form that 
was a combination of the above condition except that the tumors might be 
called liponeurofibromata. Single fibromata of nerves occur in nerve 
roots and on cranial nerves. 

False neuromata are seen after traumatism and amputation. The 
damaged nerve in its attempt at regeneration forms at first an extensive 
growth of connective tissue into which axis cylinders try to grow. Al- 
though the nerve sheath forms a medullary covering, there is so much 
atypical overgrowth and surrounding scar tissue that the nerve cannot 
continue to its end organ, if there be one, which is not the case after 
amputation. There is thus formed a nodular firm white mass on the 
damaged nerve or at the end of a severed one, which microscopically 
consists of twisted nerve fibrils, with and without myelin, in a disorderly 
arrangement and in excess. The newly formed tissue is, however, adult 
and no really undifferentiated structures are to be found. It is therefore 
not a tumor but a regenerative process perverted by scar tissue. 

Chordoma. — This is a very rare lobulated tumor arising from the 
sphenoid bone or at times over the anterior occiput and in the sacral 
region, derived from remnants of the chorda dorsalis. While most of the 
cases are small and with no consequences, some of them have grown 
progressively, compressing important structures and causing bone 
absorption. Structurally they resemble myxomata and chondromata, 
therefore being difficult of exact determination. They show large 
vacuolated cells lying in groups or strands and supported by a hemo- 
genous loose spongy ground substance. 

LEIOMYOMA 

Definition. — Leiomyoma, or myoma lsevicellulare, is a tumor 
growing from smooth muscle-fibers. Nearly always there is a cer- 
tain amount of fibrous tissue associated, and in the most common form, 
myomata of the uterus, there is always considerable fibrous tissue, and 
the term "fibromyoma" is appropriate. Occasionally a few unstriped 
muscle cells may be seen in tumors of other kinds. 

Etiology. — While the relation of irritation to myoma formation is 
not clear it is about the only factor which precedes any number of cases. 



220 



A TEXT-BOOK OF PATHOLOGY 



In the uterus the growth occurs during late menstrual life and may dis- 
appear spontaneously after the menopause. Some would ascribe an 
etiological role to the irritation of remains of the Wolffian body but this 
is speculative. 

Appearance. — Leiomyomata are usually rounded growths, vary- 
ing in size from minute nodules to huge solid masses weighing as much as 
60 to 70 pounds. The largest (heaviest) solid tumor ever seen by us was 
a degenerated flbromyoma wegihing 80 pounds. Leiomyomata are 
surrounded by a capsule more or less well developed and are generally 
quite hard, though secondary degeneration at times alters the consistency 
making the tumor quite soft in the case of mucoid transformation, or 
stony hard when calcification has occurred. On section through the 
growths the stratified or fasciculated arrangement of the cells is visible to 
the naked eye. Concentric layers may be apparent, or a more wavy 
irregularity may be seen. They are grayish or flesh colored, or in rare 
instances quite red (myoma cavernosum), in consequence of enlarged 
vascular channels. Central softening may lead to cystic change (myoma 
cysticum) . 

When the myomata spring from the submucous or subserous tissues 
they may become polypoid, hanging from a point of attachment by a 
narrow pedicle. In rare instances the latter is severed and the tumor 
becomes a free body. Submucous myomata of the uterus may thus 
eventually be discharged after a spurious labor. Subserous myomata 
may become free in the peritoneal cavity. 

Gross myomata of the uterus may have three situations — submucous, 
subserous, or interstitial. Originally, all true forms begin as interstitial. 
In the latter the tumor occupies the wall of the uterus without any 
particular projection on either surface. Uterine myomata are usually 
multiple, occur during the third and fourth decades of life, continuing 
their growth until the menopause, and usually decreasing after that 
epoch. They endanger life by their pressure and by the copious uterine 
hemorrhages which they occasion. Very frequently salpingitis is asso- 
ciated, and recently attention has been called to degenerated conditions 
of the myocardium in patients suffering from uterine fibroids. 

Myomata of the skin occur in younger patients, even in childhood, 
and are generally multiple and often painful (tubercula dolorosa). 

Seats. — The common situations are the uterus, the gastro-intestinal 
tract, and the ovaries; the less common seats are the walls of 
the blood-vessels, the skin, and the nipple. In all situations the tumor 
springs from pre-existing unstriped muscle-fiber. In most cases, accord- 
ing to some authors, the origin is in the walls of the minute blood-vessels, 
but direct origin from the muscular layer of the affected organs, or from 
the erectores pilorum in the case of the skin, cannot be denied. Myo- 
matous metaplasia of the connective tissue, as in the case of myo- 
mata originating in the areas of old pleural thickening, has been assumed 
but is improbable. 

Structure. — Microscopically, the tumor presents a characteristic ap- 
pearance. Bundles of muscle cells are seen running in different direc- 
tions. Those cut longitudinally show cylindrical nuclei as the most 
conspicuous feature, the outlines of the cell being indistinct (Fig. 82). 



PROGRESSIVE TISSUE CHANGES 



221 



The protoplasm stains well with eosin. Lying between the muscle cells 
are collagen and so-called myoglia fibrils, the latter being coarse lines 
lying along the side of the cells, while the former are more delicate and are 
associated with fibrous tissue cells. The picture of a leiomyoma is often 
suggestive of sarcoma, but may be distinguished by the greater regularity 
in direction of the cells in different bundles and by the more distinctly 
cylindrical outline of the nucleus. The cells of leiomyomata may be 
isolated by maceration of the sections in 20 per cent, solution of nitric 
acid for twenty minutes, or in 30 
per cent, solution of caustic pot- 
ash for fifteen minutes. They are 
spindle-shaped structures contain- 
ing a nucleus about one-third the 
length of the entire cell. On sec- 
tion they can be differentiated 
from fibrous tissue cells by showing 
an appreciable amount of proto- 
plasm around a rod-shaped nucleus, 
while the connective-tissue cell 
has very little protoplasm about 
a short spindle-shaped nucleus. 
Considerable elastic tissue is found 
in some leiomyomata, especially 
in the younger areas. 

Although in rare instances a telangiectatic condition of the vessels is 
seen, vascular channels are usually only of fair size at the periphery and 
become smaller toward the center of the growth; thus is explained the poor 
nourishment of the central portions and their tendency to hyaline or to 
necrotic changes, sometimes with the production of cyst-like softenings. 

Of the degenerative changes, calcification is the most common, par- 
ticularly in the uterine fibromyomata. This begins in the center of the 
tumor, but may eventually involve the whole mass. Dilatation of lymph 
channels, with the formation of cystic spaces containing spontaneously 
coagulable material, is known. 

Myxomatous change may occur in myomata containing much fibrous 
tissue, and sarcomatous transformation has been described, but is rare. 
The sarcomatous change has been explained by some as a metaplasia 
of the muscle cells, by others as arising from fibroblasts. The latter is 
probably correct. Many so-called sarcomata coming from smooth 
muscle tumors are doubtless merely actively proliferating, therefore 
softening, leiomyomata. 

Uterine myomata do not all present the same appearance. Some are 
all of muscular nature, some are wholly fibrous, and we have all possible 
intermediate grades. Those in which fibrous tissue preponderates may 
be called "fibroids." Young tumors are mostly muscular; old ones, 
mostly fibrous. Whether this is purely a metaplasia or an overgrowth 
of the muscle by fibrous supporting tissue is not settled. The origin 
of the myomatous tissue is said by some not to be the uterine muscle 
bundles, but the muscularis of blood-vessels. The vessels of myomata 
have very thick walls with wide muscular coats. 




222 



A TEXT-BOOK OF PATHOLOGY 



Adenomyoma of the uterus is a myoma with structures like gland 
acini. These are variously explained as coming from remains of the 
Wolffian body or Muller's duct, from the mucous glands, or inversions 
of the serous covering. They may undergo carcinomatous increase, but 
adenomyomata are not malignant per se. 

Nature. — The nature is eminently benign. Myomata of the 
digestive tract may cause occlusion or strangulation, or by their weight 
may exercise serious traction. Uterine myomata are dangerous in the 
ways already indicated. The growth is usually slow. 



RHABDOMYOMA 

Definition. — Rhabdomyoma, or myoma striocellulare, is a tumor 
containing more or less striped muscle-fiber. Ordinarily there is but a 
small quantity of the latter, the bulk of the tumor being of some other 
tissue, usually resembling sarcoma. 

Etiology. — Congenital defective development seems an important 
cause, as the tumors occur in early life and in situations in which striped 
muscle-fiber does not normally occur. 

Appearance and Seats. — The rhabdomyomata of the kidney 
(the most frequent seat) present themselves as large rounded or irregular 
masses, more or less encapsulated. In the testicle they are similar, 
though of smaller size. A few cases have been described in which irregu- 
lar tumors of the retroperitoneal tissues have contained muscle-fibers. 

There is a form arising in the heart wall growing in a nodular or 
polypoid manner sometimes hanging within the heart. On section such 
tumors are soft and grayish, the surface of the cut being marked by 
alternate brownish areas of muscle and pale zones of connective tissue. 
The more cellular the tumor, the softer, the more reddish and 
opaque. 

Structure. — The microscopical appearance resembles that of a 
spindle-celled sarcoma, containing more or less striped muscle-fibers. 
These are elongated spindle-shaped cells, partly striated, and suggesting 
embryonal muscle-tissue and rarely more fully developed muscle-fibers. 
Large areas of the tumor may contain no muscle-fiber at all, while 
certain portions are richly supplied. The nuclei of the muscle cells are 
large, loose and of very varying distribution. They seem to lie near an 
end of the fiber or upon its periphery at times. The sarcolemma in the 
mature fibers is clear while in the poorly differentiated elements it maybe 
absent. As the muscle cells are at times wholly undifferentiated they 
resemble very much embryonal connective tissue cells of large size, and 
therefore suggest sarcoma. Adenomatous elements are not rarely asso- 
ciated, either because of the organ in which the tumor arises or because the 
newgrowth had a teratomatous origin. 

Nature. — These tumors are malignant in proportion that they con- 
tain sarcoma-like embryonal elements and therefore fewer striated fibers. 
This sarcomatous nature is indicated by activity of proliferation, spread, 
and metastasis. Metastasis is, however, infrequent. General cachexia 
and hemorrhages reduce the vitality and lead to fatal termination. 



/ 



PROGRESSIVE TISSUE CHANGES 223 

Epithelial Tumors 

This heading covers all the tumors in which the cellular unit is the 
epithelial cell of covering or glandular tissues, supported by more or less 
connective tissue, the relations of the two determining the character of 
the growth. In some arrangements there is simply an exaggeration of 
the normal, the so-called typical epithelial growths, while in others there 
is wholly new or atypical arrangement of the elements. The first, like 
papilloma, are essential benign, while the second group is best exempli- 
fied by the malignant carcinoma. It should be emphasized that these 
tumors are purely cellular in their essential structure, that is the fibrous 
supporting tissue is passive and exists only as stroma about or beneath 
epithelial groups. Nor do fibers grow between individual cells but only 
divide accumlations into nests or alveoli. 

PAPILLOMA 

Definition. — The term " papilloma" indicates a tumor arising from 
a surface and covered with epithelium somewhat as the epidermis caps 
the papillae of the corium. 




Fig. 83. — Various grades of warts and cutaneous papillomata (Perls). 

Etiology. — It is difficult to draw a line between certain papillo- 
matous growths that are the result of chronic irritation and others that 
arise in a seemingly spontaneous manner. It would appear that irri- 
tation is an important factor in most, if not all, cases, but there is also, 
no doubt, some form of predisposition. Whether this resides in structural 
peculiarities or not is difficult to determine. A peculiar form of inflam- 
matory growth resembling the spontaneous papillomata is that known as 
venereal wart. It occurs about the genitalia or anus and especially after 



224 



A TEXT-BOOK OF PATHOLOGY 



gonorrhea. Another form of inflammatory papillomata is that found in 
the mucous membranes surrounding carcinomata or chronic ulcerations 
of syphilitic or other kinds (Fig. 83). 

Appearance. — The most familiar form of papilloma is that which 
occurs in the skin and which is commonly called wart. Warts or 
papillomata may be single, but more frequently occur in groups, and there 
may be many growths in widely scattered areas of the body. A wart 
may be simply a smooth hemispherical elevation, or it may have a 
cauliflower appearance. The epidermis covering it is, as a rule, somewhat 
more granular or rough than that of the normal skin. The size of 
these growths varies from minute points to nodules as large as a walnut. 

On the mucous surfaces, especially where 
the epithelial covering is columnar, the 
papilloma presents itself as a soft and more 
distinctly cauliflower growth (Fig. 84). 
It is red in color, or, if the epithelium is 
stratified and squamous, grayish or pink. 
The growth is usually comparatively hard 
when covered by squamous epithelium. 
Those in the aliment aiy mucosa may 
appear as polyps. 

Two varieties are sometimes dis- 
tinguished: the hard papillomata, such as 
those which occur in the skin; and the 
soft papillomata, or the form usually seen 
in the mucous membranes. 

Seats. — Papillomata occur in the skin 
of the neck, hands, back, and other parts, 
and in the mucous membranes, particularly 
in the bladder, larynx, nasal chambers, 
and gastro-intestinal tract. Small papillo- 
matous outgrowths may spring from the 
lining membrane of glandular ducts, as 
in the breast or ovary. These may lead 
to subsequent cystic change in the organ, 
or they may arise after cystic change has begun by proliferation of the 
lining membrane of the cyst. In a similar manner papillomatous eleva- 
tions may occur within the cavities of cystic adenomata (see below). 

Structure. — The essential parts of papilloma are the center or 
groundwork of connective tissue containing blood-vessels and the epi- 
thelial covering. In the skin the growth imitates the normal papillae, 
all portions of the latter, however, being greatly exaggerated, and the 
papilla with its covering of epidermis being raised above the surface 
instead of having its usual seat below the surface with the epidermal 
covering level with the surrounding parts. When there is tendency to 
cauliflower appearance the papilloma shows a branching form on vertical 
section. Each of the branches contains a connective-tissue framework 
with an epithelial covering. The latter consists of stratified, squamous 
cells and shows a decided tendency to horny change. Distinct concentric 
whorls of horn}^ epithelium, such as occur frequently in epitheliomata of 




Fig. 84. — Papillomata of the 
vocal cords (from a specimen in 
the Museum of the Philadelphia 
Hospital) . 



PROGRESSIVE TISSUE CHANGES 



225 



the skin, may be met with in papillomata. In some cases the amount of 
connective-tissue groundwork in the papilloma is excessive; in others 
the new growth consists almost entirely of proliferated epithelium. In 
some of these latter cases the resemblance to epithelioma may be quite. 




Fig. 85. — Finer details of papilloma, showing connective stalk and stratified squamous 

epithelium. 

suggestive, but a distinction can be made by observing that the tumor 
tends to grow outward rather than into the deeper structures, and always 
shows some connective-tissue stroma at least. The papillomata of the 
mucous membranes differ according to their situation. In the larynx^and 




Fig. 86. — Papilloma of the scalp. The branching fibrous stroma is covered oy an abnor- 
mally thickened, irregular epithelium (Boyce). 

other portions covered with squamous epithelium they may present much 
the same appearance as that seen in the skin, though the epithelium, 
as a rule, remains softer. There are cases, however, in which a distinct 
pachydermatous change is found in the epithelial covering of papillomata. 

15 - 



226 



A TEXT-BOOK OF PATHOLOGY 



In the gastro-intestinal tract and in the bladder papillomata are prone to 
be soft and villous in appearance and are covered with a scantier epithelial 
coating. Cystic change is not unusual as a result of degenerative processes 
or of distention of the mucous glands. Occasionally hemorrhage occurs 
from papilloma, particularly of the villous variety. Melanotic pigment 
is sometimes found in warts. 

Nature. — The nature of these tumors is benign, but they may be 
destructive of the general health in consequence of repeated hemorrhages 
or by interfering with the function of the organ or part in which they are 
situated. In some cases they are supposed to become malignant, but this 
has not been definitely proved. 

ADENOMA 

Definition. — This is the term applied to a new growth correspond- 
ing more or less in structure with compound epithelial glands, and, 
therefore, presenting acini or tubules containing glandular epithelial 
cells (cylindrical or polyhedral) growing upon a basement-membrane, 
and a reticulum of connective tissue and blood-vessels. It is difficult 
to separate from true adenoma simple glandular hyperplasia on the 
one hand and carcinoma on the other. This will be discussed in re- 
ferring to the structure. 

Etiology. — The causation of adenoma is obscure. In some cases 
congenital misplacements of tissue-elements appear to play a part, 
as is seen in the cases of adenomata of the kidney having the structure 
Of suprarenal bodies. These tumors which, it is true, some authorities 
refuse to consider as adenomata, have a general resemblance to adeno- 
mata and spring from remnants of suprarenal tissues embedded in 
the kidney substance. Traumatism may be a factor in the etiology 
by exciting the proliferation of such misplaced tissue elements. In 
other cases the ordinary glandular structures seem to be stimulated to 
abnormal hyperplasia and tumor growth in consequence of continued 
irritation. Instances of this sort are frequently seen in the gastro- 
intestinal mucous membranes, notably in the stomach and lower part 
of the colon, in certain cases of chronic gastritis and old dysenteries. 

Appearance. — The appearances of adenomata vary greatly with 
their seat. On the mucous surfaces there may be a simple thickening 
or more or less diffuse and irregular elevation of the surface, or in other 
cases distinct papillomatous outgrowths and rarely definite nodular 
tumors. In the substance of the organs adenomata occur as nodular 
tumors, usually singly and well circumscribed, and not rarely surrounded 
by a fibrous capsule. They are moderately firm, and on section whitish or 
pink in color. Sometimes cystic change occurs as the result of dilatation of 
the glandular acini or in consequence of degenerative softening; in these 
cases the consistence is correspondingly altered. 

Seats. — Among the situations in which adenoma is frequent may 
be mentioned the mucous membranes, the skin, and certain organs, 
notably the mammary gland, liver, kidney, suprarenal bodies, thyroid 
gland, and ovaries. Clinically important seats are the pylorus, the duo- 
denal papilla, the rectum, and the uterus. In these situations adenomata 



PROGRESSIVE TISSUE CHANGES 



227 



spring from the epithelial tubules or mucous glands. In the skin the 
points of origin are the sebaceous and sweat-glands. 

Structure. — The definition in general indicates the structure 
of these tumors. They are more or less typical; that is to say, there 
are acini of normal appearance presenting a single layer of columnar 
epithelium, with perhaps in places a tendency to heaping up the several 
rows of epithelial cells. In the simple adenomata there is usually one 
layer. The greater the number of layers of epithelial cells, the greater 
the tendency to malignant growth; such a condition is found in adenoma 
malignum along with other features. The acini are well inclosed by 
a surrounding connective-tissue reticulum, and the appearance of normal 
gland tissue is thus produced. Unlike normal glands, there are no 
excretory ducts, or, at most, imperfectly developed ducts. 




Fig. 87. — Destructive adenoma (Beyea). 



Two varieties of adenoma are sometimes distinguished; the tubular 
and the racemose or alveolar. In the former the glandular system is 
simple and consists of tubular formations lined with columnar epithelial 
cells; in the latter the appearance is that of more complicated glands 
with closely aggregated acini of circular outline containing columnar 
and often cubical or polyhedral cells. The number of varieties may be 
carried further, however, for in the liver the adenomata resemble the 
normal liver structure rather than the ordinary glandular formation 
above described. In the suprarenal capsules and kidney the appear- 
ance is that of slightly atypical suprarenal structure, or in other cases 
that of embyronal renal tubules distended to form considerable cystic 
spaces, with partitions and inwardly projecting papillomatous elevations. 

With the further growth of adenomata the appearance may be little 
changed. In some cases considerable variations occur, and there is a 
tendency, more marked in some situations than in others, to active pro- 
liferation of the epithelium, which may cause a considerabe alteration 
in the histology of the tumor, and eventually transformation into definite 



228 



A TEXT-BOOK OF PATHOLOGY 



carcinoma. The terms " adenocarcinoma, " " destructive adenoma, " and 
"malignant adenoma" are sometimes applied in such cases. The same 
names, however, are given to a type of adenoma characterized by the 
formation of abundant anastomosing or separated tubules and acini 
with comparatively little reticular tissue, and by the tendency to repe- 
tition of the same structure in the local extensions from the original 
growth and even in metastases (Fig. 87). 

The connective-tissue stroma of adenomata may be moderate 
in quantity or may be considerable. In some adenomatous prolifera- 
tions of the mucous membranes the number of gland acini or tubules 
may be relatively small, while the interglandular connective tissue 
shows active round-cell infiltration to a very considerable degree. 
Sometimes the interglandular tissue is distinctly sarcomatous (adeno- 




Fig. 88. — Adenoma of the mammary gland, with cystic enlargement of acini and abundant 
interglandular hyperplasia of connective tissue. 

sarcoma). In other instances the bulk of the tumor may consist of 
connective tissue of fibrous character in which are embedded a rela- 
tively small number of glandular alveoli. In all of these cases it is 
difficult to determine whether the connective-tissue process was pri- 
mary and the epithelial secondary, or the reverse. 

As has been suggested, it is well-nigh impossible to distinguish between 
some adenomata and some hyperplasias. This is particularly true of 
hyperplastic growth without ' fibrous tissue. This condition is, how- 
ever, apt to follow the general architecture of the gland in question 
and is not apt to be encapsulated. The adenomata have a tendency to 
show small, normal sized, and cystic acini in the same field. It is like- 
wise a task to differentiate chronic inflammation and fibro-adenoma. 
In the former nearly all gland tissue is compressed and cysts are rare. 



PROGRESSIVE TISSUE CHANGES 



229 



When present they soon loose their epithelium. In fibro-adenoma epi- 
thelial reduplication is pronounced and the fibrous tissue increase is 
more diffusely distributed. 

Secondary changes are common, the adenomata of the stomach and 
uterus being particularly prone to change their character to that of 
carcinoma. In these cases there may be noted active proliferation 
of the epithelial cells, so that acini or alveoli become completely filled, 
or that the ends of tubular structures become blocked up. There is 
a tendency to extension of epithelial infiltration beyond the limits of 
the acini, cancerous outgrowths being the result. In other cases the mal- 
ignancy is manifested by the excessive epithelial proliferation in the 
form of new acini of irregular character (see Fig. 88). Eventually the 
tumor may become purely carcinomatous; in other cases, however, it 
continues to increase in size, always retaining its adenocarcinomatous 
appearance, but never becoming typically carcinomatous. 

Degenerative changes may be met with in adenomata as in other 
tumors. Hyaline transformation or production of hyaline or myxoma- 
tous tissue in the stroma may give the tumor an appearance justifying 
the term "cylindroma" or "cylindro-adenoma." Such cases are rare. 
Myxomatous and even calcareous change may sometimes be observed. 
The connective-tissue stroma may proliferate actively and assume sar- 
comatous appearance — adenosarcoma. Cystic change may result from 
gradual dilatation of the glandular acini or from distention of normal 
ducts or alveoli of the gland in which the tumor occurs. In these cases 
the terms "cystic adenoma" or "cystadenoma" are applicable (Fig. 88). 

Nature. — Adenomata are benign tumors. In some cases, however, 
a pure adenoma may give rise to metastasis. Those of the liver, for 
example, not rarely cause secondary deposits in the spleen and less 
frequently elsewhere. The adenomata of the thyroid gland similarly 
cause metastasis, though their structure does not in any w T ay suggest a 
malignant growth. Destructive adenocarcinomata or adenomata are 
malignant in proportion to the amount of carcinomatous transformation 
on the one hand, or of atypical glandular proliferation on the other. 

The effect of adenomata on the general health is variable. They 
do not contribute to the general metabolism as far as is known, though 
occasionally biliary pigmentation of the adenomata of the liver, and 
even of their metastases, and the secretion of milk-like fluid in mammary 
adenomata evidence the partial preservation of function by the cells. 
The general health may be unfavorably influenced by adenomata of 
the mucous surfaces in consequence of their interference with normal 
functions or in consequence of secondary ulceration and hemorrhage. 

CARCINOMA 

Definition. — The terms "carcinoma" or "cancer" may be applied to 
tumors in which epithelial proliferations in the form of solid blocks or 
columns, or in the form of atypical acini, separated by more or less con- 
nective tissue, present themselves, the epithelial proliferation showing 
a tendency to extend beyond normal anatomical limits. It is extremely 
difficult to construct a definition that will be universally applicable. 



230 



A TEXT-BOOK OF PATHOLOGY 



Some have regarded the tendency of the epithelial proliferation to break 
through the normal limits, and extend beyond the confines of the epi- 
thelial structures from which it rises, as the important fundamental 
element of carcinoma. Others have held that there is a peculiar atypical 
character in the epithelial cells themselves, shown by irregular cell 
division, hyperchromatosis, and other features. The older authors 
believed that polymorphism and certain irregularities of cell contour 
suffice to distinguish carcinoma-cells from normal cells or those of other 
tumors ; but this polymorphism is now recognized to be the result entirely 
of compression in the growth of the tumor, and to be, therefore, accidental. 
Some have believed that the term "carcinoma" should include all epi- 
thelial tumors giving rise to metastasis, but this necessarily restricts 
the term too greatly on the one hand, and, on the other, includes cer- 
tain tumors probably purely adenomatous. We prefer to regard as car- 
cinoma any epithelial growth atypically reproucding certain glandular or 
other structures and showing a manifest tendency to irregular extension. 

Etiology. — The causes and nature of carcinoma are still obscure. 
A number of theories have been offered. These have been referred to 
in the discussion of the etiology of tumors in general. A brief reconsider- 
ation may be useful in this place : 

(a) Congenital Theory. — The theory of Cohnheim regarding the 
etiology of tmors in general is less applicable to cancer than to certain 
other growths. There are a few examples, however, which would seem 
to prove that misplaced epithelial cells undergo carcinomatous pro- 
liferation; for example, there are cases of apparently primary carcinoma 
springing from bones which would seem to require this explanation. 
It is not always certain, however, that such cases are actually primary. 
The rarity of carcinomata in early life would seem to negative the 
congenital theory, and, at all events, would show that other influences 
of importance are requisite. 

(b) Traumatic Theory. — Clinicians are inclined to give great weight 
to this. A single traumatism probably has little importance, though 
women frequently state that they recall distinct injuries from which 
carcinomata of the breast have seemed to originate. It must be recalled 
that such injuries are sustained by practically every woman, and the 
presence of carcinoma would readily be attributed to a preceding hurt. 
In cases of epitheliomata of the lip in pipe-smokers, in the carcinomata of 
the scrotum and limbs in chimney-sweeps and paraffin-workers, in the 
skin of tar workers, and in cases of uterine carcinomata following lacera- 
tion of the cervix, the effect of chronic irritation would seem to be im- 
portant. The frequent association of gall-stones with carcinoma of the 
gall-bladder has often been considered in the same light. 

(c) Infectious Theory. — The peculiar growth of cancer, its destruc- 
tiveness of the general health, and its metastasis readily suggest an 
infective origin. Bacteriologists sought to isolate micro-organisms 
without success; later investigators have turned their attention to low 
forms of animal life — protoza. (For further discussion, see p. 168.) 

(d) Tumor Dyscrasia. — This indefinite term is supposed to indicate 
that certain peculiarities of the liquids of the body occasion the tend- 
ency to cancerous growth. No proof of the existence of any definite 



PROGRESSIVE TISSUE CHANGES 



231 



dyscrasia has ever been furnished, though it is not unlikely that some 
form of disposition to this growth acts as the predisposing cause, even 
if traumatism, infection, or other factors are the immediate cause. 

Certain conditions are supposed to precede and favor some cancers. 
Paget's disease of the nipple may precede mammary cancer, as also 
gastric ulcer may pave the way for carcinoma of the stomach. Previous 
benign epithelial growths may become carcinomatous, as indicated by 
their penetrative and greater proliferative powers, but not necessarily 
by any alteration of the cells themselves. 

Age plays an important part in the formation of carcinoma, as this 
tumor is essentially one of advanced years. Among 275 cases collected 
by Lubarsch, 55.6 per cent, occurred between the ages of forty-five and 
sixty-five. There were a few instances in childhood and early life. Be- 
tween fourteen and nineteen there were 1.46 per cent.; between twenty 
and twenty-five, 1.8 per cent.; between twenty-six and twenty-nine, 
1.1 per cent. The frequency in later life was formerly ascribed to some 
alteration in the vitality of the epithelial cells, rendering them more 
liable to abnormal proliferation. The nature and cause of such altera- 
tion, however, remain obscure 
and theoretical, though there 
is certainly a greater tendency 
to cancer growth as age 
increases. 

Heredity was formerly re- 
garded as of great importance, 
but there is probably no 
reason to ascribe any more 
influence to this for carcinoma 
than for tumors in general. 

Appearance. — Carcino- 
mata differ considerably in 
appearance in different parts 
of the body. Those of the 
surface present themselves as 

more Or less nodular, flat Fig. 89.— Carcinoma of the duodenal papilla 
elevations. In the skin the (modified from Kast and Rumpel). 

nodules may remain hard and 

rather smooth, or they may soften upon the surface, forming un- 
sightly ulcerations. In the mucous membranes the growths are 
more frequently soft and polypoid or cauliflower excrescences (Fig. 
89). Ulceration may occur on the surface of such elevations, or from the 
first the tumor may be of ulcerative character, causing spreading ex- 
cavations limited by thickened projecting edges. Carcinomata of the 
glandular organs form more or less nodular tumors or irregular infiltra- 
tions. These vary greatly in consistency, some being almost stony hard, 
others soft in consequence of their preponderating cellular character or 
of secondary degenerations. On section, the tumor is found to be white 
or grayish in color, generally somewhat translucent and glistening; 
milky, liquid may ooze from the surface. Capsule formation is rarely 
seen, though in occasional instances the normal connective tissue of the 




232 



A TEXT-BOOK OF PATHOLOGY 



organ is pressed outward by the growth of the tumor, and thus forms an 
imperfect capsule. The primary growth is generally solitary. Occa- 
sionally instances are observed in which two separate masses develop 
simultaneously and apparently independent of each other, as in the two 
breasts. More frequently apparent multiplicity is caused by the early 
appearance and rapid growth of metastases. 

Secondary carcinomata are nodular in character and nearly always 
multiple. The larger are often distinctly encapsulated. Central 
softening or contraction of connective tissue may give the surface of 
the nodule an umbilicated character (Fig. 90). The number varies 
greatly, from a few large or small nodules to innumerable tubercle-like 
forms in general carcinomatosis. In some situations, as in bones, second- 
ary carcinoma has an infiltrating character. 




Fig. 90. — Metastic nodules of carcinoma on the surface of the liver (Hanot and Gilbert). 

Seats. — The situations in which carcinomata occur are very numer- 
ous; they invariably arise from pre-existing epithelial structures. In 
the rare instances in which a really primary carcinoma has occurred 
in bone or other connective tissues the presumption is warranted that 
the tumor originated from remnants of epithelial tissue left by faulty 
development. Among the frequent places of origin the most important 
are the uterus, the skin, the gastro-intestinal tract, particularly the 
esophagus, pylorus, and rectum, the mammary gland, the ovaries; less 
frequently the liver, kidney, thyroid gland, prostate, or testicle may be 
the starting-point. Secondary carcinomata curiously do not often affect 
parts in which the primary growth is frequent. Of the many seats of 
secondary carcinoma, the lymphatic glands, the liver, spleen, lungs, 
heart, arid serous membranes are the most important. Secondary 
carcinoma of the bones is specially frequent after carcinoma of the breast, 
the thyroid gland and prostate. 

Structure. — The histology of carcinoma varies greatly in different 
situations and in different forms. There are two distinct elements in- 
volved — viz., epithelial cells and a connective-tissue stroma. The 
epithelial cells are medium sized or large, and have a rather large and 



PROGRESSIVE TISSUE CHANGES 



233 



clear nucleus; the shape of the cell, however, differs widely. In epi- 
theliomata of the skin the cells are large and usually of a squamous 
variety. In carcinomata of mucous membranes they are more often 
cylindrical or columnar, and there is a tendency to the formation of cu- 
boid or polyhedral epithelium. The last-named forms are habitually 
present in the cancers of glandular organs. The mutual compression 
exercised may occasion a polymorphous character, and the older writers 
wrongly regarded this as a feature by which a carcinoma-cell could be 
recognized as such. Secondary changes may occasion wide variations 
in the appearance of the cells; thus, the epithelia of cancers of the skin 
tend to become arranged in concentric whorls and at the same time 




Fig. 91. — Epithelioma of skin, showing concentric arrangement and degeneration of cells. 

to become somewhat glistening from horny transformation (Fig. 91). 
The nucleus may be clear and quite structureless, or may show a dis- 
tinct nucleolus and a definite chromatin network. Karyokinetic fig- 
ures may be quite abundant and are frequently atypical. Degenerative 
changes (dropsical infiltration, myxomatous change, fatty degeneration) 
may alter the nucleus as well as the body of the cell. 

The epithelial cells are usually grouped as cylindrical and branching 
or anastomosing columns, or as irregular tubular formations, the tubules 
being of varying lengths. The explanation of the structure of the col- 
umns or tubules is that they are formed by the extension of the masses 
of proliferated cancer-cells along the lymph-channels and spaces of the 
tissue. Very often the section shows all the tubules cut transversely, 
and thus the appearance of glandular acini is given. In some cases the 
tubules are short and acinus-like; as a rule, however, the appearance is 
only due to the manner of section. The acini differ strikingly from those 
of adenoma in showing several or many layers of cells instead of one, 



234 



A TEXT-BOOK OF PATHOLOGY 



and there is the further difference that cellular outgrowths may be seen 
at the periphery of the acini, the cells having broken through the 
retaining wall (basement-membrane) and proliferated outside to form 
new clumps. On examination of the epithelia within the acini it is found 
that those of the peripheral layer frequently retain the columnar char- 
acter seen in the normal alveoli of the gland from which the tumor springs. 

The connective-tissue stroma of carcinoma is more or less dense, 
but practically is always of fibrous character. It is arranged in such 
manner as to form hollowed spaces or columns in which the epithelial 
structures already described are embedded. The connective tissue 
carries the blood-vessels. The lymph-vessels probably connect directly 




Fig. 92. — Keratinization in cylindrical cell carcinoma of esophagus. 

with the cell-nests. In general, the more connective tissue in a cancer, 
the less its malignancy; while the more cells, the greater its tendency to 
metastasis and recurrence. Recently attention has been called to the 
fact that elastic tissue is formed in the stroma of the tumor in varying 
abundance. Frequently infiltrating leukocytes and plasma-cells or 
mast-cells are seen within the stroma. When the stroma begins to 
grow and show atypical proliferative tendencies we have what is called 
carcinoma sarcomatodes. 

The above description applies to the ordinary carcinoma of glandu- 
lar organs. Some difference is observable in the cancers of the skin and 
other external surfaces. In these the structure is rather that of much 
enlarged papillae, the interpapillary epithelial plugs penetrating into the 
deeper tissues. The cells in their early stages are similar to those of the 



PROGRESSIVE TISSUE CHANGES 



235 



deeper layers of the skin, are larger and more translucent than those 
of glandular cancers. Subsequently the cells tend to become of the 
squamous type and undergo more or less horny change. Hollow alveoli 
and acini are unusual in cancers of the skin, though such structures may 
occur in some cases. 

Degenerative Changes. — Carcinomata are quite prone to degenera- 
tions. In nearly all cases in which the tumor has reached considerable 
size more or less fatty degeneration of the cells becomes apparent. 
Preceding this or associated with it may be cloudy swelling or dropsical 
infiltration of the cells, rendering the nuclear outline less distinct and 
sometimes causing vacuolations. Irregular and multiform nuclear de- 
generations are met with, and probably occasion some at least of the 
structures known as parasites of cancer. The epitheliomata of the skin 
are particularly prone to a horny transformation, this occurring first 
and most prominently in the concentric whorls already described. In 
the adenocarcinomata of the ovaries and other genital organs of women 
the degenerated epithelial cells frequently undergo calcareous infil- 
tration, and psammomata are thus formed. Colloid degeneration of 
the epithelial cells is a rare event, and the term " colloid cancer" is gener- 
ally a misnomer, the real degeneration in most of these being myxoma- 
tous, affecting the connective tissue principally, though the epithelial 
cells are to a certain extent involved. Complete degeneration by 
myxomatous or associated myxomatous and fatty change may de- 
stroy all of the characteristics of the original tumor. In some cases 
cystic transformation occurs in organs the seat of cancer, or in the cancer 
itself. This may be due to occlusion and subsequent dilatation of the 
ducts of the organ or of the acini in the tumor, the cystic spaces becom- 
ing filled with mucoid or gelatinous material. In some instances cystic 
carcinomata are secondary developments originating in cystic adeno- 
mata. Hyalin change and pigmentation are rare in cancer. 

Hemorrhage occurs by ulceration of a large vessel. Inflammatory 
processes are quite common. Cancers on free surfaces are prone to 
undergo ulceration in consequence of irritation and infection. Among 
the micro-organisms discovered in such instances the staphylococcus 
and streptococcus are conspicuous. A distinct erysipelatous inflamma- 
tion may occur in cancers as in other structures. Invasion of tubercle 
bacilli and the growth of miliary tubercles in carcinoma are rare events, 
though they sometimes occur. Associations of carcinoma and tubercu- 
losis or syphilis may in other cases result from the secondary growth of 
cancer in pre-existing gummatous or other syphilitic lesions or in lupus. 
Practically all carcinomata show some leukocytic infiltration. The 
amount of this, however, varies greatly. In the healthy tissue border- 
ing carcinomata there is always an inflammatory infiltration of round 
cells, but this does not limit the growth like a capsule. A carcinoma 
is probably never sharply marginated. 

Nature. — Carcinoma is essentially malignant, the degree of malig- 
nancy depending, however, upon the seat and upon certain peculiarities 
of the individual. Sometimes a small growth may remain practically 
latent for a long time, until accidental circumstances, like traumatism, 
intercurrent disease, pregnancy, or the like, stimulate active growth. 



236 



A TEXT-BOOK OF PATHOLOGY 



Its rate of growth is variable, but chiefly it is progressive, regardless of 
speed. Occasionally there are remissions or even cessations, with retro- 
gression and absorption, but this latter is rare. 

Carcinoma exhibits all the elements of malignancy: infiltration, the 
tendency to recur after removal, metastasis, and general deterioration of 
the health. Recurrence after removal is most readily explained upon the 
assumption that the entire growth has not been removed. Microscopical 
studies show that the area of infiltration is usually much greater than the 
naked-eye appearances would indicate, and this explains why the surgeon 
seldom removes the whole disease. Metastasis, as a rule, follows the 
lymphatic channels, and thus primarily involves the lymphatic glands 
in the neighborhood of the growth. 

Pathological Physiology. — The general health of patients suffering 
with carcinoma is affected very profoundly, though the manner in 
which this occurs remains obscure. It would seem to be of the nature 
of a toxemia. (See page. 172). Emaciation and loss of strength are 
habitual, though often, perhaps, in large part the result of interference 
with organic functions, as, for example, in carcinoma of the stomach. 
Progressive anemia may make its appearance, the red corpuscles becom- 
ing less abundant and the quantity of hemoglobin falling decidedly. 
There is usually a moderate amount of leukocytosis, the large mononu- 
clear forms increasing particularly. Toward the end of life the tissue 
destruction increases greatly, though the excretory products of such 
may not be notably increased in the dejecta in consequence of failing 
circulation and imperfect renal function. At this stage the accumula- 
tion of such products in the blood may lead to sudden death from coma. 
(See Acid-intoxication.) For a consideration of the chemistry of cancers 
and their effects see also page 174. Hemorrhages and ulcerations may 
also contribute to the impairment of health in cases of cancer. 

VARIETIES OF CARCINOMA 

There are several forms of cancer sufficiently different to require 
separate description. The classification of these is generally based 
upon the character and arrangement of the epithelium. We may 
distinguish (1) epitheliomata, carcinomata composed of surface epithe- 
lium, either (a) squamous or (6) cylindrical, and (2) glandular carcino- 
mata, having either (a) more or less distinct adenomatous structure or 
(b) solid plugs or columns of epithelial cells, or (c) a mixture of acini 
and solid columns. 

Epithelioma 

This form, which consists of surface epithelium, is of two varieties, 
the squamous and the cylindrical. 

Squamous epithelioma occurs in the skin or mucous membranes, 
where squamous epithelium exists normally. Among the frequent seats 
are the lips, the esophagus, the larynx, and the cervix uteri. Occasionally 
squamous epithelioma arises in parts normally covered by other kinds of 
epithelium, as, for example, in the fundus of the uterus. In these instances 
there is probably a primary metaplasia of the epithelium followed 



PROGRESSIVE TISSUE CHANGES 



237 



by carcinomatous growth. Even in carcinomata of the breast some of the 
acini may present metaplasia of the cells to the squamous type. 

Those forms retaining the cell type seen in the basal layers of the 
rete occur generally over the skin surface while those which undergo dif- 
ferentiation to the prickle cell stage occur chiefly at the mucocutaneous 
junctions. Squamous epitheliomata present themselves as nodular, wart- 
like elevations of the skin or mucous membrane, tending to become ulcer- 
ated on the surface, with little tendency to hemorrhage. Those of the 
mucous surfaces are more elevated and softer. Grossly, on section, they 
appear as firm white or gray masses, with soft areas of cellular growth 
and shiny white striae of connective tissue. Histologically there are seen 
branching columns of epithelial cells extending downward into a stroma, 
well dotted with round cells from the papillae of the skin, into the deeper 
structures. These consist of large translucent squamous cells which show 
a tendency to arrange themselves in 
certain places concentrically to form 
epithelial perles, taking acid dyes well. 
The latter frequently undergo a horny 
transformation and sometimes even 
calcareous change (Fig. 93). The 
same structures occasionally occur in 
papillomata, but much less frequently. 
The characteristic appearance of the 
unrestrained and wholly unnatural 
growth of surface cells is shown in 
Fig. 94. These pearly bodies are 
formed by circumferential pressure 
but aided by the tendency of the cell 
to assume a somewhat spindle shape 
early in its history. It will be noted 
when comparing Figs. 94 and 95 that 
the squamous epithelioma proper is 
made of cells corresponding to the middle outer layers of the epiderm 
while in the basal cell type the cylindrical or cuboidal shape is retained 
throughout. In certain of these tumors there may be, instead of pearly 
bodies, a definite keratinization in strands or balls (Fig. 92); this seems 
rather more common when columnar or cuboidal cells undergo metaplasia. 
Metastasis is frequently seen in the neighboring lymphatic glands, but 
the malignancy is less marked than in glandular carcinomata. 

Some authors have described as a separate form skin cancers com- 
posed of cuboid or polymorphous cells resembling those of the basal layer 
(Malpighian layer) of the skin, that is the formative epithelial elements 
carcinoma basocellulare. While in typical squamous epithelioma, 
differentiation proceeds to the prickle cell stage, in this tumor no metamor- 
phosis occurs, the rete cells developing downward in a manner seemingly 
disconnecting them with the superficial layers and retaining their cuboidal 
shape with no prickly bridge between neighboring cells. The cell groups 
are sharply outlined in acinar arrangement and do not show the disorderly 
digitation of epithelioma. Such nepolasms appear most commonly on 
the face, especially about the eyes and nose but are also seen on the trunk 




Fig. 93. — Squamous epithelioma, 
showing whorls of epithelial cells with 
central degeneration (from a photograph 
by Dr. W. M. Gray). 



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A TEXT-BOOK OF PATHOLOGY 



appearing as a reddish warty area at first, slowly ulcerating and sluggishly 
spreading but usually progressive and frequently leading to disfigure- 
ment such as loss of the alse of the nose or parts of the eyelid. On 
section one notes that they are at first covered with epidermis, and 
are rather strictly limited to the corium as gray, red or whitish 
nodules or masses and not evidencing irregular infiltration; 
moderately active inflammation accompanies their ulceration. They are 




Fig. 94. — Squamous epithelioma showing digitation of cellular strands, various stages of 
pearl formation and the cellular fibrous supporting tissue. 

usually benign, the local destructive tendency being the only evidence of 
malignancy. These tumors arise either from the simple basal cells or 
those of the skin glands; certain writers would have it that they all arise 
from glands but this is probably not the case. 

Other varieties of epithelioma have been described depending upon 
the shape, arrangement, and alteration in the cell-nests. The cystic epi- 
thelioma is of the basal cell type, with degeneration of cell-nests and the 
formation of cysts. The trichoepithelioma, another basal cell tumor, is 
thought by some to be derived from hair follicle and to show branching 
and communicating, sharply outlined nests. The name " epidermoid 
carinoma" is given to those infiltrating growths which retain the strati- 



PROGRESSIVE TISSUE CHANGES 



239 




Fig. 96. — Cylindrical epithelioma of the intestine (Perls). 



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A TEXT-BOOK OF PATHOLOGY 



fication of the epidermal layers, or which assume this arrangement when 
not ggowing from epidermis. 

During the growth of the epithelioma, the adjacent superficial cells are 
irritated in some way and respond by multiplication. There is thus formed 
a thickening of the epidermis, accommodated in two directions, outward 
and inward, the former being seen grossly as a roughened, overgrown or 
warty edge, microscopically as a widening of the horny layer; the latter, 
only seen on section, being a rather orderly penetration of the corium by 
hand-like projections of the lower epidermal layers. All through this 
reaction the proper adult tissue relations are attempted and it is not to 
be looked upon as part of the neoplasm. 

Cylindrical Epithelioma. — This form is composed of columnar 
or cylindrical epithelium. It is frequent in the mucous membranes, 
especially in the gastro-intestinal tract and the uterus. The epi- 
thelial cells of the tubular glands or sometimes those of the surfaces 
form the starting-point of the growth. More or less acinus-like tubular 
structures, composed of a layer of epithelial cells, or more frequently 
of a number of layers of epithelia, the outer layer being often distinctly 
columnar, constitute the characteristic feature of the tumor (Fig. 96). 
In the later stages the acini become filled with proliferated epithelial 
cells of various shapes and the cylindrical or tubular character of the 
lining is lost. Carcinomata of the kidney, liver, and mammary gland, 
though not originating from surface epithelium, strickly speaking, may 
be of the cylindrical form. Cylindrical epitheliomata more nearly re- 
semble the glandular carcinomata in their malignancy and general be- 
havior than the squamous variety. 

Glandular Carcinoma 

This term includes the carcinomata that have a resemblance to 
racemose glands in their histological structure. They consist of acini or 
alveoli containing epithelial cells, usually in several layers or completely 
filling the lumen, and a stroma of connective tissue. Some authors 
distinguish three forms : the simple, the medullary or encephaloid, and the 
scirrhous. These are simply variations of the same tumor. In the simple 
form there is a combination of epithelium and stroma in about the propor- 
tion seen in normal glands. The tumor is, therefore, neither strikingly 
hard nor soft. In the medullary or soft carcinoma the amount of epithe- 
lium is excessive and the tumor has a soft character (Fig. 97) ; while the 
scirrhous, or hard, cancer is an indurated form, due to excess of fibrous 
tissue and deficiency of the epithelium (Fig. 98). 

The glandular cancers are more or less nodular or infiltrating growths, 
varying in consistency in different cases, but having, on section, a glisten- 
ing white color with a certain amount of translucency. Milky liquid 
exudes from the surface on section. This is composed of albuminous 
fluid containing degenerated epithelium and free oil-droplets. Among 
the seats in which these forms occur the most important are the pylorus 
and other mucous surfaces, the mammary gland, the pancreas, kidneys, 
ovaries, and testicles. Widespread metastasis and other features of 
malignancy are noted. In the case of the scirrhous form the primary 



PROGRESSIVE TISSUE CHANGES 



241 




16 



Fig. 98. — Scirrhous cancer of breast (Warren). 



242 



A TEXT-BOOK OF PATHOLOGY 



tumor may be strikingly small in comparison with the amount of metas- 
tatic deposit. We may further divide glandular cancers according to 
the source from which they arise or as to the general architecture they 
retain during the earlier stages. Thus we may speak of (1) columnar 
epithelial carcinoma when throughout the formative stages the long 
narrow cells are retained. These grow from tubular glands with cylin- 
drical epithelium like in the intestinal tract. (2) Duct cancer when 
cuboidal cells predominate and the general arrangement is tubular. 
(3) Acinous cancer when the acinus grouping, with more or less distinct 
cell-nests having a low or polymorphous epithelium, predominates. 

Special Forms of Cancer 

There are degenerations in some cancers which give them peculiar 
physical and chemical properties. Such alterations do not justify a 
pathological separation, but clinically 
they have an importance. The 
most important are mucoid and col- 
loid. In the former the interstitial 
tissue undergoes myxomatous change, 
making the tumor soft and distended 
with a viscid material. In colloid 
cancer the cells undergo the change. 





Fig. 99. — Colloid cancer of the breast, 

showing myxomatous change in the stroma 

and fatty degeneration and partial disap- 
pearance of the epithelial cells (Perls). 



Fig. 100. — Colloid cancer of the 
peritoneum (modified from Birch- 
Hirschfeld) . 



The term "colloid" is usually a misnomer, as most of the colloid 
cancers contain no colloid material. The name gelatinous would be 
more appropriate, but has not been generally accepted. Such colloid can- 
cers are met with in the stomach and intestinal tract, in the mammary 
gland, and in the ovaries. The tumor has a peculiar transparent, glis- 
tening appearance. The entire mass may be uniformly jelly-like or 
only portions of it are affected. Microscopically mucoid degeneration of 
the epithelial cells and stroma is discovered (Fig. 99). In some cases'no 
trace of carcinomatous tissue may be discoverable, the whole tumor 
having undergone degeneration. Degenerative cancers frequently spread 
by direct extension, and the entire abdominal cavity may become filled 
with material representing degenerated secondary growths. Occasion- 



PROGKESSIVE TISSUE CHANGES 



243 



ally the same kind of peritoneal growths seem to originate primarily 
in the peritoneum; the origin of these may be fetal remnants of epi- 
thelial tissue (Fig. 100). 

True colloid cancer — that is, carcinoma with colloid degeneration 
of the epithelium — is sometimes seen, though it is very rare. It oc- 
casionally causes a gross appearance resembling that of sarcomatous 
cylindroma, and the term carcinomatous cylindroma has been applied. 

CYSTS 

Definition. — This term includes pathological formations of varied 
character. Some are true tumors; others are of quite different nature. 

The term "cyst" is applied to pathological formations consisting of 
a more or less well-defined wall and enclosing liquid or semiliquid con- 
tents of different character from the surrounding parts. This definition 
is not entirely applicable, as certain structures that do not present a 
definite capsule are sometimes termed "cysts." Accordingly, we may dis- 
tinguish between true cysts and cyst-like formations or cystoids, the for- 
mer being enclosed by a capsule lined with epithelium or endothelium; 
the latter merely presenting a circumscribed collection of softened 
material. 

Classification. — According to the method of formation, we dis- 
tinguish retention cysts, softening cysts, cysts due to the presence of 
foreign bodies, and proliferation cysts. There are also cysts which 
owe their origin to some faulty development in utero. They are in a 
sense teratomatous and we shall consider them under a separate heading. 

Retention cysts are formed when the excretory ducts of a gland 
become occluded and the secretions accumulate and cause distention 
of the acini or of parts of the duct. Among such cysts may be named 
the distended sebaceous glands of the skin in the formations called 
wens; the cysts of the salivary or small mucous glands or ducts under 
the tongue, called ranulce; retention cysts formed in the uriniferous 
tubules, the tubules of the ovary, or in the parovarium, in the acini and 
ducts of the mammae, pancreas, and other glands. An entire organ 
may become converted into a cyst, as in cases of distention of the kidney 
(hydronephrosis) from obstruction of the ureter. 

These cysts are distinguished by the fact that they have a distinct 
connective-tissue wall lined with epithelium or endothelium. The 
accumulation in such cases is due to a continuation of secretory activity 
with no release of its product, so that such parts as water and.cystalloids 
are reabsorbed and the remainder exists usually as a thick gelatinous 
mass. While the pressure of the contents is not great, epithelial and 
connective tissue activity continues with other productions of over- 
growth but when distention becomes excessive, epithelia are flattened 
and septa become thin. 

Cysts of this order may arise in endothelial tissues such as in hydrocele 
of the scrotum or in bursal accumulations. These are doubtless due to 
some inflammatory change in the wall preventing lymph absorption. 

Softening cysts occur in consequence of degenerative softening of 
normal or pathological tissues. They are not rarely the result of hemor- 



244 



A TEXT-BOOK OF PATHOLOGY 



rhage, the blood-clot first becoming inspissated and then serous exuda- 
tion occurring in the area of hemorrhage. Softening cysts are very 
common in tumors of different kinds. 1 

Cysts due to foreign bodies are, in part, softening cysts. The tissues 
in the immediate vicinity may be injured and undergo necrotic soften- 
ing, while connective-tissue reaction produces a capsule. This form of 
cyst is most frequently the result of invasion of parasites, and the cyst 
contents may be composed of the parasite or the parasite and tissue 
elements more or less degenerated. 

Proliferation Cysts. — This term is applied to formations more closely 
analogous to true tumors than those mentioned before. They 
merit more extended description than the other forms of cysts, and may 
be designated as epithelial cysts. 

Epithelial Cysts 

Definition. — In certain glandular organs, notably the ovary and 
mammary gland, cystic formations occur which present certain individ- 
uality, and, though perhaps they represent adenomatous or carcinomatous 
new growths, are so striking as to deserve special mention. 




Fig. 101. — Papilliferous adenocystoma of the kidney (Karg and Schmorl). 

Etiology. — These growths, in part at least, result from obstruction 
of excretory ducts and subsequent irritation by retained secretions. 
Congenital abnormalities of structure may possibly play a part in their 
causation. Traumatic displacement of surface epithelium into sub- 
epidermal layers is thought to be the cause of certain small cysts of the 
skin, mucous membranes and conjunctiva. In this locality tissue 
fluids accumulate and perhaps the misplaced cells exert some secretory 
power. 

Appearance. — Cystomata may be single or multiple, the entire 
tumor being composed either of a single cyst or of one large cyst sub- 
divided into many smaller ones; or, again, of numerous separate and un- 
connected cysts of varying size. On section, the cystic cavities are found 
to contain more or less serous or gelatinous liquid, and sometimes hemor- 



PROGRESSIVE TISSUE CHANGES 



245 



rhagic fluid is observed. Most frequently the liquid is gelatinous or 
ropy, and is commonly spoken of as colloid material. The inner lining 
of the cyst may be smooth, like a serous or mucous surface, or elevated 
irregularly in the form of polypoid outgrowths into the cavity of the 
cyst. The entire cyst may thus be filled with papillomatous elevations 
from the epithelial lining. The term papuliferous or proliferative cysto- 
mata is given to these forms (Fig. 101). The size of cystomata varies 
from minute tumors not larger than a pea to enormous masses weighing 
as much as 60 or 80 pounds. Secondary degenerations may occur 
in the form of softening, hemorrhage, or calcification. 

Seats. — The mammary gland and ovary are the principal situations 
in which tumors of this description are met with, but analogous growths 
may make their appearance in any of the glandular organs. 

Structure. — Microscopically, these growths present cystic cavities 
lined with typical or modified columnar epithelium and a stroma or 
reticulum of connective tissue. The amount of the latter and the ap- 
pearance of the cysts themselves vary in different cases. At times 
the stroma is very abundant and takes the form of well-organized fibrous 
tissue, while the cysts and acini are small and few in number. In these 
cases the appearance suggests a primary proliferative connective-tissue 
process with secondary implication of the epithelial elements. Such 
cases occur particularly in the mammary gland, and there is difficulty 
in separating them sharply from instances of chronic interstitial mastitis 
or diffuse fibroma. In other instances the process manifestly begins 
with the formations of epithelial acini, and the hyperplasia of the con- 
nective tissue is certainly secondary. The acini in these cases present 
themselves as hollow spaces of varying shape and size, often branching, 
and lined with columnar epithelium in a single layer or sometimes with 
several layers of more or less well differentiated columnar epithelium, thus 
simulating adenoma from which some cases undoubtedly originate. 

Nature. — These cystic growths often have a decided tendency to 
malignancy. They may remain benign throughout; but frequently 
they undergo carcinomatous change and spread widely or give rise to 
metastasis. The malignancy is generally in proportion to the amount of 
the epithelial proliferation and papuliferous change, but there are in- 
stances in which metastasis occurs from adenocystomata having regular 
gland acini lined with single layers of typical columnar cells. The cysto- 
mata of the ovary not rarely extend to the surface of the organ, break 
through the capsule, and present upon the surface as papillary growths, 
and frequently they extend to the peritoneum and neighboring struc- 
tures. The entire abdomen may be involved. At the. same time, or in 
other cases independent of such direct extension, metastatic deposits 
may be seen in nearby lymphatic glands. Somewhat the same conditions 
may be observed in cystoma of the breast, but in this situation the tumor 
is much more frequently confined within the capsule of the organ. 



CHAPTER VII 



TERATOLOGY 

This subject includes all those abnormalities which are due to con- 
genital defect. Such a subject while not exactly a part of the progres- 
sive tissue change, is ushered in here by the necessity of taking up 
certain tumors having a polymorphous character more or less dependent 
upon formative defects. Teratomata or mixed or polymorphous tumors 
or those due to formative defect will first be considered, and the terata 
will then be discussed. The word "terata" may be applied to any ab- 
normalities of growth, but is best confined to monsters. In order to 
show the position of the various abnormalities we here give a short 
classification (Birnbaum's), which also indicates in a measure what we 
know of the etiology: 

(a) Single monsters. 

(1) Malformations due to arrest of development. 

(2) Malformations due to excess of development. 

(3) Malformations due to errors of development. 

(4) Malformations due to displacement of tissue and per- 

sistence of fetal structures. 

(5) Malformations due to fusion of several characters. 

(b) Double monsters. 

Two theories are given for monster formation. One is that there is 
some inherent fault in the germinal cell, and the other ascribes mal- 
formation to malign influences upon the developing ovum. The latter 
is more generally accepted. It is assumed that the damage is chiefly 
felt before the gastrula stage in a single ovum. 

Since all organs or organ systems do not progress to their develop- 
ment in a regular progression, but in an irregular saltatory manner, the 
correct development of any one depends upon the proper mutual relations 
of adjacent or associated units or groups. If, therefore, the progress and 
restraint of one unit be removed, this allows abnormal growth in those 
dependent upon it. In this way one can explain headings a, 1-3, 5; 
while the double monsters are expressions of the above effects upon a 
doubly impregnated ovum. Twins can arise from one ovum. 

TERATOMATA 

Definition. — The term " teratomata" is applied to tumors of peculiar 
mixed character, representing different elements of complex tissues 
or structures in a situation in which these do not normally occur, growing 
typically, atypically, or both. For example, the most frequent form of 
teratoma contains various epidermal structures, such as hair, teeth, 
etc., and occurs in internal organs. Those containing fetal tissue or 
abnormally placed tissue come under heading a, 4. 

246 



TERATOLOGY 



247 



Etiology. — The causation of teratoid tumors or teratomata is to 
be sought in congenital misdevelopments. We may, with Klebs, dis- 
tinguish endogenous forms in which inclusions of superficial tissues are 
retained in internal parts by a process of constriction; and ectogenous 
forms, in which a separate fetal deposition is the origin of the tumor. 
The latter form represents a separate and ill-developed fetus within 
the developed organism — a fetus in fetu. They are also called "em- 
bryomata." A regular gradation may be traced from distinct teratoid 
tumors having irregular mingling of tissue elements to malformations 
in which a more or less systematic outgrowth, somewhat approaching 
double monstrosities, occurs. Of the distinct teratoid tumors, the most 
frequent is the dermoid cyst. 



Fig. 102. — Dermoid cyst of the lung. (From the Vienna General Hospital Collection.) 



This ectogenous tumor presents itself as a cystic formation with a 
connective- tissue membrane and an inner lining resembling the skin. 
This may present all the elements of the skin, such as stratified epi- 
dermis, a papillary layer, and even subcutaneous connective tissue. 
Hair-follicles and sebaceous glands are frequent, and habitually long, 
light-colored hairs are found within the contents, and teeth may be 
found in the lining membrane or free in the contents of the cyst. The 
cyst is filled with a semifluid, cheesy mass consisting of epithelial cells, 
fatty matter, and other detritus. Occasionally dermoid cysts may 
contain nerve tissue, muscle, thyroid tissue, or structures resembling 
intestine. 

The dermoid cysts vary in size from minute bodies no larger than a 
pea to huge masses, the latter being most frequent in the ovaries. Among 
the situations in which dermoids occur the ovaries are most common; 
less frequently they are found in the testicles, in the peritoneum, in the 




DERMOID CYST 



248 



A TEXT-BOOK OF PATHOLOGY 



membranes of the brain, about the eye, in the neck, floor of the mouth, 
and elsewhere. Growth is very slow, and they may remain practically 
latent through life. 

The nature of these tumors is usually benign, though carcinomatous 
change may occur, and in the ovaries cystoma is prone to be associated, 
and the latter may be malignant. 

Other Teratoid Tumors 

Mixed tumors are terata arising from embryonal cells which are 
capable of a differentiation to approximate more than one type of adult 
tissue. They may descend from cells of one or all layers of the embryo, 
and may be ascribed to the power of syncytial cells to develop into an 
embrj^o, or the inclusion of one ovum in another. These are the tera- 
tomata proper, to which reference has been made, while mixed tumors 




Fig. 103. — Mixed tumor of thyroid gland. 



represent usually two or, at most, three types of cells. The most con- 
spicuous examples are Wilm's congenital adenosarcoma of the kidney 
and adrenal carcinoma. From this it will be seen that the term mixed 
tumors as used here does not imply such mixtures as adenoma and carci- 
noma, chondroma and myxoma, in which the combination is probably in the 
nature of metaplasia, but on the other hand covers those growths em- 
bracing tissues of different embryonal origin whether it has undergone its 
normal metamorphosis or not. The latter variety is most frequently 
seen in sex and salivary glands. The structure of these malformations 
differs widely and at times one can scarcely establish the nature of all the 
tissues. As shown in the illustration (Fig. 103) one sees nests like sarcoma 
and carcinoma side-by side with cartilage. There has been much dis- 



TERATOLOGY 



249 



cussion as to the exact nature of the cells in many of these tumors but 
because metastasis occurs so often via the blood vessels some observers 
profess to believe them sarcomatous. 

Nodular masses may appear about the head or neck or in various 
parts of the body, consisting of mingled tissues of various kinds, such 
as glandular tissues, connective tissues, nerve, muscle, etc. Sometimes 
they resemble some definite organ, as in the case of growths appearing 
at the umbilicus of the newborn and simulating the structure of normal 
intestine. 

In the neck there are sometimes seen more or less cystic growths 
lined with epithelium and having in their walls muscle-fibers, lymphoid 
tissue, cartilage, etc. These growths probably spring from remnants 
of the embryonal branchial clefts. The mixed tumors of the parotid 
gland (see Sarcoma) are allied to these. 




Fig. 104. — Cholesteatoma from the membranes of the brain. 



Cholesteatoma. — This tumor is characterized by glistening, whitish, 
or pearly bodies composed of concentric layers of cells resmbling epi- 
thelium (Fig. 104). Sometimes crystals of cholesterin are found in the 
center of these bodies, whence the name cholesteatoma. Cholesteato- 
mata are found in the membranes or substance of the brain, and present 
themselves as single or multiple nodules. They are usually soft and 
glistening in appearance. Some authors consider them endotheliomata, 
but Ziegler has found hair-follicles and hairs in certain specimens, 
and from this, as well as from the horny change to which the cell 
in the pearly bodies are prone, classifies them among the teratoid 
growths. They probably originate in ectodermal fetal inclusions or 
rests. 

Somewhat similar tumors occur in the pelvis of the kidneys, in the 
testicles, parotid glands, ovaries, and middle or external ear. 



250 



A TEXT-BOOK OF PATHOLOGY 



SYNCYTIOMA MALIGNUM 

This term is applied to a form of tumor origgnating at the placental 
site during pregnancy or the puerperium. It has also been called 
"deciduoma maliqnum" 11 sarcoma deciduocellulare, " " destructive 
epithelial tumor of the placental site," and ' ' chorionepithelioma" 
(Fig. 105). It may follow a hydatid mole (q. v.). 

The tumor occurs usually at the placental site, sometimes as a poly- 
poid mass in the uterine cavity but more often as a soft hemorrhagic 
infiltrating growth, somewhat resembling placental tissue in gross appear- 
ance, and frequently causes metastasis by breaking into the blood-vessels. 
The metastatic nodules are found in the external genitalia, frequently in 
the lungs, less often in the liver, spleen, or other organs. The growth is 




Fig. 105. — Chorionepithelioma or syncytioma malignum. (By the courtesy of Dr. Barton k 
Cooke Hirst from a painting made for him from a slide belonging to Dr. Herbert Fox.) 

rapid, the uterine wall being quickly invaded and metastasis occurring in a 
short time. It has no vessels, but grows within placental blood spaces, 
and is prone to hemorrhage by infiltration and ulceration of maternal 
vessels. The cells are loosely enough arranged to separate and enter 
vessels to form metastasis. 

The nature of this tumor is still the subject of some controversy. 
Two types of cellular elements are recognized in its structure. One 
of these consists of irregular masses of protoplasm containing dark 
nuclei (syncytial tissue). The nuclei probably multiply by direct divi- 
sion. These protoplasmic masses are arranged in islands or in branch- 
ing columns which form a network. In the meshes of this network 
are blood spaces containing thrombi or masses of blood corpuscles. 
Sometimes masses like those above described are found within the 
blood spaces. The second form of cells consists of smaller irregular- 



TERATOLOGY 



251 



shaped elements, which are unusually rich in glycogen, and in which 
cell division by karyokinesis is observed. These cells lie in masses, of 
greater or less size, between and beside the larger protoplasmic areas 
before described. In the later stages of the growth obliterative throm- 
bosis of the vessels leads to necrosis of the cellular constituents, particu- 
larly of the columns of large epithelium-like cells. These are converted 
into homogeneous fibrinous masses, and even the thrombi themselves 
may degenerate. The view of Marchand regarding the nature of these 
tumors is most widely accepted. He holds that the larger cells are deriva- 
tives of the syncytium (a structure composed of epithelial cells, probably 
of fetal origin), while the smaller cells are formed from the deeper 
epithelial covering of the chorion villi (Langhans' cells). The tumor, 
therefore, is epithelial in nature, and it has malignant properties. It 
differs, however, from ordinary epithelioma and from carcinoma in its 
peculiar structure and in its clinical course and dissemination. 

Syncytial cells are occasionally found in tumors of the adult unasso- 
ciated with pregnancy. Such syncytia doubtless arise at times from the 
fusion of many cells but they are frequently enough encountered in 
combination with elements whose origin suggests displacement of em- 
bryonal tissue and in such mixed tumors as are common in the testicle, 
that it would seem fair to consider them as remnants derived from the 
fetal membranes, a fetus in fetu. Curiously enough those tumors and 
their metastases may be polypoid or hemorrhagic and infiltrating like 
the placental form. They are most often seen in the testis and brain. 

Terata or Monsters 

We refer the student to books on normal and abnormal embryology 
and teratology for a full discussion of the terata. Here will be given 
only examples of the various headings on p. 246: 

(a) Single Monsters. — (1) Malformations by arrest of development 
are exemplified by the failure of closure of the median fissure of the body 
or the failure of union of organs developing in both sides and intended 
to be one, e. g., the bifid uterus, harelip. 

(2) Malformation in excessive development occurs in the form of 
supernumerary fingers or internal organs, the spleen, for example. 

(3) Malformations of errror are seen in club-feet, hernia, or when 
the testicle is not included in the scrotum. Hermaphroditism exem- 
plifies failure of fusion of sexual elements from the two sides. 

(4) Malformation by displacement is exemplified by transposition 
of all the viscera (situs transversus) or of single organs, as when 
the heart is found on the right side. Persistence of a remnant of the 
omphalomesenteric duct, so-called Meckel's diverticulum, and of the 
truncus arteriosus are instances of the retention of embryonal structures. 

(5) Under this heading are found fusion of esophagus and trachea, 
and of the two kidneys, forming a horse shoe shaped organ. 

(6) Double monsters are the results of superfetation, or the fusion 
of incompletely formed fetuses. When the two fetuses are joined 
together by the ventral surface they are called anterior duplications; 
when joined by the head, craniopagus; by the sacral region, pygopagus. 



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When they are fused at the pelvis they are ischiopagi; and if the trunk 
and legs are fused, leaving the head and neck free, we have dicephalus. 
Syncephalus means fusion of heads with the two bodies free. 

The cysts of antenatal origin are mostly examples of endogenous, 
constriction, or inclusion cysts, or remains of fetal structures intended 
for removal. The thyrolingual cyst is due to failure of closure and 
obliteration of the thyrolingual duct. It is in the midline of the neck. 
Branchial cysts at the side of the neck are mucous or sebaceous collec- 
tions in the remains of the branchial clefts. Persistent portions of the 
Wolffian body or duct may give rise to uni- or multilocular cysts of the 
ovary or broad ligament. Cysts of the kidney are due to imperfect 
development of the portion of the Wolffian body which makes the 
secreting part of the kidney. 



CHAPTER VIII 



BACTERIA, THEIR NATURE AND ACTION 

History.- — -Although for many centuries there had existed the 
idea that disease and decay are due to the action of minute organisms, 
it was not until the use of the lens enabled the Dutch naturalist Leeuwen- 
hoeck actually to demonstrate their presence in water and in human 
intestinal contents that the hypothesis of a "contagium vivum" became 
more than mere guesswork. He discovered, even with his imperfect 
instruments, short rods, curved and straight, and described their 
motility. Miiller (1785), by the use of the compound microscope, at 
■tempted a more systematic classification of these micro-organisms, and 
from that time many investigators have added much to our knowledge 
of microbes, -that group of organisms which had been denominated by 
Linnaeus by the term " chaos. " To the German Henle is due the credit of 
having first introduced an idea of order into this disorder. He held that 
fermentation was the result of organic life, and that the action of a 
contagium was analogous to that of a ferment. The earliest systematic * 
experimental work was that of Pasteur, in which he established beyond 
doubt this relation between fermentation and the life and development 
of bacteria. The first definite ideas of the physiology of these micro- 
organisms are found in his experiments on lactic-acid fermentation, 
and the pathogenesis of micro-organisms was established by his demon- 
stration of the etiology of the silkworm disease (1869). Davaine and 
Rayer about the same time established the causal relation of a bacillus 
found in the blood of a sheep dead of anthrax to that disease. 

CLASSIFICATION 

Bacteria (schizomycetes, or cleft fungi) is the name given to a 
branch of the lowest and simplest of the orders of the vegetable kingdom. 
They belong to the class Thallophyta and order Schizophyta or Schizomy- 
cetes. Other orders of this class are unimportant except the Eumycetes, 
comprising the moulds and yeasts. They are small, unicellular organ- 
isms, generally free of chlorophyl, and colorless; they possess a cell- 
membrane albuminoid in composition, and homogeneous protoplasmic 
cell contents. They range in size from a fraction of a micromillimeter 
up to 40 ix. Some varieties are motile. Nuclei are absent, though 
in the opinion of some the whole body may be regarded as a nucleus. 
Bacteria multiply by cell division, sexual distinctions being absent, 
In many species resistant bodies — spores — occur. 

253 



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A TEXT-BOOK OF PATHOLOGY 



Many classifications, all of them being to a certain extent artificial 
have been made by different authors. Probably one of the most use- 
ful and scientific is that of Migula, as modified by Chester: 

Schizomycetes 

I. Coccaceae. — Spherical cells dividing in one, two, or three directions. Endospores 
rare. 

1. Streptococcus. — Division in one direction, the individuals cohering to form 

chains. Motility absent. 

2. Micrococcus. — Division in two directions, the individuals when coherent 

forming groups of four. Flagella absent. 

3. Sarcina. — Division in three directions, forming packets of eight, increas- 

ing in geometrical ratio. Motility absent. 

4. Planococcus. — Division in two directions, as in the micrococcus. Motility 

present. 

5. Planosarcina. — As the sarcina. Motility present. 

II. Bacteriaceae.— Rod-like, cylindrical cells, dividing at right angles to the long 
axis. 

1. Bacterium. — Cells without flagella, often with spores. 

2. Bacillus. — Cells with peritrichous flagella, often with spores. 

3. Pseudomonas. — Cells with polar flagella, spores rare. 

III. Spirillaceae. — Cells cylindrical, curved, bent, or spiral. Division as in II. 

1. Spirosoma. — Cells rigid, without flagella. 

2. Microspira. — Cells rigid, with one, rarely two or three, polar flagella. 

3. Spirillum.. — Cells rigid, with five to twenty polar flagella. 

4. Spirocheta. — Cells flexible, motile, but without flagella; perhaps possessing 
an undulating membrane. 

IV. Chlamydobacteriaceae. — Cells united in a simple unbranched filament. Division 

in one direction. Forms non-motile; conidia. 

1. Mycobacteriacece. — Short or long cylindrical units or filaments, clavate, cuneate, 

irregular, or regular in form; may have false or true branching. No spores. 
Gonidia bodies may occur; non-motile; transverse division; no sheath. 

a. Mycobacterium. — Short cylindrical, bent cuneate. May show true 

branching. 

b. Actinomyces. — Long branching filaments, gonidia, end organs, dry 

growth (very close to next genus, Streptothrix). 

2. Streptothrix. — Cells united in a simple unbranched filament. Division in 

one direction. Forms non-motile; conidia, true branching. 

3. Cladothrix. — Cells united in a filament, with a false branching. 

4. Crenothrix. — Cells united in an unbranched filament, and dividing in three 

directions into small rounded cells. 

5. Phragmodiothrix. — Cells at first united in an unbranched filament, and dividing 

in three directions. Later the separate cells break through the thin mem- 
brane and grow out as branches. 

6. Thiothrix. — Cells united in an unbranched filament contained in a thin mem- 

brane. Division in one direction. Cells contain granules of sulphur. 
V. Beggiatoaceae — Cells united in a filament without sheath. Motile, the move- 
ment being due to an undulating membrane. 

Eumycetes 

True fungi are of some pathological importance in skin diseases and occasion- 
ally in general infections. The classification is given of the most important genera. 
This is one of the orders of the Thallophyta. 

1. Suborder Phycomycetes. 

Family Mucorinae, Genus Mucor. 

2. Suborder Hemiascomycetes. 

Family Saccharomycetacece, Genus Saccharomyces, Subgenus Blastomyces. 

3. Suborder Euascomycetes. 

Family Aspergillacese, Genus Aspergillus, Genus Penicillium Genus Oidium. 



BACTERIA, THEIR NATURE AND ACTION 



255 



The simple elementary forms that occur are of three kinds: the 
coccus, the bacillus, and the spirillum (Fig. 106). 

Coccus. — This is a spherical cell, varying in size up to 1 /x in diam- 
eter. It takes the anilin stains readily. Spore formation and motility are 
rare. When the cocci are found in groups, the individuals being entirely 
separate, they are termed staphylococci, from the resemblance of the 
groups to a bunch of grapes; when in pairs, diplococci; when in chains, 
streptococci; when in groups of four, tetrads, or merismopedia; when in 
packets, sarcinse. 



i * 3 4 5 6 7 8 9 ' to ii 

Fig. 106. — Various forms of bacteria: 1 and 2, Round and oval micrococci; 3, diplo- 
cocci; 4, tetracocci, or tetrads; 5, streptococci; 6, bacilli; 7, bacilli in chains, the lower 
showing spore formation; 8, bacilli showing spores, forming drumsticks and Clostridia; 
9 and 10, spirilla; 11, spirochetes. 

Bacillus. — A rod-shaped, cylindrical cell of varying length and thick- 
ness. Spore formation and motility are common. Most of the group 
stain easily with the anilin dyes, but some require special methods of 
staining. 

Spirillum.— A cylindrical, rod-shaped cell, curved or spiral, some- 
times motile. It stains readily. 

MORPHOLOGY 

Cell Contents. — The body of the organism in unstained conditions 
appears as a perfectly homogeneous protoplasmic mass. On staining 
with anilin dyes a granular appearance is often observed, which under 
high powers is resolved into a hyaline mass containing numerous 
chromophilic granules. Vacuolations also are often present. Some 
observers (Butschli et al.) have made out a network immediately 
within the membrane and surrounding a central body which readily 
stains with the nuclear dyes. This latter they regard as a nucleus. 
Others, however, affirm that this appearance is due to a concentration 
of the cell protoplasm (endoplasm), the result of the rather complicated 
method of staining. The question of the presence or absence of a nucleus 
is still an open one. In many organisms, as the diphtheria bacillus from 
a blood-serum culture, for example, there exist certain transparent re- 
fractive bodies which stain differently from the rest of the microbe. 
These metachromatic bodies, as they are called, are regarded by Ernst 
as nuclear in character, and observations in our laboratory would seem 
to ascribe to them a place in reproduction and regeneration. 

Most authorities today merely accept that a bacterium has both 
chromatic and cytoplasmic parts, and do not insist that the large central 
area staining by nuclear methods is a definite nucleus. Some of the 
chromatic bodies seem to have the power of growing out into a full 
rod when freed from the parent rod into favorable media (Kneass). 

Spore. — The spore is a non-vegetative resistant form that the microbe 
assumes when the conditions for growth are unfavorable. The endo- 



256 



A TEXT-BOOK OF PATHOLOGY 



plasm seems to concentrate and become a s.mall oval, highly refractive 
body, separated from the bacterial protoplasm by a membrane of its 
own. It is generally of the same diameter or somewhat smaller than 
the bacillus itself, and is situated either in the middle (equatorial) or 
at the end of the microbe (polar spore). It may be larger in diameter 
than the microbe and cause a swelling at that point. When in the center 
of the rod this gives rise to the form known as Clostridium; when polar, 
to the so-called drumstick form (as in the Bacillus tetani) . 

The spore is extremely resistant to conditions to which the vegeta- 
tive form readily succumbs; to the action of certain chemical reagents, 
light, heat, etc. Bacteria that are grown on media poor in nutrient 
material tend to become asporogenous. A certain temperature is also 
necessary for spore formation. Thus, although the anthrax bacillus 
develops well at a temperature of 14° C. (57° F.), it does not form 
spores below 18° C. (64° F.). To obligate anaerobes oxygen is necessary 
for their development, and aerobic cultures present them in the ab- 
sence of that gas. Placed under conditions favorable to its vegetation 
the spore loses its clearness, absorbs water, and swells. A small promi- 
nence presents at the side or end, which gradually lengthens and develops 
into a young bacillus. The membrane of this new microbe is formed 
from the inner layer of the spore membrane [endosporium) , while the. 
outer layer (exosporium) is cast off. In not all of the varieties of bacilli 
does sporulation take place, and even where it does occur there may, 
under certain conditions, as in growth at high temperatures, arise races 
which have lost this power (asporogenous races). 

The spore does not stain readily with the ordinary anilin stains, 
and special methods have been devised for coloring it. 

The polar or Babes-Ernst granules are condensations of endoplasm 
which stain by particular methods. They are due to the chemical 
reactions of the medium upon which the organisms are growing. Their 
biological importance is small, but they assist in identification at times. 

Cell=membrane. — Surrounding each organism . is a membrane 
(ectoplasm) denser and more highly refractive than the cell contents 
(endoplasm). In most cases this is not to be differentiated from the 
endoplasm; but in a few it is larger, and under certain conditions be- 
comes a gelatinous mass. In this case it is easily seen, especially after 
appropriate staining. This is called the capsule. In general, this occurs 
only when the bacteria develop within the animal organism, and not 
upon artificial culture-media. It is probable that the ectoplasm is not 
a mere protective envelope, but has to do with the functional activity of 
the bacterium. The fact that the flagella, to which is due the motility 
of certain microbes, are directly continuous with and are simply pro- 
longations of this membrane, points to this view. 

The cell-membrane is not easily colored by ordinary methods. 

Flagella. — Motility is often a property of bacteria. It is manifested 
in different ways, and is often characteristic of special varieties of bac- 
teria. Some move slowly forward across the field; others, with great 
rapidity; others, again, dart hither and thither, slowly or so quickly as to 
be with difficulty observed. They may at the same time have a rotary 
movement around their long or their short axes. 



BACTERIA, THEIR NATURE AND ACTION 



257 



• After appropriate staining the cause of this motility is seen to be the 
presence of slender, whip-like prolongations, originating directly from 
the ectoplasm (Babes). They may be twenty times as long as the body 
of the bacterium, and are arranged in the different species in different 
ways. Bacteria that possess no flagella are termed "gymnobacteria" ; 
those that have these organs, "trichobacteria." There may be but one 
flagellum, situated at the pole {monotrichous) , or a number may be 
present (lophotrichous) . When they are situated at both poles the microbe 
is termed amphitrichous; when distributed over the whole body of the 
bacteria, peritrichous. The presence and the activity of flagella depend 
on many factors: on the condition of the medium, bacteria grown on 
liquid media being more active than those on solid; on temperature; 
on presence of air; on light; and on the age of the culture. They are 
easily broken off from the microbe, and care must be used in staining 
them. 

Involution Forms. — By involution form is meant the irregular 
appearance a microbe often assumes when its conditions of growth are 
unfavorable. Numerous bacteria melt together and become irregular 
chains, or they appear pear or club shaped. The protoplasm becomes 
retracted and irregular staining takes place. Sometimes forms with 
branching projections are discovered. These have often been described 
as involution forms, but are now more commonly regarded as normal, 
though unusual, structures. This applies to tubercle bacilli, diphtheria 
bacilli, and some others. This true branching (dichotomy) must not 
be confounded with false or pseudodichotomy due to mere apposition of 
separate organisms, as seen in various bacilli, streptococci, etc., and 
habitually in the cladothrices. 

Chemistry. — The bacterial cells are of variable composition, de- 
pending to a great extent upon the kind of nutrient matter, but all the 
principal chemical combinations of living matter are found among them. 
Water represents about 85 per cent . of their construction while the solids are 
made up of protein, from 10-14 per cent. (Nencki describes it as a mycopro- 
tein), fats about 1 per cent., traces of carbohydrates (of which cellulose is 
the most conspicuous because it is supposed to indicate the connection of 
bacteria with plants although it is not present in every kind of these 
microorganisms) and about 1 per cent of ash in which phosphates and chlo- 
rides of sodium, calcium and magnesium are the usual salts. The proteins 
are important because they represent the part from which the toxin is 
derived. Fats are important in certain groups only, the tubercle bacillus 
for example. Chlorophyl and bacteriopurpurin are in some way con- 
nected with bacterial pigments. Ferments are very important chemical 
agents and correspond in action to their analogues in animal tissue. 

BIOLOGY 

Bacteria may be divided into two great classes : those that live only 
on dead organic matter are termed saprophytes; those that develop in and 
at the expense of the living organism, parasites. These latter by their 
growth cause certain pathological conditions in the host, and are called 
pathogenic. By obligate saprophytes or parasites we mean those that 

17 



258 



A TEXT-BOOK OF PATHOLOGY 



can exist only under the conditions named ; by facultative saprophytes 
or parasites, those that can develop under either condition. 

Conditions of Growth. — Certain surrounding conditions are neces- 
sary to bacteria, and any marked change in them will inhibit the growth 
or totally destroy it. 

Mechanical Conditions. — A slight shaking of a liquid culture seems 
to help the development of bacteria, while a more violent and long- 
continued agitation destroys them. 

Physical Conditions. — Electrical currents destroy the growth, prob- 
ably by the action of certain products of the electrolysis and not by 
direct action. 

Light. — Diffused daylight inhibits the growth of bacteria: direct 
sunlight destroys them ; this is probably due to oxidation. While the 
arc light will have an inhibitory effect if applied to bacteria for a long time 
an d in high voltage, electric light has no practical disinfecting value. The 
z-ray behaves likewise, while radium rays have a higher value than 
either if applied at short range. 

Heat. — A certain temperature is necessary, the degree varying with 
the species of microbe. Most of the water bacteria and saprophytes 
grow between 0° and 30° C. (32° and 86° F.), the optimum being 15° to 
20° C. (59°-68° F.) (psychrophilic) . The pathogenic flourish between 
10° and 45° C. (50° and 113° F.), best at the body temperature, 37° C. 
(98.6° F.) (mesophilic) . There are some that develop well at 40° to 
70° C. (104°-158° F.) (thermophilic). Above these limits the members 
of the several groups are killed, and each bacterium has its own thermic 
death-point. That of most of the pathogenic varieties lies between 
50° and 60° C. (122° and 140° F.). Below the lower limit, down to the 
degree at which any multiplication will occur, the growth is inhibited 
only. Temperatures below zero destroy only the most feeble of para- 
sites. Very low temperatures ( — 250° C; — 418° F.) have been used 
without preventing the future development of the microbe. 

Spores are extremely resistant to higher temperatures. While 
no bacterium can live after exposure to 100° C. (212° F.), the spores of 
some of the earth microbes are killed only after exposure for an hour to 
steam heated to 115° C. (239° F.). 

Chemical Conditions. — The essential substances for the growth of 
bacteria are water, carbon, nitrogen and oxygen, and certain salts. 
For the carbon, they require already prepared carbon compounds, as the 
sugars, glucose, saccharose, lactose, etc., mannite, glycerin — in fact, 
most of such as are soluble in water. Most of the proteins and many ' 
simpler substances, even such as ammonium carbonate, furnish the 
nitrogen. Free oxygen is necessary for many microbes. Those for 
which this is absolutely required are termed "obligate aerobic." Facul- 
tative aerobes are those that grow best in the presence of oxygen, but 
may develop in its absence. Anaerobic microbes are those that grow 
best without atmospheric oxygen and are also obligate and facultative. 
They obtain it as they need it by reducing oxygen-containing materials 
in the culture-medium. It has been found possible to produce races 
which, although naturally obligate anaerobic, develop also in an atmos- 
phere of oxj^gen. 



BACTERIA. THEIR NATURE AND ACTION 



259 



FUNCTIONS AND PRODUCTS OF BACTERIA 

The study of the substances that result from the action of the life 
of bacteria and the changes that they produce in their various media 
of growth is really a branch of organic chemistry. The function of 
bacteria is essentially a destructive one. They split up the higher 
nitrogenous and non-nitrogenous compounds into simpler substances. 

The various substances that are found in cultures of bacterial 
growth comprise: (1) the components of the bacterial cell proper, as 
the proteins; (2) the secretions of the cell, as the ferments and toxins; 
and (3) substances that are the result of the action of microbes upon 
the medium of growth. The toxic substances in bacterial cultures may 
be classed as (a) intracellular and (b) extracellular, according as they 
are contained within the bacterial cell or are made from or excreted 
into the culture-medium. The extracellular substances may be purely 
products of bacterial secretion which have been separated from the 
cell, or they may be decomposition products derived from the culture- 
medium. 

The bacterial proteins may produce suppuration (pyogenic) or fever 
(pyrogenic) , or they may be the cause of an inflammatory process (phlogo- 
genic). These substances are comparatively resistant to heat and are 
thus sharply distinguished from the ferments and toxins. The best- 
known examples are mallein, derived from the bacillus of glanders, 
and tuberculin, from that of tuberculosis. These' are pyrogenic when 
injected into animals suffering respectively from glanders or tubercu- 
losis, but have no, or at least very slight, effect upon healthy subjects. 
Other proteins are shown to have similar effects on tuberculous animals, 
but not in the minimal doses which suffice when tuberculin is used. 

There are poisons however, whose relation seems to be very closely 
associated with the disease produced by the organism containing them, 
the so-called endotoxins; the most conspicuous bacterium having such 
a toxic moiety is the typhoid bacillus. They are characteristically 
bound closely to the bacterial cytoplasm and are only obtainable upon its 
death and disintegration, differing therefore from the preceding poisons 
in not representing the activity of the whole plasm, and from the toxins in 
not being excreted or metabolized in the surrounding medium. Thus 
cultures, freed of the bodies of the germs, will have no endotoxic value but 
if the bacterial mass be frozen and thawed or ground, these poisons are 
obtained. They do not call forth antitoxins, but, when freed, represent 
the division of the bacterium responsible for the appearance of specific 
precipitins, agglutinins and opsonins. They may be freed in old cultures 
by autolytic ferments and during infection by similar enzymes within the 
body. 

Vaughan and his associates claim that the protein of bacteria is 
divisible into a highly toxic non-specific portion, and a non-toxic fraction 
specific for each kind of organism. Upon this result and his further 
experimentation he has elaborated a theory of infection to be discussed 
later. The endotoxins are certainly closely bound with the bacterial 
proteins, but their exact seat is not known. 



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A TEXT-BOOK OF PATHOLOGY 



The second group of products includes the ferments and possibly 
the toxins. 

Ferments. — A ferment is a complex body about which we know 
but little except the effects that it produces. By its presence, and 
probably without entering into intimate chemical combination, it pos- 
sesses the power of breaking up more highly organized nitrogenous and 
non-nitrogenous compounds into simple and more diffusible molecules. 
They are termed enzymes or unformed ferments in contradistinc- 
tion to the bacteria themselves, which are called formed or living fer- 
ments. That the action of ferments is not due directly to the microbe 
is shown by the facts that bactericidal substances, such as phenol (5 per 
cent.), chloroform, ether, etc., have no effect on- them, and that cultures 
freed from bacteria by filtration still possess fermentative power. The 
action of ferments is termed fermentation, but this term is more especially 
limited to the effect of certain ferments upon non-nitrogenous compounds, 
particularly the carbohydrates. The result of fermentation upon nitro- 
genous material is called putrefaction., which generally occurs with, 
though often without, the formation of odorous gases and other sub- 
stances. The intracellular origin of certain ferments has been demon- 
strated by their experimental separation from the bacteria when placed 
under high pressures. The resulting bacteria-free liquid possesses the 
same fermenting qualities as the culture itself. 

The ferments, like toxins, are of unknown composition, are highly 
destructible by chemical agents and heat, cause effects out of all pro- 
portion to their bulk or amount, and are frequently mechanically pre- 
cipitated with various indifferent bodies. When injected into animals 
both are capable of exciting the formation of antibodies (anti-ferments 
and antitoxins). 

Bacteria, as animal cells, have autolytic ferments. In this self-solu- 
tion certain substances are freed that may be of importance in immunity 
reactions — endotoxins and aggressins. The exact relation of bacterial 
digestion products, whether autolytic or by the agency of - blood-serum 
or tissue fluids, is not exactly known. The demonstrable enzymes of 
bacteria have little to do with the specific infection caused by the growth 
aside from the softening of exudates and the like. This example 
is given to show also that one of the most important enzymes of bacteria is 
proteolytic in action. 

The principal bacterial ferments are: 

Proteolytic Ferments. — These transform albumins into more soluble- 
and diffusible substances. One form very often met with is that which 
liquefies gelatin. This acts in an alkaline medium, and is, therefore, 
akin to the animal ferment trypsin. This liquefaction of the gelatin 
affords a means of distinguishing many species of microbes. 

Diastatic Ferments. — These transform the starches into sugars, 
and are found in many bacterial cultures, as of Bacterium mallei, B. 
pneumoniae, etc. 

Inverting Ferments. — These change the non-fermentiscible sugars 
into those that undergo direct fermentation. Such ferments are found, 
for instance, in cultures of Spirillum choleras, and S. metschnikovii. 



BACTERIA, THEIR NATURE AND ACTION 



261 



Coagulating Ferment. — One of the means of differentiation of bacteria 
is the coagulation of milk used as a culture-medium for the bacteria 
under observation. This coagulation is due not to acidity produced 
in the medium, but to the action of a ferment. 

Some varieties of microbes produce a ferment that has the power 
of dissolving this coagulum when formed (casease); and still others 
produce both ferments — the coagulating and the dissolving. 

Hydrolytic ferments are exemplified by such as break up urea 
into ammonium carbonate and hippuric acid into glycocol and benzoic 
acid. 

Fat-splitting ferments split the fats into glycerin and the fatty acids. 

Oxidizing and nitrifying ferments are other less important forms. 

Effects of Ferments. — The single or combined action of these 
various ferments causes certain special kinds of fermentation distin- 
guished by the principal substance produced. Alcoholic, lactic acid, 
and butyric acid fermentation of the sugars, acetic acid fermentation of 
alcohol (Bacillus acidi lactici, B. butyricus, B. acidi butyrici, etc.) ; cellu- 
lose fermentation with the production of carbonic acid gas and ammonia; 
nitrification, in which oxidation of ammonium leads to production of 
nitrates (Winogradsky's nitrosomonas) , and secondarily conversion of 
nitrates into nitrites (nitrobacter) ; mucoid fermentation of glucose and 
invert-sugar are examples. 

Toxins. — The pathogenic bacteria produce certain toxic substances 
that are akin in action to the poisonous venom of certain serpents and 
other animals, and to certain poisonous principles of plants, as abrin 
and ricin, and are almost certainly of protein nature. These are of in- 
definitely determined character, and act deleteriously upon the host 
only after the lapse of a certain time — a period of incubation. They 
are considered the specific toxins of the several bacteria. According to 
some, these give all the reactions of albumin, and have been termed 
toxalbumins (Briegar). It is probable, however, that the toxalbumin 
is but an impure form of the true toxin, a combination of it and various 
substances derived from the medium of growth. Most recent investiga- 
tors look upon the toxin as akin to the ferments. Roux and Yersin, in 
their monograph on the diphtheria bacillus, held this view and more 
recent investigators support the theory. The analogous pathological 
action of the toxins and ferments, their common origin, their destruc- 
tion (oxidation) in the presence of light, their precipitation by alcohol, 
their precipitation from solutions by colloid bodies, their long and im- 
perfect dialysis, all point to this. High temperatures affect both similarly, 
both being destroyed at from 60° to 100° C. (140°-212° F.) Chemical 
substances that have no effect (chloroform, ether, etc.) on the ferments 
are without action upon the toxins; and, vice versa, those that destroy 
the ferments (formaldehyd) are also injurious to toxins. They are, 
curiously enough, digested by proteolytic ferments. Both may be 
swallowed with impunity, although they are pathogenic when injected 
subcutaneously or intraperitoneally. When the microbe is grown 
in some inorganic medium or in a non-albuminous one (as Uschinky's 
solution), the toxic principle obtained corresponds in its chemical reac- 



262 



A TEXT-BOOK OF PATHOLOGY 



tions to a ferment. Most important is the fact that extremely minute 
doses are effective. Ferments act without regard to the mass em- 
ployed, and it would seem that toxins act in almost imponderable 
amounts. It has been estimated that Mooo g m - of tetanus toxin will 
kill a horse weighing 600 kg. — six hundred million times its weight; and 
that Mooo m g- of tuberculin causes a reaction in a diseased man weigh- 
ing 60 kg.- — sixty trillion times its weight. Finally, both act only after 
a definite period of incubation. 

Considerable light has been thrown upon the nature of toxins by 
the investigations of Ehrlich and others who have followed him. 
These investigations have been mainly concerned with the be- 
havior of the toxin toward the antitoxin bodies. Ehrlich has found 
that the serum contains at least three distinct substances: the toxin 
proper, toxoid, and toxon. The toxin is the active poisonous element; 
but, aside from its toxic property, it has a distinct combining ability, 
so that it enters into combination with antitoxin. A given serum, how- 
ever, will combine with a greater quantity of antitoxin than the toxic 
power of the serum would indicate. In other words, there are other 
combining bodies which have no toxic power, or less toxicity than the 
toxin. A serum as it grows older loses in toxic power without losing in 
combining power. This is due to the conversion of toxin into toxoid. 
The toxon has, similarly, the combining power for antitoxin, but is 
slightly toxic, being capable, in the case of diphtheritic serum, for ex- 
ample, of producing the postdiphtheritic paralyses. It is, however, not 
a derivative of the toxin, but results from a direct action of the bac- 
terium, and is produced simultaneously with the toxin. The dissocia- 
tion of combinirjg power and toxic power is explained upon the assump- 
tion that each molecule of toxin contains a group of atoms specially 
adapted for combining with vulnerable cells or with antitoxin and a 
toxic group. To the former the name haptophore group and to the 
latter the term toxophore group has been given. The probable nature 
of these will be referred to in the discussion of Ehrlich's theory of 
immunity. 

Fate of Toxins. — It is certain that there exist in various cells of the 
animal organism certain oxidizing ferments by which the toxin is de- 
stroyed. Not all of the toxin is thus oxidized. A part is eliminated 
unchanged through the kidneys in the urine and to some extent through 
the liver in the biliary secretion. Besides these there is still another 
method of defence of the organism against the action of toxin — the 
antitoxin (q. v.). 

Products in Culture-medium. — The third group of poisons found 
in bacterial cultures are the products of decomposition of the culture- 
medium under the influence of the bacterial growth. This is the class of 
poisons called ptomains, protein degradation bodies, with their nitrogen 
in the amino form. They act as a direct posion and require no specific 
incubation period. They differ from toxins in the fact that their elab- 
oration is more closely dependent on the character of the medium than is 
that of the former. The toxin of tetanus or diphtheria may be produced 
in various, even in non-albuminous, media, but the elaboration of certain 



BACTERIA, THEIR NATURE AND ACTION 



263 



ptomains and other decomposition products is more narrowly restricted 
to growth of certain organisms in appropriate media. The substances 
produced by bacteria from the culture-media and tissues are varied and 
numerous. Besides those produced by the various fermentative processes 
there are: the products of digestion of albumin, albumoses, peptone, etc.; 
the ptomains; nitrogenous substances, as leucin and tyrosin, methyl-, di- 
methyl-, ethyl-propylamins ; organic fatty acids, formic, acetic, propionic, 
butyric, margaric, lactic, etc.; certain aromatic compounds, as indol, 
phenol, kresol, skatol, mercaptan, hydrochinon, etc.; and finally, hydro- 
gen, carbonic dioxid, hydrogen sulphid, ammonium, water, etc. All 
of these are more or less toxic and may contribute to the unfavorable 
action of bacteria, but are not the specific toxic agents that occasion the 
characteristic pathological effects of the various micro-organisms. 

Chromogenesis. — -Many bacteria form colors which give to the 
culture a characteristic appearance. The production of the pigment 
depends to some extent upon the constitution of the medium, and it is 
possible to produce cultures and even races of pigment-forming bacteria 
by the use of appropriate media. It has no importance in the patholog- 
ical relations of the organisms. 

Photogenesis. — -The phenomenon of phosphorescence observed 
in decaying fish is due to the action of bacteria. This production of 
light is observed in many of the cholera group of vibriones. 



THE LOCAL EFFECTS OF BACTERIA 

These may be either (a) mechanical or (&) histological, the mechanical 
effects being least in importance, (a) Sometimes masses of micro- 
organisms more or less completely occlude small blood-vessels and 
occasion, secondary changes in the tissues in this mechanical way. In 
other cases the obstruction is incomplete, but occasions thrombosis in 
the blood-vessels and areas of necrosis in the region thus deprived of 
blood; hemorrhagic extravasations are not uncommon in such cases, (b) 
The histological changes occasioned by bacteria are proliferative and 
destructive, among the latter being various degenerations and necroses. 
The proliferative changes may be non-specific or specific — that is, there 
may be simply proliferation such as occurs from any irritation, or there 
may be special forms of proliferation more or less characteristic of the 
individual micro-organism in extent, distribution, and nature. This is 
seen in the peculiar lesions of tuberculosis, glanders, rhinoscleroma, etc. 
The cellular degenerations and necroses occur coincidentally or subsequent 
to the proliferative changes. On the contrary, in many cases the first 
effects of bacterial invasion seem to be degeneration or necrosis of the 
tissues immediately around the organisms. It would seem from late 
observations that the exact reaction following the primary settlingjof an 
infecting microbe depends upon whether it is able by toxin formation, to 
destroy normal oxidative processes, in which case necrosis is apt to occur, 
or to act primarily with positive chemotactic power in which case local 
suppuration usually appears. There is a rough parallelism [between 



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virulence and primary necrotizing power whereas the early appearance of 
leucocytes on the field is a token of more resistance on the part of the 
host. In either case the final reaction is like that described under 
inflammation, the exact kind depending upon pathogenicity, virulence 
and resistance (see below). 

EFFECT OF TOXIC PRODUCTS OF BACTERIA 

This section of the subject is devoted to a consideration of the 
modus operandi of the foregoing bacterial products upon the body. 
The general principles apply to protozoan and metazoan parasites, but 
we deal here chiefly with bacteria. The action of all the animal parasites 
is not understood, and comment upon them will be reserved for the 
appropriate chapter. 

Infection is the successful invasion of the tissues by bacteria and the 
evidences of their presence. Infestation is the term applied to the 
presence and action of animal parasites within the body. It is not our 
intention to go deeply into the subject of the origin of infection at this 
point, a brief review of it being given in a later chapter, nor to discuss 
hygienic principles, which should be sought in works upon that topic. It 
is well however, to call attention to the objects and routes by Which the 
causative agents of infection reach the interior of the body for everything 
we touch or swallow, indeed the air we breath when in association with 
human beings or lower animals, contains bacteria or viruses of some sort. 
This ubiquity enables them to be present almost constantly on the skin 
and mucous surfaces, so that it is not wonderful to learn that even 
pathogenic germs may be constantly in a position to penetrate our pri- 
mary defenses when the chance permits. They are held in abeyance or 
destroyed by the skin and mucous membranes. Should a lowering of 
these defenses or a great increase in the invasive powers of the bacteria 
occur, infection follows. The character of the infection depends somewhat 
upon the portal of entry or so-called infection atrium. Typhoid bacilli 
will not produce typhoid fever if rubbed upon the skin, but may if 
swallowed. Pus cocci may cause furunculosis if rubbed upon the skin, 
but will not if swallowed. 

All openings to the body present possible infection-atria, and pre-exist- 
ing disease of any part lowers the resisting powers of that part in par- 
ticular and possibly of other parts. Injury or circulatory deficiency to a 
part renders it less resistant to local infections, while such factors as 
overwork, exposure, malnutrition, intemperance of any sort, may have a 
similar effect for the body as a whole. (See also mixed infection.) The 
most important infection-atria are the respiratory and alimentary tracts. 
Bacteria are inhaled or swallowed and lodge upon the mucous membranes. 
As has been said, these membranes are part of the primary defenses, but 
it has been shown that bacteria may pass them without leaving a trace. The 
secretions of the body, saliva, gastric and intestinal juices, bile, have a 
mildly restraining influence upon bacteria within them, but any mechanical 
disturbance of outflow, or congestion seems to decrease this. The in- 
vaders are met then by the resistance of the lymphatic system in which 



BACTERIA, THEIR NATURE AND ACTION 



265 



they are carried through the lymph-channels, or by the antibacterial 
power of the blood. The leucocytes are very important in meeting and 
devouring invaders, but this very process sometimes spreads infection, 
for the phagocyte may transport the microbe and itself go to pieces in 
transit, leaving the infective agent free to work at a place far from its 
portal of entry. The lymph glands are very valuable niters taking care 
of much detritus and perhaps many living bacteria; they are probably 
responsible for the practical sterility of the tissues generally. 

Pathogenicity is the power of the germ to produce disease. This 
does not always run parallel with virulence, as will be seen in the sub- 
acute infections. The power of the germs to resist the bodily defenses 
and, by their extra- or intracellular poisons, to produce a pathological 
effect, is their virulence. Ehrlich explains virulence by the statement 
that a bacterium is virulent to the extent that it has haptophorous or 
binding receptors to bind and sidetrack the defensive receptors of the 
body tissues. (See pp. 275, 276, and Immunity.) 

An attractive theory has been suggested by Bail to explain the 
unusual virulence of micro-organisms under certain circumstances. 
It was found by Koch that intraperitoneal inoculation with fresh cul- 
tures of tubercle bacilli causes a rapid destruction of tuberculous ani- 
mals. Bail found that if tubercle bacilli and sterilized tuberculous 
exudate were injected into healthy animals, sudden death resulted. 
Neither the sterile exudate nor the tubercle bacilli alone had such an 
effect. He, therefore, assumed that something in the exudate increases 
the virulence of the micro-organisms and gave the name "aggressin" to 
the hypothetic substance. The exudate found in the peritoneal cavity in 
these cases was found to consist solely of lymphocytes, and Bail suggests 
that the aggressin acts by paralyzing the polymorphonuclear leukocytes 
and thus prevents phagocytosis. The lymphocytic character of tuber- 
culous exudates is explained by the presence of the aggressin in the tuber- 
culous animal or man, and the consequent prevention of migration of 
polymorphonuclear leukocytes. Similar phenomena have been found 
in cases of other micro-organisms. Anti-aggressins have been produced 
by repeated inoculation of animals with exudates containing the 
aggressins. 

Some bacteria or their toxins have a predilection for certain tissues, as 
for example, tetanotoxin for the nervous system. This and other, 
phases of virulence will be considered -under Immunity. 

The probability of a successful infection varies directly with the 
number of organisms introduced, the virulence of the invaders, and 
with the resistance offered by the individual. 

Intoxication and Infection. — In one class of diseases the in- 
fecting microbe remains localized at the point of inoculation, and is 
never or only exceptionally found in the fluids of the body, the general 
symptoms of the disease being due to absorption of the toxic products. 
In such cases the general symptoms of the disease are true intoxica- 
tions. In other cases the microbe is found circulating in the blood 
throughout the body and finds lodgment in most of the organs. These 
are called infections in the strict sense. Tetanus is the type of the 



266 



A TEXT-BOOK OF PATHOLOGY 



first class; anthrax, of the second. There is, however, no distinct line 
to be drawn, for the symptoms of all infections are doubtless due to 
toxins or other toxic products, whether produced locally at the point of 
implantation of the organism or throughout the body when it is dissem- 
inated. The distinction between intoxication and infection depends 
upon the method of toxin production. 

The intoxications form a small class, of which diphtheria, tetanus, 
and botulism are the only practically important members. These 
diseases are due to extracellular poisons, commonly called toxins, 
which are made from the medium upon which the bacteria are living. 
For example, diphtheria bacilli growing on the pharynx pervert the 
normal bodily protoplasm to a toxic form. The toxin is negatively, or 
at least anti-chemotactic (see Inflammation), and thus prevents the 
phagocytic action of the leukocytes, while most other bacterial products 
and the bacterial proteins are positively chemotactic. 

The second class, the infections, is much larger. While it is possi- 
ble that a modicum of extracellular poison is formed by microbes 
causing infection, it is certain that by far the greater amount is not 
available until the bacterial body is digested and the protoplasm liberated 
(endotoxin). The lysis of the germs may be focal or in the 
circulation, in either case due to the bacteriolytic power of the blood 
or to phagocytosis. Under Immunity and Allergie theories of the 
pathological action of these toxins will be discussed. 

A virulent microbe is one that invades the animal body and there 
produces its more or less powerful toxin; an avirulent one produces but 
little, if any, toxin, and is destroyed by bacteriolytic substances and by 
phagocytosis, either with or without suppuration. The number of or- 
ganisms, as well as the virulence, is important in determining the char- 
acter of the effects. 

Sapremia, Septicemia, and Pyemia. — Absorption of the products 
of protein autolysis or bacterial destruction of body tissues gives rise to a 
sort of poisoning known as sapremia that does not follow the usual course 
of specific infections. It arises especially when a necrotic area of large 
size lies near a good blood supply that can absorb the disintegration 
products and is seen with retained secundines after parturition or in 
cases of gangrene. 

We have seen that infection may result in the spread of bacteria 
via the circulation; when this is combined with deleterious effects at 
various points it is termed septicemia, well exemplified in typhoid 
fever. When, however, the microbe is carried to various parts of the 
body and there gives rise to secondary suppuration, the condition 
is called pyemia. Bacteremia is a term that may be used to indicate 
merely the circulation of bacteria in the blood without implying any 
clinical condition. 

Infections may also be divided into fulminating, acute, chronic, and 
Adami's subinfection. 

Fulminating infections are sudden overwhelming attacks by bacteria, 
in which all bodily defenses are destroyed and death results before new 
defenses can be raised. 



BACTERIA, THEIR NATURE AND ACTION 



267 



Acute infections are those manifested by a short clinical course of 
more or less definite type and are the evidences of a brief depression of 
bodily defenses. They tend to be self -limited. 

Chronic infection is the expression of struggle between the disease 
agent and bodily defenses over a long period and without definite stages. 
Tuberculosis is typical of such a disease. 

Between this and the second form there is another, called variously 
subacute and chronic remittent. This may be a continuation of an acute 
condition or arise insidiously and cryptogenetically. The cases have 
constantly some evidences of infection, but are subject to remissions, 
acute in form, followed by disappearance of the more evident signs of 
infection when the exacerbation has passed. In cases studied by us 
there is persistent bacteremia. The cause seems to lie in a condition 
of balance between the bodily defenses and the bacterial offenses. 
Sometimes we have found that the failure of defense is on the part of the 
leukocyte; at others, on the part of the serum. The bacteria in these 
cases are in a condition known as "fast" or "fixed," a state in which 
they seem to have immunized themselves in some way against the bodily 
defenses, and in so doing do not give rise to new defenses or antibodies. 
The bacteria may be considered as possessing a fairly well-marked path- 
ogenicity, but a low virulence. 

Subinfection, according to Adami, is a condition of repeated infec- 
tion from the bowel or respiratory tract due to congestion or mild 
inflammation. These changes enable bacteria or their products to 
pass to the lymph or parenchymatous organs, where they are de- 
stroyed, their remains being found as amorphous granules resembling, 
but distinguishable from, pigment. The effect is that of continued or 
repeated irritation, and Adami believes they are factors in the production 
of cirrhosis and anemias. 

The term focal infection has become fairly well fixed in medical par- 
lance, whether or not in complete justice remains to be seen. It implies a 
condition similar to the foregoing but including the existence of an area of 
weakly active inflammation, perhaps causing few symptoms or signs, 
from which bacteria or their products now and then sneak into the blood 
stream to be deposited in some place, there to excite a similar moderately 
active disease. It is best exemplified by disseminated arthritis originat- 
ing in pyorrheal pockets, and commonly due to streptococci. 

Mixed Infections. — This is a state in which the effect of one agent is 
superimposed upon another, with usually an intensification of the symp- 
toms or a rendering of them slightly atypical. In general the existence 
of one well established bacterial disease reduces the resistance of the host 
to others, either by creating new atria or by so perverting the physiology 
of the usual ones so that their defense is removed. As a matter of fact in 
chronic diseases, death is perhaps nearly always due to some secondary 
invader, such as the streptococci in pulmonary tuberculosis. In 
disorders of non-bacterial nature, cardiac and renal disease for example, 
there is a reduction of resistance, and toward the end terminal infection 
supervenes; this usually takes the form of pneumonia, erysipelas or 
enteritis. 



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A TEXT-BOOK OF PATHOLOGY 



IMMUNITY 1 

Definition. — In the present state of our knowledge of the condi- 
tion of immunity it is most difficult to give a precise definition of this 
term. It denotes that condition of an organism which enables it to 
resist the attacks of bacteria and their toxic products. In one sense 
it is the reverse of susceptibility. An animal that is not susceptible to 
an infection is said to be immune, and the term "immunization' is ap- 
plied to the process by which an animal becomes thus refractory. 

Varieties. — Two principal forms of immunity, with a number 
of subdivisions, are recognized: (a) Natural immunity; {b) Acquired 
immunity. 

(a) Natural immunity is the power of resistance to bacteria and 
toxins manifested by races or classes of men and animals, or even by 
certain individuals. It is always or nearly always an inheritance from 
immune ancestors, and can readily be accounted for on the principles 
of heredity. We may distinguish: 

1. Natural Bacterial Immunity.- — In this case the resistance is offered 
to some specific bacterium. Thus, none of the lower animals is suscepti- 
ble to naturally acquired syphilis, measles, or leprosy; man is insus- 
ceptible to rinderpest; dogs and Algerian sheep, to anthrax; chickens, 
to tetanus; and in epidemics of various kinds some individuals regularly 
escape. This bacterial immunity 2 is only exceptional^ absolute; usually 
it is merely relative, the susceptibility or insusceptibility varying with 
the environment or individual conditions. 

2. Natural Toxin Immunity. — Just as the hog is naturally resistant 
to snake-venom, so certain animals are immune to certain bacterial 
toxins. Rats are resistant to diphtheria toxin; chickens, to tetanus 
toxin, etc. 

(b) Acquired Immunity. — This may be naturally acquired, as when an 
animal has passed through an infectious disease; or artificially acquired, 
when an animal or man has been inoculated with bacteria or bacterial 
products. We may again distinguish two subvarieties, as in the case 
of natural immunity: 

1. Acquired Bacterial Immunity. — In this form the animal or man 
has been rendered immune by previous naturally acquired disease, or 

1 Certain definitions and synonyms must be understood to read properly this and 
other articles on immunity : 

Antigen, or exciting substance, is the bacterium, cell, or substance used for immu- 
nizing to produce antibodies; these, then, are substances formed against antigens. 
Toxin, ferments are the soluble products of disease agents. 
Toxophore, the poisonous or intoxicating fraction of an antigen. 
Haptophore, the binding fraction of antibody or antigen. 

Complement, cytase, alexin, the normal thermolabile antisubstance in blood-serum. 

Zymophore, the toxic radical in agglutinins and precipitins. 

Cytophile fraction of antibody combines with cells. 

Complementophile fraction of antibody combines with complement. 

Immune body, amboceptor, intermediate body, fixateur, substance sensibilisatrice, 
preparateur, copula, and desmon are synonyms for the thermostabile body raised 
against antigens. 

2 The various immunities of animals are not always absolute under experimental 
conditions. It is possible to give monkeys and, probably, rabbits syphilis, but they do 
not have syphilis as an endemic among them; it is not natural to lower animals. 



BACTERIA, THEIR NATURE AND ACTION ' 269 

by inoculation with the specific organisms that have been first reduced 
in virulence or killed by heating and other means. Acquired bacterial 
immunity does not follow all infections. In the case of gonorrhea, 
for example, it is wanting; and in erysipelas there seems to be increased 
susceptibility; but in most of the infections immunity is produced. 
It is of variable duration, sometimes lasting throughout life, some- 
times only brief periods of time. 

2. Acquired Toxin Immunity. — In this form the immunity is pro- 
duced by the injection into animals of the toxins from bacterial cultures, 
or by injection in men or animals of serum of animals that have been 
rendered naturally or artificially immune. 

The terms "active" and "passive" are used in connection with types 
of immunity to designate the active or passive part taken by animals 
or men in the acquisition of the immunity. 

Active Acquired Immunity. — This term is applied when artificial 
bacterial immunity or toxin immunity has been produced by inocula- 
tion with living or dead bacteria or by injection of filtrates of cultures, 
because in these cases there is active production of the immunizing sub- 
stances in the body of the experimental animal. 

Passive Acquired Immunity. — This term is applied to the protec- 
tion afforded by injections of serum of immune animals, because in 
this case the process is passive as far as the recipient of the antitoxic 
injection is concerned. Active immunity is relatively much more last- 
ing than passive. 

In many cases immunity asserts itself against both the infecting 
microbe and its specific toxin, as in the rat with regard to the diphtheria 
bacillus and its toxin; but more often an animal is resistant to the 
infection, though susceptible to the toxin. An example of this is the 
action of the guinea-pig toward tetanus (Vaillard). The reverse may 
be true, and we see an injection of tuberculin without effect upon a 
healthy animal that is very susceptible to tuberculous infection. Most 
commonly natural immunity exists toward the infecting microbe and 
not its toxin. 

Theories of Immunity. — All the phenomena of immunity have not 
been satisfactorily explained, but the subject is at least much clearer 
than formerly. 

Bacterial Immunity. — Alexin Theory. — The blood-plasma and fluids 
of a naturally immune animal are capable of destroying the bacteria 
toward which the animal is immune. That the destructive agent is 
contained in the blood itself is shown by the fact that the defibrinated 
blood and pericardial effusions of dogs and rabbits destroy anthrax 
bacilli outside the body. This bactericidal action is not, however, 
specific nor confined to serum from animals naturally immune to certain 
infections. On the contrary, the destructive action is manifested 
toward all micro-organisms in varying degrees, and the serum of man or 
animals always manifests bactericidal power, though not always de- 
cidedly. This bactericidal action was attributed by Buchner to certain 
albuminous bodies which he termed "alexins." These are unstable 
substances resembling ferments in action and easily destroyed by heating 
the serum to from 55° to 60° C. (131°-140° F.). It has been shown that 



270 



A TEXT-BOOK OF PATHOLOGY 



the protection in bacterial immunity is not afforded by a single body or 
alexin, but by two distinct substances, each of which is necessary. 
(See Ehrlich' s Side-chain Theory.) 

Phagocytosis. — Metschnikoff proposed the very attractive theory 
of phagocytosis. He has, however, modified his older views because of 
new experimental work along the lines laid down by Ehrlich. He now 
maintains that phagocytosis is the principal factor in immunity and that 
soluble immune bodies in the plasma are derived from leukocytes. Even 
extracellular digestion of bacteria is due to substances from leuko- 
cytes. The infecting microbes are taken up by certain cells of the 
organism and are destroyed by intracellar digestion, or are dissolved by 
ferment-like bodies derived from phagocytes when they break (phago- 
lysis). These cells — phagocytes — are of two kinds: the microphages, 
including the polymorphonuclear leukocytes; and the macrophages, in- 
cluding mononuclear leukocytes, the vascular endothelial cells, cells of 
the bone-marrow and spleen, certain connective-tissue cells and Kup- 
fer's cells, and even those of the nerve and muscle tissue. The micro- 
phages are mainly concerned in the absorption and destruction of 
bacteria; the macrophages, in the destruction of cells, portions of dead 
tissues, and the like. After injection of a culture into the subcutaneous 
tissue of an animal naturally or artificially immune, he noticed that 
the bacteria were all taken up by the leukocytes. That these microbes 
were still living and virulent, and were not taken up as mere dead matter, 
Metschnikoff regards as fully established. One proof he cites is the 
fact that an exudate containing no free bacteria, but all intracellular, 
is capable of producing cultures on artificial media and causing infection 
in susceptible animals. The ferment freed by disintegration, of phago- 
cytes Metschnikoff called "cytase." 

Certain important features of MetschnikofFs theory and results must 
be emphasized. Increase of resistance to bacteria is usually associated 
with an increased phagocytic power, but not always, and occasionally 
an infection, during which the blood and leukocytes possess high pha- 
gocytic power, results fatally. In some infections an immunity results, 
although we cannot perceive any change in the leukocytes. It has not 
been proved that antibodies arise from phagocytes. The cellular theory 
of Metschnikoff is not incompatible with the humoral or side-chain 
theory of Ehrlich, but merely explains certain phases of immunity 
reactions. The phagocytes are, undoubtedly, very important bodily 
defenses. One or the most difficult 'phases to explain in terms of this 
theory is the mechanism of the ill-understood increase in virulence. 
Organisms are resistant to phagocytosis directly as virulence changes, 
yet it is possible to get an immunity to a virulent organism without 
phagocytic action. 

Bacteriolytic Theory. — Pfeiffer opposed to Metschnikoff' s theory 
the experiment of injecting cholera vibriones into the peritoneum of 
artificially immunized guinea-pigs. He observed a complete destruc- 
tion of the microbe by the peritoneal fluid — an agglutination into 
masses and a gradual degeneration. There were few, if any, leukocytes 
present, and he, therefore, claimed that such destruction was entirely ex- 
tracellular and humoral in character. This property of destroying or 



BACTERIA, THEIR NATURE AND ACTION 



271 



dissolving bacteria has been termed the "lytic" action of serum. How- 
ever, if a prehminary injection of some substance that determines a local 
leukocytosis is made, there may occur, instead of the reaction of Pfeiffer, 
a true phagocytosis. Metschnikoff interprets Pfeiffer' s phenomenon 
as the result of a dissolution of the leukocytes by bacterial action, and 
solution in the peritoneal fluid of the bacteriolytic substances. 

While an important part must be admitted to phagocytes in the 
ultimate destruction of bacteria, bacteriolysis may occur independently 
of phagocytes. 

The bacteriolytic substance has been found to operate outside of 
the body, though not so actively as in the peritoneal cavity. When 
it has been partly destroyed by long standing or heat, the addition 
of a small quantity of normal serum from the same animal species restores 
the bacteriolytic power. (These phenomena will be again referred 
to in the discussion of Ehrlich's Theory.) The sources of the bacterioly- 
tic substances are the spleen, bone-marrow, lymphatic glands, thymus 
gland, and doubtless other organs as well. It is probable that the source 
differs in different infections. 

Bacteriolysins differ from Buchner's alexin in being specific in action, 
and, therefore, operative only in the case of bacteria to which the 
animal has been immunized. The bacteriolysins are closely related to, 
if not identical with, hemolysins, substances occurring in the plasma 
under certain conditions and capable of destroying red blood-corpuscles. 
(See Ehrlich's Theory.) 

Opsonins.- — Wright and others have demonstrated in the serum 
of animals certain thermolabile bodies which, acting upon bacteria, 
sensitize them for phagocytosis. These substances, which have been 
termed opsonins, are analogous in constitution to toxins in having a 
haptophore group by which they attach themselves to the bacteria, and 
an opsoniferous group, which resembles the complements, and, acting 
like a ferment, completes the sensitization of the bacterium. 

The natural serum opsonin is thermolabile, but that arising in im- 
mune animals is decidedly more resistant to heat. It is believed by 
many that native opsonin is akin to complement or alexin, while that 
appearing after active immunization is in the nature of a specific anti- 
body and, therefore, a new development. Such antibodies are certainly 
specific for the type of organism, if not individually specific. There has 
been a tendency to minimize the effect of the leukocytes by those 
engaged in opsonin work. The phagocytes are not inactive or neutral, 
leaving all the work to the serum opsonin. Whether or not we accept 
the theory that all such free serum bodies come from the leukocytes, 
these cells are undoubtedly responsible for certain increase or decrease 
of phagocytic power, as we have found in certain subacute infections 
(see p. 267). Leukocytes and their extracts have, a slight bactericidal 
effect in vitro, as shown by Petterson. This may have some effect in vivo, 
but such an action is not considerable. The substances extracted from 
leukocytes are called "endolysins" by Petterson. 

The knowledge of opsonins and phagocytosis has led to the modern 
uses of dead bacteria or their products for increasing immunity. This 
process has been called vaccination because of its similarity in principle 



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A TEXT-BOOK OF PATHOLOGY 



to the antismall-pox vaccine. In typhoid vaccination there may be no 
high tide of opsonin or other antibody value maintained for a great 
length of time, but after exposure to typhoid there seems to be a prompter 
and greater response in the vaccinated than in the unvaccinated person. 

Bacterial Agglutination. — Investigations by Gruber, Durham, Widal, 
and others have shown that the serum of animals or men rendered 
immune (naturally or experimentally) to infection with the bacilli 
of typhoid fever, cholera, the bacillus coli, etc., causes agglutination 
and flocculent precipitation of the respective bacteria from their 
bouillon cultures. Such reactions may be obtained with dead bacilli 
under certain conditions and even with inert matters held in suspension. 
(For further details see Typhoid Fever.) This phenomenon {reaction 
of Gruber-Widal) has been interpreted as representing the mode of de- 
fence of the body against infection, and the reaction has, therefore, been 
considered as one of immunity. The reaction, however, bears no rela- 
tion to the severity of the infection or the degree of immunity. The 
serum may be highly agglutinative and yet have no immune properties. 
Some observers would have us believe that a close relation exists 
between agglutination, phagocytosis and infections. Intravital aggluti- 
nation will occur if agglutinating serum be injected into an already 
infected animal and it has been shown that phagocytes will devour the 
clumped organisms better than free ones. With this in mind it has been 
thought that infection and bacteremia will result if no agglutinim is 
present to pave the way for phagocytosis. There may be this coopera- 
tion in certain cases but the two processes are due to two different com- 
ponents of the serum. 

Experimentation seems to show that two substances are concerned 
in agglutination — an agglutinable and an agglutinating body. The 
latter appears to be albuminous or related to serum-globulin, as it is 
precipitated with the latter by magnesium sulphate. It is much more 
resistant to heat than alexin, being destroyed at 70° C, 158° F. 

Ferment Theory. — A ferment theory has been offered in explanation 
of some of the phenomena of immunity, but it is of only restricted inter- 
est or importance. Certain bacteria, like pyocyaneus, typhoid, and 
cholera bacilli, are capable of elaborating ferment-like bodies that have 
been designated pyocyanase, typhase, and cholerase. These have some 
bacteriolytic power, and natural immunity has been explained by 
assuming the presence in the plasma of such ferments. The action of 
these ferments is not, however, specific, and their relations to other 
bacteriolytic bodies is still obscure. 

Toxin Immunity. — The probable nature of toxins has been dis- 
cussed on page 261. It is found in some cases that an animal is suscep- 
tible to the action of the toxin of a certain bacterium, though refractory 
to the bacterium itself, and the reverse may also occur. It is clear, there- 
fore, that the resistance to bacteria and to toxins are distinct processes, 
though the two are in most cases associated in the same animal. 

Natural Toxin Immunity. — ■ Certain classes of animals exhibit natu- 
ral toxin immunity just as we have seen natural bacterial immunity 
existing in certain animals. The immunity of the hog to snake 
venom, of the chicken to tetanus toxin, of the rat to diphtheria 



BACTERIA, THEIR NATURE AND ACTION 



273 



toxin, and other examples might be cited. The explanation of this 
natural immunity is still uncertain. It is supposed that the immunity, 
which is an hereditary one, originally occurred in the ancestors as a 
result of the infection or intoxication in question. They then trans- 
mitted the immunity to their descendants. With the discovery of 
antitoxin (to be described below) it seemed likely that an explanation 
of natural toxin immunity has been discovered, but it was found that, 
in the case of the chicken and rat, not a trace of antitoxin is present 
in the blood, though these animals are highly immune to the toxins 
of tetanus and diphtheria respectively. It was also found that in these 
animals the introduction of the toxins, while producing no symptoms, 
rendered the serum highly toxic, and that, transferred to other animals, 
this serum produced the symptoms of the disease named. The toxin 
evidently circulates in an unaltered state at least for some time, and the 
immunity is not due either to destruction of the toxin or to its rapid 
elimination; and as antitoxin is absent, it seems likely that the im- 
munity rests upon an unreceptive quality in the cells of the body. 
Recent experiments have made it clear that toxins attach themselves 
closely to certain cells, as, for example, the nerve-cells in the case of 
tetanus; and it may easily be conceived that if these cells are not recep- 
tive, the toxin might circulate harmlessly in the serum. Experimental 
proof of this view will be cited later. 

The term antitoxin is applied to a substance or substances in the 
serum of an animal that protect against the toxin of a specific disease. 

Acquired Toxin Immunity. — -This condition was first explained by 
Behring in a manner similar to the explanation at that time offered 
for natural toxin immunity — that is, he taught that the tissues of 
the body become accustomed to the toxin, a sort of Mithridatization. 
Later he recognized that the resistance is due to the presence of an 
antitoxin. This at first was regarded by many as an altered form 
of toxin, and among other experiments offered to prove this view was 
•that of generating antitoxin in vitro by the action of either a continuous 
electrical current or a rapidly interrupted direct current. It is very 
likely, however, that the supposed antitoxin in this case was simply a 
toxin of lower virulence, and that its seemingly antitoxic character was 
really due to its capacity for developing immunity when injected into 
animals. 

Behring first produced antitoxin of diphtheria, but since his investi- 
gations antitoxins of tetanus, snake-venom, and of various infectious 
poisons, mainly of laboratory interest, have been produced. The pro- 
duction of antitoxin is accomplished by treating an animal at first with 
small, and later with larger, doses of the toxin until the antitoxic quality 
is developed. As a matter of practical procedure in some cases (e. g., 
diphtheria) cultures that have been sterilized by heat or cultures 
containing bacteria of low virulence are frequently used in the early 
injections, and later, when a certain degree of immunity has been pro- 
duced, the animal is inoculated with virulent cultures until the 
antitoxin reaches a maximum. When toxin of sufficient strength can be 
obtained, the antitoxin can be most surely prepared by using the toxin 
alone. 

18 



274 



A TEXT-BOOK OF PATHOLOGY 



Occasionally antitoxin is found in the normal animal or in man 
without previous occurrence of the infection under consideration; thus r 
in a notable proportion of normal horses, diphtheria antitoxin is found 
in the blood, and the same is true of children and of adult human beings. 
In the light of recent knowledge it seems probable that antitoxin may be 
produced by the cells under stimulation other than that of the specific 
toxin, and while antitoxins are specific to a very large degree, so that 
that of diphtheria protects only against the diphtheria poison and that of 
tetanus only against the tetanus poison, this specificity is not absolute. 
It is known that diphtheria toxin protects against abrin-poisoning, and the 
antitoxin of abrin protects against abrin- and ricin-poisoning, while the 
tetanus antitoxin is partially preventive against snake- venom. In other 
words, the blood has some natural antitoxic power which is increased as a 
non-specific body at the same time that specific antitoxins are being 
formed. Moreover, there are certain common constituents in various 
antitoxins that may possess a generic antitoxic power. 

Several years ago Theobald Smith showed that a nearly neutralized 
mixture of toxin and antitoxin produced a more lasting immunity to 
toxin than simple toxin. This has lately been put to practical use by 
Behring and his students. The loose chemical union of the two, 
formed in vitro, is broken up in part by the body, which then proceeds 
to form its own antitoxin. A too rapid effect of freed toxin is held in 
check by the accompanying antitoxin. 

Action of Antitoxin. — It was first thought by Behring that the toxin 
and antitoxin enter into a chemical combination which completely de- 
stroys the indentity of the two substances. This was disproved by the 
discovery that a mixture of snake toxin and its antitoxin, which ordi- 
narily has no effect when injected into an animal, becomes highly toxic 
when heated to 70° C. (158° F.). It is known that the antitoxin is de- 
stroyed at this temperature, while the toxin is not. It is very probable 
that the toxin and antitoxin enter into a form of loose chemical com- 
bination without losing their indentity, just as hydrochloric acid enters 
into loose combination with albumin in gastric digestion. 

The Chemical Nature of Antitoxin. — But little is known regarding the 
antitoxins excepting that they are relatively resistant to heat and other 
external agencies. Thus, the tetanus antitoxin bears a temperature of 
up to 70° C. (158° F.), as well as the action of sunlight, and even 
putrefaction, without being destroyed. It seems likely that the anti- 
toxins are albuminous bodies or that they are closely associated with 
such bodies. 

Transmission of Antitoxin. — The hereditary transmission of anti- 
toxin has been studied, and it has been found that transmission takes 
place from the mother to the offspring through the fetal circulation or, 
after birth, through milk. There is no transmission fron an immune 
male parent to the offspring. In experimental work the transmission of 
immune substance could not be traced as far as the second generation. 

Elimination. — Antitoxin is probably eliminated through all the 
secretory organs. It has been found in the urine and to a large extent 
in the milk. Brieger and Ehrlich obtained a quite concentrated form 
of antitoxin by precipitation of the globulin by ammonium sulphate 



BACTERIA, THEIR NATURE AND ACTION 



275 



and purification by dialysis. As in the case of toxins, the whole of 
the antitoxin seems to be carried down by the precipitated globulin. 

All the phenomena of immunity have been explained by Ehrlich 
in a very comprehensive theory called the side-chain theory. The 
applications of this to toxin immunity will be first considered for 
the sake of simplicity. 

Ehrlich's Side-chain Theory. — Toxin Immunity. — This theory 
explains the facts regarding the action of toxins and the formation of 
antitoxins better than any that has been suggested. It is based upon 
the hypothesis that bacterial toxins, like assimilated foodstuffs, enter 
into chemical combination with the cells of the body. In this respect 
toxins differ from ordinary poisons which do not enter into such com- 
bination, and this may explain the failure of all experiments at produc- 




Fig. 107. — Receptors of three orders (Ehrlich). 
Ehrlich has described receptors of three orders: 1, The receptor of the first order is a 
single combining group without any other function. On this account Ehrlich speaks of 
it as a uniceptor. In Fig. 107, J, such receptors are shown at a. On the right hand, the 
receptor has become united with a toxin molecule, b. The latter shows its haptophore 
group at c, and its toxophore group at d. It is the receptor of the first order that con- 
stitutes antitoxin when liberated from the parent cell. 2. Receptors of the second order 
(Fig. 107, II, c) have a haptophore group, e, and a zymophore group, d. The latter is so 
named because of its ferment-like capacities. On the right hand is seen a molecule of 
nutrient matter, /, combined with the haptophore group of the receptor, in such position 
that the zymophore group can act upon it. Having but one haptophore group, like the 
receptors of the first order, those of the second order also are included under the term of 
" uniceptors." The phenomena of agglutination and precipitation are probably occasioned 
by this second order of receptors. 3. Receptors of the third order (Fig. 107, III, 'i) carry 
two haptophore groups, e and g. One of these combines with a molecule or cell, ./, for 
which the receptor has affinity, and the other combines with the haptophore group of the 
complement, k, which, when so combined, can act upon the molecule anchored to the 
other haptophore group. The complement has two groups — one, its haptophore, h, and the 
other, its zymotoxic group, z. 

tion of antitoxins for such poisons. Some non-bacterial poisons, such 
as snake- venom, abrin, ricin, etc., resemble toxins in combining with the 
cells, and it is notable that in the case of these poisons antitoxins have 
been produced. The combination between a toxin and a cell is effected 
by atom groups or radicals (to borrow terms from organic chemistry), 
the group of the cell entering into combination with the group of the 
toxin. It is assumed that the body-cell is like a complex chemical sub- 
stance with unsatisfied bonds, to which is added power to combine 
with substances having affinity for it through these bonds, and to cast 
them off after this new combination is effected. These groups which 
effect the junction of the cell and the toxin are termed haptophore 
groups. In addition to its haptophore group, the toxin molecule con- 



276 



A TEXT-BOOK OF PATHOLOGY 



tains a toxophore group which carries the toxic capacities, but the toxo- 
phore group cannot operate upon a cell until the toxin has been anchored 
to the cell by the junction of the haptophore groups (Fig. 107). When a 
toxin is introduced into the body, it finds cells with haptophore groups 
having affinity for its own haptophore group. These haptophore 
groups of the cells, from their receptive function, are called receptors 
and they are specific in so far as the receptors of certain cells will 
combine with the haptophore groups for which they have affinity 
and with no others. In this way it may happen that a highly toxic 
body may circulate harmlessly in the body, as there are no receptors 
for which it has affinity. (This matter was referred to in the paragraph 
on Natural Toxin Immunity.) 

When the receptors of the cells are utilized by combination with the 
haptophores of the toxin they may be regarded as neutralized or practi- 
cally destroyed, and the cell has suffered a " defect" which must be re- 
placed by regenerative processes. This usually follows promptly, accord- 
ing to the well-known theory of Weigert that destruction is followed by 
regeneration. In accordance with the same theory this regeneration 
often more than replaces the loss, so that in the case under discussion 
there is an overproduction of receptors in the cell, and some of these are 
extruded from the cell into the blood-plasma. The actual extrusion or 
separation of the haptophore groups requires the stimulus of the toxo- 
phore group. The separated haptophore groups now free in the 
blood-plasma constitute the antitoxin, since they are now free and able to 
combine with the toxins before these can reach cells susceptible to the 
action of the toxophore group. The toxin thus combined with a liberated 
receptor (antitoxin) is incapable of harm, as its own haptophore group 
is promptly joined to the antitoxin and cannot, therefore, become an- 
chored to a vulnerable cell, which is the prerequisite for the operation 
of the toxophore group upon a cell. After antitoxin formation has 
begun, it may continue for some time, causing successive discharges 
of the antitoxin material into the blood-stream. This is shown by the 
continued presence of antitoxin in animals that have been bled so 
abundantly that practically all the original blood must have been with- 
drawn. 

All the steps in this theory have been practically demonstrated. 
In the first place, it has been shown that the toxin enters into firm 
combination with the cell by mixing tetanus toxin and emulsions of 
normal brain tissue. Under these circumstances a certain proportion, 
or all, of the toxin unites with the nerve-cells, and the mixture is found 
to be harmless when injected into animals. In the second place, it has 
been shown that the receptor formation results from the combination 
of the haptophore groups of the toxin and of the cell, and is independent 
of the toxophore group. This was demonstrated by producing increased 
susceptibility to the action of toxin in animals inoculated with toxoid 
(a body derived from toxin, but having no toxic qualities). The toxoid 
has the same combining capacity for receptors of the cells as has the 
toxin, but it simply lacks the toxophore groups, which somehow have 
disappeared or become altered. In the experiment just quoted there 
was no trace of antitoxin in the blood; hence the toxoid was capable of 



BACTERIA, THEIR NATURE AND ACTION 



277 



causing increased production of receptors on the cells, but not free in the 
blood as antitoxin. Other experiments show that the stimulus of the 
toxophore group is necessary to cause the separation of new-formed 
receptors from the cell. In the third place, it has been shown that the 
antitoxin formation takes place in the fixed tissue cells, where the toxin 
finds suitable receptors, and not in the circulating blood itself, since 
antitoxin could be extracted with salt solutions from the blood-making 
organs of animals that had been treated with toxin, but had not yet any 
antitoxin in the blood. Of course, the period of time during which such 
an experiment could succeed must be a very brief one, but it has been 
accomplished. 

Numerous experiments have shown that the antitoxin is not altered 
toxin, but a new production, as stated in this theory. The large amount 
of antitoxin produced by a small amount of toxin alone would suffice 
to disprove the theory of transformation. 




I TT 



Fig. 108. — I. Scheme showing cell with receptors (a) . One receptorhas been occupied 
by a toxin molecule (6). There has resulted an overproduction of receptors, and two of 
these (a') have become separated from the cell. 

II. Scheme showing toxin molecules (6) attached to free receptors (a') in the blood. 
The toxin is thus prevented from attaching itself to the receptors (a) of the cell, and the 
toxophore group (d) is harmless. 

Haptophore groups or receptors still in connection with the parent 
cell are not to be regarded as antitoxin; rather the contrary, for they 
serve to anchor the toxin to the cell where the toxophore group is in 
position to injure the cell (Fig. 108). The experiment quoted above 
showed this, for the animal treated with toxoid developed increased 
vulnerability to toxin (because of the increased number of receptors) 
and had no trace of antitoxin in its blood. It is only haptophore groups 
that are free in the circulation, and therefore capable of fixing toxin and 
keeping it away from the cells that constitute antitoxin. 

This antitoxin production Ehrlich ascribes to his uniceptors or 
receptors of the first order. It is the simple union of toxin haptophores 
and fixed or free cell receptors. 

Bacterial' Immunity.- — (a) Bacteral immunity as applied to agglu- 
tination and precipitation is next in order. These processes are ex- 
plained by Ehrlich' s receptor of the second order. This assumes that the 
cell receptor has two parts, one to combine with the haptophore of the 
bacterium or other body, the other a zymophoric part, to act upon the 
toxophoric part of the bacterium (see Fig. 107). 



278 



A TEXT-BOOK OF PATHOLOGY 



Agglutination. — Bacterial agglutination (Pfeiffer-Gruber-Durham 
phenomenon) is explained by Ehrlich 's theory somewhat in the same 
way as bacteriolysis and hemolysis. In the case of agglutination, how- 
ever, there is but one agent — a liberated amboceptor having a hapto- 
phore group, which attaches itself to the bacterium, and a zymophore 
group, which plays a part similar to that of the complement in bac- 
teriolysis (see Fig. 107, //, d). It differs from the complement, however, 
in that the zymophore group is an integral part of the amboceptor, and not 
a separate body, which attaches itself to the latter. A serum which has 
the property of agglutinating the bacteria of a certain disease (as e. g., 
typhoid fever) contains liberated amboceptors that were set free by 
the cells of the body and that have the property of attaching them- 
selves to the specific bacteria concerned in that disease. When so 
attached, their ferment-like group or zymophore group, which is the 
active agent, produces agglutination. The zymophore of the antibody 
is the agglutinating substance or agglutinin, while the corresponding 
fraction of the bacterium is the agglutinable body. This was mentioned 
on p. 272. (See also Typhoid Bacillus.) Agglutinins are also found in 
normal blood, although in but small quantity. They are thermostabile, 
and resist drying of the serum. 

Precipitin. — The phenomena of precipitation of various substances 
that have been introduced into an animal organism by the action of 
serum derived from the blood of such animals have been ascribed to 
specific " precipitins. " Thus, when the blood of human beings is repeat- 
edly introduced into the peritoneal cavity of rabbits, the rabbit-serum 
acquires the property of precipitating human blood. When the blood 
of several animals in succession is introduced into an animal of a differ- 
ent species from each of these, it is found that the precipitation is a 
specific process, since the specific power to precipitate the blood of each 
of the species employed can be successively demonstrated. When 
albuminous liquids or such a complex mixture as milk is introduced 
into animals, the blood-serum of the animals acquires the property of 
precipitating the albumin used or the milk (casein). This and other 
experiments show the Avide range of applicability of the principle of 
precipitation. Ehrlich explains the process of precipitation in the same 
way as that of agglutination, by the assumption that amboceptors 
carrying haptophore groups with an affinity for the precipitable body 
are set free in the serum, and that associated as an integral part of these 
amboceptors are zymophore groups capable of producing the phenomenon 
of precipitation or agglutination. The zymophore groups are destruct- 
ible by heat, though the degree of heat is much higher than that re- 
quired to destroy the complements concerned in bacterial destruction 
and hemolysis. 

-(&) Bacterial Immunity as Applied to Bacteriolysis and Cytolysis. — ■ 
The application of Ehrlich 's theory to the phenomena of bacterial 
immunity is quite as satisfactory as it is to the formation of antitoxins. 
When a bacterium is introduced into the body, the problem of the 
defence of the organism against the invading bacterium is much more 
complicated than that of the defence against a toxin, because the bac- 
terium contains a variety of substances, such as its protein and various 



BACTERIA, THEIR NATURE AND ACTION 



279 



ferments, and may elaborate specific toxins in the culture-medium. 
In consequence, the defence of the animal organism against the bac- 
terium is a complicated one, involving formation of antitoxin and 
other antagonistic bodies, including those which attack the bacterium 
itself in contradistinction to the products of the bacterium. The 
defense against the bacterium is the process that has been referred 
to previously in describing Pfeiffer's phenomena of bacteriolysis. This 
process, according to Ehrlich 's investigations, is practically indent cal 
with that of hemolysis, or destruction of red corpuscles, which occurs 
when the blood of one animal is injected into another, or when certain 
hemolytic agents, like snake-venom, are introduced into the blood. 
As the study of hemotysis is practically much easier than that of 
bacteriolysis, the theory was elaborated on the bases of experiments in 
hemolysis, and two distinct substances or bodies are involved in the 
process. One of these Ehrlich formerly designated as the intermediary 
body in the case of hemolysis, or the immune body in the case of bacterial 
immunity; the second is a complementary body, and is designated the 
complement. The intermediary body, or immune body, is a product of 
cell activity under the influence of infectious, toxic, or other agencies, 
which is set free in the same manner as the haptophore group or re- 
ceptor in the case of antitoxin formation. It has two haptophore 
groups — one having affinity for the complement, and therefore desig- 
nated complementophilic; and the other having affinity for the bacterium, 
red corpuscle, or other cell, and therefore designated cytophilic. On 
account of this possession of two haptophore groups Ehrlich later desig- 
nated the intermediary body by the term amboceptor. This is Ehrlich 's 
receptor of the third order. It is a stable substance, not influenced by 
moderate heat. The complement, on the other hand, is a ferment-like 
body, and is a constituent of normal blood-plasma. Its ferment-like 
character is evidenced by its ready destructibility by heat (55° or 56° C; 
131° or 132° F.). The origin of complement has been variously ascribed 
to leukocytes, lymph-glands, and liver. Without the complement the 
amboceptor is ineffective, and without the amboceptor the comple- 
ment cannot affect the cells (bacteria, red blood-corpuscles, etc.). The 
cytophilic group of an amboceptor is more or less specific, so that, unless 
the receptors (haptophore groups) of the bacteria, red corpuscles, etc., 
are homologous with the cytophilic haptophore of the amboceptor, 
combination will not occur — in other words, the amboceptors are more 
or less specific and must be homologous with the receptive haptophores 
or receptors of the cells. There must, then, be a great many varieties 
of receptors — -perhaps hundreds or thousands — in order to fix the equally 
numerous varieties of amboceptors, and the same is perhaps true of 
the complement. Various substances doubtless act as complements. 
Thus, in experiments on snake-venom, Kyes found that lecithin is the 
complement. 

The bacteriolysin of Buchner, called by him alexin, is, according to 
recent views, a compound substance, one part being the amboceptor, the 
other the complement. 

Explanation of Pfeiffer's Phenomenon. — The phenomenon of Pfeif- 
fer's bacteriolysis may be explained in the following manner: When a 



280 



A TEXT-BOOK OF PATHOLOGY 



bacterium, with a quantity of immune serum, is introduced into the 
peritoneal cavity of a non-immunized animal, amboceptors derived from 
the immune serum attach themselves to it. The complement present 
in the peritoneal fluid then becomes anchored to the complement ophilic 
haptophore group of the amboceptor, and in this position is able to bring 
about the solution of the bacterium and its destruction. The phe- 
nomena of hemolysis may be explained in the same way: the amboceptor 
first attaches itself to the red corpuscle, and the complement (hemolysin) 
in turn attaches itself to the amboceptor. 

The necessity for two bodies in the production of these phenomena 
has been thoroughly demonstrated. It is known that serum capable of 
producing Pfeiffer's phenomena in vitro loses this power when subjected 
for a certain length of time to heat or sunlight. A prompt restoration 
of the power follows the addition of small quantities of normal (unheated) 
serum of the same animal species. This proves that a ferment-like body 
(destroyed by heat) is a necessary factor, and that this ferment is present 
in the normal serum of the animal. The importance of the complement 



Fig. 109. — I. Diagram representing the amboceptor and complement free and attached 
to the cell by means of the appropriate receptor. II and III. Scheme showing (1) pos- 
sible antibodies; (2) anti-amboceptor; (3) anticomplement; both of these have been demon- 
strated as possible antibodies, a, Cytophilic group; b, complementophilic group. 

has been further demonstrated by the formation of anticomplements, 
which are capable of combining with it and thus stopping its action. 
When the anticomplement is withdrawn, the complement is again 
capable of operating. In a similar manner anti-amboceptors have been 
produced, and have sometimes been found in the blood of normal animals. 

The following scheme represents graphically the relations of the 
amboceptor and complement to the cell and the possibilities of the 
various antibodies, such as the anticomplement and anti-amboceptor 
(Fig. 109). 

Cytolysin. — Injections of emulsions of various cells into animals 
have been found to generate destructive substances in the serum of the 
experimental animals. These destructive bodies are specific for the cells 
used in the experiment. Thus, spermatolysin, epitheliolysin, and hep- 
atolysin are substances which will cause destruction of spermatozoa, 
epithelia, and hepatic cells respectively. The phenomena involved 
in such cytolysis are closely allied with those of bacteriolysis and 
hemolysis. 



free 
COmplemem 



free 
amboceptor 




BACTERIA, THEIR NATURE AND ACTION 



281 



The following tables (modified from Muller) will show in a con- 
densed form the varieties of immunity detailed in the foregoing 
paragraphs : 

Antitoxic Immunity 

I. Cellular. 

A. Lack of appropriate receptors. 

(a) Congenital. 

(b) Acquired (loss of the receptors). 

B. Lack of susceptibility to the toxophore group of the toxin. 

(a) Congenital. 

(b) Acquired (?). 

C. Attachment of the toxin to insusceptible tissues. 

(a) Congenital. 

(6) Acquired (development of new receptors in insusceptible tissues). 
II. Hematogenic. 

A. Active. 

(a) Manifest form (abundance of antitoxin in the blood). 

(b) Latent form (no antitoxin present, but capacity for making it 

quickly and abundantly). 

B. Passive. 

Antitoxin is introduced: 

(a) Through the placenta to the fetus. 

(b) Through milk to the nursling. 

(c) By direct injection. 

Antibacterial Immunity 

I. Natural (congenital). 

(a) The animal organism is an unsuitable medium for the growth of the 
bacterium. 

(b) The organisms are destroyed at the point of infection by amboceptors 
and complements (bacteriolysis). 

(c) Amboceptors present, but no complements. 
The latter are supplied by — 

1. Increased supply of tissue fluids. 

2. Advent of wandering cells. 

(d) Complement present, but no amboceptors. 
The latter are supplied — 

1. Locally. 

2. By the lymphoid blood-making organs. 

(e) Phagocytosis and intraphagocytic bacteriolysis. 

II. Artificially increased, but not specific (pseudo-immunity). Injection of 
irritating substances which cause local accumulation of phagocytes and 
bacteriolysins. 

III. Naturally acquired specific immunity. 

IV. Artificially acquired specific immunity. 

(a) Active immunity. 

1. Abundant presence of specific amboceptors in the blood and tissue 

fluids. 

2. No preformed amboceptors, but increased capacity to manufac- 

ture such, by prophylactic injection. 
(6) Passive immunity. 

Specific amboceptors in the blood (derived from another animal). 

Complement Deviation and Fixation. — When complement is bound 
in such manner that it cannot enter into combination with antigen and 
amboceptor in bacteriolysis or cytolysis, it is said to be " deviated" or 
"fixed." The terms, however, are used for slightly different conditions. 



282 



A TEXT-BOOK OF PATHOLOGY 



If more antibodies be employed in tests or injections than the antigen 
can use, the excess combines with complement and prevents it from 
acting with the antibodies bound to the antigen. This is complement 
deviation, and of slight moment here, except to be contrasted with 
complement fixation as a diagnostic procedure. If the serum of rabbits 
immunized against sheep erythrocytes be mixed with sheep red cells in 
the presence of complement derived from normal guinea-pig serum, 
hemolysis results. When, however, complement is absorbed, as now 
to be shown, hemolysis will not occur. A mixture of the serum of a 
person suffering from a micro-organismal disease, an emulsion of the 
causative microbe, and guinea-pig serum containing complement results 
in the solution of the germs, i. e., bacteriolysis, because the three factors 
— antigen, amboceptor, and complement — are present and are bound 
together. If, now, we were to add to this same mixture the antisheep 
cells rabbit serum and the sheep cells, no solution of the hemoglobin 
would result because the complement has been fixed by the first combina- 
tion. This is the principle of the Wassermann reaction in syphilis. It 
can be and is used chiefly for determination of the presence of anti- 
body in the blood of infected persons. The application to syphilis will 
be discussed later. We refer to works on immunology for deeper 
consideration. 

Anaphylaxis or hypersusceptibility is a condition of increased or 
altered susceptibility of the animal organism to foreign protein. In a 
sense, then, it is a condition opposed to immunity, although in some 
cases it may act to protect the body against infection. The term allergie 
has been suggested by von Pirquet to express the altered and usually 
increased property of the body to react to foreign protein. 

Hypersusceptibility may be natural or acquired. The former is 
exemplified by the susceptibility of certain persons to pollen in rose-cold 
and hay-fever, or to fish and oysters which is shown by skin eruptions. 
Acquired hypersusceptibility is expressed when the body, once having 
received a foreign protein, is exposed to it a second time. For example, 
if a guinea-pig receive a small dose of horse serum, no symptoms will 
arise, but when a somewhat larger second dose is given, after an incuba- 
tion period of eight to ten days, it will almost immediately become 
depressed and nervous, scratch its nose, develop violent dyspnea, and 
die; the fatal outcome occurs usually within an hour, but may appear in 
a few minutes. Upon postmortem examination there will be found spas- 
tic dilatation of the pulmonary alveoli of local and central origin, hemor- 
rhage into and ulceration of the gastric mucosa, and scattered petechial 
hemorrhages. The death is due to respiratory failure, as the heart 
continues to beat after respiration has ceased. This sudden and violent 
reaction is called "anaphylactic shock," a condition most clearly ex- 
pressed by the guinea-pig, which animal seems to exhibit the most 
pronounced reactions in allergie tests. Almost every animal, however, is 
capable of some form of anaphylactic reaction, and the symptoms, signs, 
and pathology are similar in all. The reactions differ in degree, of 
course, depending upon the amount and nature of protein injected, 
the incubation period, and the receptivity of the animal. If the amount 
of serum injected the second time into the guinea-pig be too small, or 



BACTERIA, THEIR NATURE AND ACTION 



283 



if introduced so that the absorption is quite slow, symptoms will be 
delayed, milder, and may not proceed beyond nervousness and scratching. 
Injection of a second dose of serum into a guinea-pig but within about 
five days of the first dose, throws the animal into a refractive state 
so that no symptoms appear upon a later injection at the end of the 
usual incubation period. If the dose be given into the skin instead of 
under it or into the circulation, only a local reaction of redness and edema 
may be occasioned. The injection first given is called the sensitizing 
dose; the second, the intoxicating dose. 

In the discussion of infection and allergie given below it will be seen 
that previous exposure to a protein (bacterial) acts as the first dose, while 
the place of the intoxicating dose is taken by the protein (bacteria) from 
which the infection immediately arises. 

Hypersusceptibility is specific, that is, an animal will be intoxicated 
only by the protein with which it has been sensitized. Guinea-pigs 
may be sensitized to several proteins and react specifically to each. 
The allergic state is transmissible to young from the mother only; if 
the father only be sensitized the offspring does not inherit the condition. 
During the anaphylactic reaction there will be found leukopenia with 
eosinophilia, lengthening of the blood coagulation time, a fall in 
blood-pressure, rapid weak heart action, lowering of temperature 
and dyspnoea. 

The allergic state is sometimes seen in human beings after the injec- 
tion of antisera, notably diphtheria antitoxin, the reaction taking the 
form of " serum sickness" or of anaphylactic shock. Serum sickness oc- 
curs after an incubation period of a week to ten days, and is character- 
ized by nervous depression, skin irritation, urticarial eruptions, fever, 
and malaise; occasionally the condition may be quite severe, appearing 
like an acute general infection. Anaphylactic shock in human beings 
after serum injections is similar to that outlined for guinea-pigs, and 
death may ensue in a few minutes. The vast majority of cases in which 
this acute reaction has been observed have suffered from asthma. In 
this connection an explanation has been sought in the fact that the 
anaphylactic reaction sets up spasm in involuntary muscle; that the 
muscles of the bronchi are contracted and shut off the alveoli. 

As has been suggested before, anaphylaxis may explain some cases 
of asthma. Recent work has clearly shown that the eating of certain 
foods (eggs, wheat, pork) or exposure to plants (pollinosis) or, to the 
emanations from animals (horse hair or dandruff, guinea-pig hair or 
dandruff) are responsible for the disease, a conclusion strengthened by 
observing the absence of attacks when affected persons are no longer 
subject to the action of the substances mentioned. 

Allergie also explains the responses obtained when the skin of a 
person suffering from an infectious disease is inoculated with some of the 
virus of that disease. This phenomenon is exemplified by the skin 
reaction against tuberculin exhibited by the tuberculous, and the luetin 
reaction in syphilitics. It is a local manifestation of general anaphylaxis. 

There is a general tendency now to use this anaphylaxis, or the allergic 
state, to explain the contraction of infectious disease. It is assumed that 
when a person contracts such a disease he has been susceptible to the 



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organism as an individual peculiarity, or has been prepared, sensitized, 
in some way. Arguing also upon the known power of foreign protein 
to cause parenchymatous degeneration it has been thought that certain 
parenchymatous inflammation might arise by acquired poisoning or by 
injection of sera. Furthermore the repeated injection of or infection 
with these substances might, it has been conjectured, result in such 
marked parenchymatous damage as to lead to connective tissue over- 
growth, in the nature of chronic inflammation or general fibrosis. 

One explanation of this phenomenon asserts that the body is unpre- 
pared for protein introduced at other places than the alimentary tract, 
and must prepare a ferment against it. This it does after the first dose, 
but in accord with Weigert's overproduction theory, it produces a 
superabundance of this ferment, which, when acting upon the second 
dose, breaks it up so quickly that various digestion products are thrown 
on the organs suddenly and poison them. Another theory assumes that 
toxic protein circulates in the blood after the first dose; the body cells 
are poisoned by it, but gain an affinity for it, so that they attract it in 
large quantity after the second injection, being then fatally injured. 
Friedberger views the anaphylactic reaction as the effect of toxic pro- 
teins upon cells through their sessile receptors, thus permitting a direct 
injury to the cell protoplasm. It is not until several injections have been 
given that receptors are freed and combine with toxic substances, apart 
from cells. This is in accord with Ehrlich's theory that cells are vulner- 
able in proportion to the number of their sessile receptors. Friedberger 
has used the principle to develop his anaphylotoxin theory of infection. 
He assumes that an organism circulating in the body combines with the 
antibodies it has stimulated. This combination is then rendered toxic 
when acted upon by complement. 

Jobling goes further than this, asserting that antigens absorb the 
unsaturated fatty acids of the blood, which hold in check the tryptic 
power of the serum, permitting the serum to break up bacterial and 
natural proteins (the animal's own tissues supplying the protein to be 
broken up) and allowing escape of their toxic elements. According 
to this author and his associates, shock results from a mobilization of 
non-specific protease, and a decrease of antiferment by adsorption or 
by colloidal changes in the antigenic or native protein, causing a cleavage 
of serum proteins through the peptone to the amino state, resulting in 
an intoxication of the body cells by the last ; this seems to be evident by 
an increase in the serum lipase. They are sure that the antigenic protein 
is not the basis of the intoxicating amino nitrogen as it will not supply 
as much as can be found in the blood during the period following shock. 
Bronfenbrenner likewise believes that body or serum proteins not the 
antigen, supply the substrat to be broken up. 

Vaughan believes that the invasion of the body by bacteria stimu- 
lates a ferment which, acting upon the organisms, frees their toxic pro- 
tein. The ferment is specific for the infecting germ and will react 
quickly when this enters the body the second time. The toxic fraction 
of all bacteria is the same. He explains infection and allergie on this 
basis. The specific antibodies are stimulated by the specific protein, 
so that typhoid bacilli have their own, pneumococci theirs, etc. It 



BACTERIA, THEIR NATURE AND ACTION 



285 



certainly seems that the anaphylactic state is due to degradation products 
of proteins and that the substances giving rise to it are complex proteins. 
The body fluids seem to react to the parenteral introduction of proteins 
by adjustments tending to break down these substances into simpler 
combinations like the amino-acids. Abderhalden has shown that in 
the serum of pregnant women there are ferments capable of digesting 
placental tissue, but later researches have thrown some doubt upon 
the specificity of the test. Judging from the facts given in the fore- 
going paragraph, it would seem that there are easily available ferments 
which could destroy foreign protein such as the placental cells. 

Novy however has concluded to look upon anaphylaxis as not re- 
lated to immunity but as akin to coagulation, believing, as in this process, 
the matrix to be constantly present in the blood and " ignited" by many 
substances (bacteria, cells, agar, kaolin, silicic acid and many others). 
The action of the igniting substance is catalytic and its result is the 
formation of a toxic substance like anaphylatoxin, which is not clear in 
origin but is in all probability a tautomeric change in the matrix; this 
substance is quite labile. Specificity depends not upon the protein from 
which the toxin is formed but upon the catalyzer. He has found also 
that alkali destroys the anaphylatoxin formation in the test tube and 
gives encouraging results clinically. He proposes further that the names 
taraxigen be substituted for antigen, taraxin for the matrix and taraxy 
for anaphylaxis. 

Chemistry of Antigens and Immune Bodies.— The exact com- 
position of the various elements that have been brought to light by 
immunity researches is not known. Some observers maintain that only 
proteins can give rise to the immunity phenomena, but others believe that 
some lipoids and glucosids can act as antigens. No substances simpler 
in composition than peptones seem able to act as antigens. Judging 
from the work of Vaughan and Abderhalden upon bacterial and other 
protein intoxication, the defenses of the body seem all to be directed 
against foreign protein. These proteins are specific, in that protection 
or susceptibility toward one will not protect or dispose toward another. 
The various substances in the serum involved in immunity or allergie 
are precipitated with protein fractions, seem inseparable from them, 
and cannot be obtained in a pure state but each protein part of a sub- 
stance like serum can act as antigen and Wells has shown that specificity 
depends upon the identity of the protein molecule. The method of 
action, be it chemical, mechanical, or electrolytic, is not known. 
It might be well to emphasize here that in speaking of this parenteral 
introduction of protein a substance foreign to the tissue is implied. 



CHAPTER IX 



DISEASES DUE TO BACTERIA 

The bacterial diseases form a large and increasing group. In some 
cases it has been shown by the positive application of Koch's rules 
(see p. 39) that the suspected micro-organisms are the actual causes 
of the diseases under consideration; in more numerous instances all 
of the rules cannot be applied, but other considerations go far toward 
establishing the specific nature of the suspected bacteria; in still other 
cases the evidence warrants a strong suspicion of the pathogenicity of 
bacteria found in connection with certain diseases, but there is nothing 
approaching actual demonstration. 

Diseases Due to Cocci 
suppurative diseases 

Definition. — Under this heading we include for the present various 
forms of suppurative inflammation, such as furunculosis, abscess 
formation, and allied diseases, like osteomyelitis, endocarditis, cellulitis, 
etc. 

Etiology. — Numerous organisms have been found to have the power 
of producing suppuration ("pyogenic organisms). Among these the 
staphylococcus group is most important. The Streptococcus pyogenes, 
seu erysipelatis is also of great significance; less frequently the Diplo- 
coccus pneumoniae, the pneumobacillus of Friedlander, the Bacillus 
pyocyaneus, the typhoid bacillus, the Bacillus coli communis or the 
Bacillus pyogenes foetidus, the gonococcus, and others. Some cases of 
suppurative disease are due to a single organism; in many there is 
double or multiple infection. 

1. The Staphylococcus Group. — Among these have been described 
three important forms: the Staphylococcus pyogenes aureus, albus, and 
citreus. 

The Staphylococcus pyogenes aureus is a minute, rounded body 
about 0.5 to 1 ju in diameter, having no motility and not forming 
spores. When found in the tissues the cocci are apt to be associated in 
clusters, whence the term ''staphylococcus." Sometimes they are grouped 
in pairs, and may thus present a resemblance to gonococci. The op- 
posed surfaces, however, are flat instead of concave, as is the case with 
the gonococci. The staphylococcus may be stained with ordinary anilin 
solutions and is beautifully demonstrated by Gram's method. Cul- 
tures are easily obtained upon the ordinary media. The most charac- 
teristic growth is that upon agar. Along the line of inoculation a moist 
colony develops, with at first a whitish but soon an orange-yellow color, 
especially under the influence of light. The growth in gelatin causes 

286 



DISEASES DUE TO BACTERIA 



287 



rapid liquefaction and the precipitation of orange-yellow particles. 
The growth is best obtained at oven-temperatures (25° to 35° C; 
77°-95° F.), but may be secured at lower degrees. 

Distribution. — The Staphylococcus aureus is frequently found upon 
the skin or in the various external secretions of healthy individuals. 
It does not seem to nourish anywhere apart from the bodies of men or 
animals, but may remain in an active state in the dust of rooms or 
upon clothing and the like. It has been found in various lesions of the 
body, notably, however, in furuncles, abscesses, and carbuncles, and in 
ulcerative conditions of the exterior or of the mucous membranes. It 
is also frequent in internal suppurative inflammations, such as malig- 
nant endocarditis, osteomyelitis, appendiceal abscesses, etc. In many 
of these lesions other organisms may be associated. 

Pathological Physiology. — Filtrates of the cultures and the bodies of 
the staphylococci (killed by heat) contain highly toxic substances 
capable of producing intense inflammation and suppuration. Certain 
of their products are markedly hemolytic. 

When injected into the subcutaneous tissue the staphylococcus 
produces local effects. The organisms may become liberated, gain 
entrance to the circulation, and produce widespread results; but it does 
not seem to produce extracellular toxins that cause generalized results. 
The effects of the staphylococcus seem to be due rather to a certain 
poisonous body contained in the organism itself. This has been termed 
"bacterial protein," and it has been thought to belong to the group of 
alkaline albuminates. This body by its chemotactic effect causes the 
leukocytic accumulations found in suppurative inflammations. The 
staphylococcus also leads to liquefaction in the tissues, as in gelatin, 
both directly and through the accumulation of bodies derived from 
leukocytes. The defence of the organism against the staphylococcus is 
partly mechanical and partly vital. The leukocytes probably englobe a 
certain number of organisms and cause their destruction, while soluble 
bactericidal bodies seem to be produced in the course of the infection. 

Injection of cocci gives rise to antibodies — agglutinins, opsonins, and 
bacteriolysins. Upon them depends the use of bacterin or vaccination 
treatment. 

Pathogenicity. — 'When virulent cultures are injected into animals, 
abscesses are produced and a fatal termination may follow. In the latter 
case dissemination through the blood is found, and infarcts of the kid- 
neys, lungs, and other organs caused by bacterial emboli are discovered. 
Multiple abscesses may be seen. The organism readily loses its virulence, 
as in the case of those found upon the skin of healthy persons and in 
other accidental situations. When rubbed in a virulent state into the 
skin of man it produces abscesses or boils. It may remain dormant 
within an enclosed abscess or sequestrum in a bone, or apparently in a 
subacutely inflamed heart valve or muscle, and light up upon some 
secondary infection. Staphylococcus infection tends to remain local, with 
occasional spread to the circulation. Its local lesions are of slower pro- 
gression than those of the streptococcus, and it seems at times to acquire 
the power of establishing foci or nests from which it sneaks in small 
numbers into the blood stream to settle upon some receptive serous or 



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A TEXT-BOOK OF PATHOLOGY 



mucous membrane; in other words, it takes part in what was discussed 
under focal or subinfection. Its presence sometimes favors the growth 
of other organisms, notably the influenza bacillus. 

Staphylococcus pyogenes albus (Fig. 110). — This organism is prac- 
tically identical with the last-named in morphology, but in culture 
produces a white instead of a yellow growth; usually it is less virulent 
than the golden variet}^ but this does not always hold good. One of its 
forms has been found as a frequent parasite of the skin (Staphylococcus 
epidermidis albus of Welch), only occasionally being of importance as 
the excitant of stitch abscesses. 

Staphylococcus pyogenes citreus. — This form is the least important 
of the three. It is not so common and, as a rule, less virulent. It differs 
in the brilliant lemon color obtained upon culture in various media. 




2. The Streptococcus pyogenes seu erysipelatis. — Under the name 
streptococcus are included various spherical bacteria which divide only 
in one plane and form chains of varying length. The different forms 
resemble each other so closely that some authors group them all, includ- 
ing the Streptococcus pneumonioe, under one general head. The last, 
however, seems sufficiently differentiated to merit separate classification. 

The Streptococcus pyogenes was first studied by Rosenbach in cases 
of suppuration. A similar organism was afterward described as the 
Streptococcus erysipelatis by Fehleisen. It would seem, however, that 
these two organisms are identical. The streptococcus is a small spherical 
organism of variable size (0.5-1 /*), frequently associated in chains of 
from three to twenty or more individuals (Fig. 111). Not rarely it 
occurs in diplococcus forms (as pairs). It is easily stained with ordinary 
anilin solution or by Gram's method. The cocci are not motile. Spore 
formation has not been observed, but occasionally in chains one of the 
individual members is larger than the rest, suggesting arthrospores. 
Upon artificial media scanty but rather characteristic growths are ob- 
tained. On the gelatin plate there are formed small, translucent, whitish 
or yellowish colonies of irregular outline. The gelatin is not liquefied. 
Upon agar a very thin, transparent growth forms around the line of 



DISEASES DUE TO BACTERIA 



289 



inoculation. It consists of separate colonies which usually do not 
coalesce. On mixed agar and blood plates the colony of the true strep- 
tococcus produces a pale gray dot surrounded by an area of hemol- 
ysis. Certain varieties lack this power. In milk the growth is usually 
abundant and attended with lactic acid formation and coagulation of 
the casein. 

In the genus Streptococcus there are several varieties that have been 
found so frequently under special conditions that they seem worthy 
of separate mention. The principal variety is termed Str. hemolyticus 
or longus because of its power to hemolyze red blood cells easily and its 
tendency to grow in long chains. The next one in importance is the 
Streptococcus mitior or viridans, which is common in streptococcal en- 
docarditis. It is not hemolytic and grows in green colonies on blood-agar. 
Streptococcus mucosus is a mucus-producing organism found usually in the 
throat or in enclosed abscesses. The name Str. epidemicus has been 
given to that form frequently found associated with groups of cases of 
sore throat disseminated by milk; it varies in certain chemical reactions 
only and can cause the usual streptococcal disease. The streptococci 
of the feces have minor peculiarities differing from the true type. Another 
variety seems to have a predilection for joint cavities {Streptococcus 
rheumaticus) . 

It has been asserted by Rosenow that the members of the strepto- 
coccus-pneumococcus group are but variants of one species, and he 
claims to have been able to follow a mutation from one to another 
under artificial conditions. Under prolonged artificial cultivations these 
organisms do surely lose some minor characters, but mutation must be 
stationary to be actual. 

The distribution of the streptococcus is much the same as that of 
the staphylococci, though it is less commonly discovered about the 
healthy body. It may, however, be found upon the mucous membranes 
or in the various secretions or excretions of the body. It is probably a 
strict parasite, multiplying only within the living organism. ■ 

In disease it has been found in various forms of suppuration, such 
as phlegmonous forms of inflammation of the subcutaneous or sub- 
mucous tissues, conspicuous examples of which are operation and autopsy 
infections and the spreading phlegmon of compound fractures and 
lacerated wounds, from both of which a generalized septicopyemia only 
too often results. It occurs occasionally in focal suppurations, such as 
abscesses, though these are more commonly due to staphylococci alone. 
The streptococcus occurs at times in ulcerative endocarditis, the character 
of the valvular change being slightly different according to the kind of 
streptococcus; the clinical course is decidedly different. The Str. hemo- 
lyticus usually produces a rapidly growing, spreading, and ulcerating 
vegetation on any valve it attacks, accompanied by symptoms of a 
severe infection leading to death after a short course. The Str. vivi- 
dans causes a disease of less active nature characterized by remissions 
suggestive of healing but followed by clear cut exacerbations; the 
outcome is, however, nearly always fatal. The valvular lesions, often 
limited to the mitral, take the form of small, flat, firm, gray-green 
masses at the base or on the mural endocardium. 

19 



290 



A TEXT-BOOK OF PATHOLOGY 



The generalized septicemia arising from streptococcus infection 
shows after death most characteristically numerous small hemorrhages 
arising where the organisms have caused thromboses of small vessels. 
There are apt to be also areas of blood stained edema, or this may be 
accompanied by leucocytic infiltration with the formation of a phlegmon. 
All parenchymatous organs, notably the heart, kidney and liver, show 
cloudy swelling. 

Streptococcic inflammations of the throat are of great interest. 
They may occur in persons previously in good health, or in the course of 
infectious diseases, like scarlatina, measles, or influenza. To the clinician 
the resulting lesion may be indistinguishable from that of diphtheria; 
bacteriological examination alone serves to establish the diagnosis. 
The lesion, while at first superficial, may penetrate the tonsil causing 
internal suppuration whence it may invade the blood stream. Local 
spread may occur via the Eustachian tube to the middle ear, causing 
otitis media, or into the soft tissues forming the floor of the mouth 
producing Ludwig's angina. The lesions in erysipelas consist of ede- 
matous infiltrations of the corium, accompanied by an increase in 
mononuclear cells, with a few chains of streptococci scattered about the 
spaces and crevices. 

Pathological Physiology and Pathogenesis. — The streptococcus seems 
to be more active in the production of soluble toxins than staphy- 
lococci. The toxin has been made by inoculating small quantities of 
bouillon with virulent cocci, allowing these to grow for several weeks, 
and then destroying the organisms by heat. The injection of the toxins 
thus produced leads to local and general reaction. While there is a 
certain amount of this extracellular toxin, it seems that most of the 
toxic substances of streptococci are embodied in the micro-organism 
itself. In virulent cultures actively hemolytic bodies are often present, 
and certain streptococcic infections in man are attended with hemor- 
rhages and evidences of hemolysis. 

The principal pathological character of streptococcal infections is their 
spread. Instead of localizing like the staphylococcus, a diffuse spreading 
inflammatory edema results with involvement of lymphatics and blood- 
vessels, by either of which routes the cocci get into the blood-stream. 
Serous membranes are especially susceptible to streptococci, and throm- 
bophlebitis or arteritis is the first lesion arising when the germ reaches 
a vessel. In these infections there is more often bacteremia than is the 
case with staphylococci. While on the whole streptococcus disease is 
relatively acute and limited, there is reason to think that it may play 
a part in subinfection or focal infection. The "mitis" variety is not 
uncommonly found in pyorrhea alveolaris and in this locality has been 
thought to play some role in the causation of chronic infective arthritis. 
That foci within tonsils may have something to do with heart and kidney 
disease is not impossible. 

Injected into animals (intravenously) virulent streptococci may 
occasion septicemia, but it is notoriously difficult to obtain cultures 
of great virulence and the succeeding generations soon lose their power. 
White mice and rabbits are the most susceptible animals. 

A single attack of erysipelas or streptococcic infection confers no 



DISEASES DUE TO BACTERIA 



291 



immunity on man and, similarly, one inoculation occasions no immunity 
in animals. By repeated injections, however, an antistreptococcus serum 
of some potency has been obtained. Recent studies show that more 
satisfactory practical results may be obtained when the antistrepto- 
coccus serum has been prepared with a strain of organisms similar to that 
present in the case under treatment. For this reason mixtures of serum 
prepared with several strains are used (polyvalent sera), so that in a 
clinical case (because of the difficulty in distinguishing various strains) a 
specifically active antiserum may be administered. From recent studies 
it would seem that whatever antibodies are present deteriorate with age 
and we have had some encouraging results with freshly separated serum, 
that is prepared for use within twenty-four hours after withdrawal from 
the horse. 

Streptococcus intracellularis meningitidis (Weichselbaum) . — This 
organism, also called meningococcus or Diplococcas meningitidis, is found 
in the meningeal pus, in the blood, nasal mucus, sputum, and urine of 
individuals affected with epidemic cerebrospinal meningitis. This 
micro-organism in some respects resembles very closely in its form and 
intracellular occurrence the gonococcus. 

The organism appears as a biscuit-shaped diplococcus, irregular in 
size, sometimes occurring as tetrads or in clumps, and occasionally as 
short chains in which the line of cleavage between the diplococci is in 
the same direction as that of the chain. The coccus is Gram-negative, 
but here and there will be found a few units that retain the blue of 
the gentian- violet. It is easily stained with Loffler's methylene-blue. 

In the meningeal exudates it is usually found within polymorpho- 
nuclear leukocytes, like the gonococcus. Some have described its 
occurrence within the cellular nuclei; this is doubtful. 

It grows well at 37.5° C. (100° F.) on blood-agar, serum-agar, and 
plain agar. On the latter there appear, in forty-eight hours, flat, 
grayish-white, faintly granular and viscid colonies that do not coalesce. 
On blood-agar the colonies are more luxuriant. 

Distribution. — The meningococcus is found in the seropurulent 
exudate of epidemic cerebrospinal meningitis and is readily demon- 
strated in the fluid obtained by lumbar puncture. It has frequently 
been found in the nasal mucus of patients suffering from the disease 
and in healthy individuals more or less closely associated with the 
patient. The assumption is, that the meningeal infection occurs by 
passage of the organisms through the lymph-channels from the nose 
or sinuses adjacent to the meninges. Recent experiments seem to 
indicate that the organisms may travel in the opposite direction, for in 
monkeys infected by intradural inoculation the organisms were found 
in the nasal cavities after a short interval. During epidemics some cases 
have been noted in which the meningeal symptoms appear after an illness 
of several days during which time it is claimed that meningococci can be 
found circulating in the blood. It is thought by some observers that this 
should argue in favor of the idea that meningococcus disease is primarily 
a general infection with secondary predilection for the coverings of 
the central nervous system. However, most instances of this infection 
are ushered in by rapidly developing symptoms pointing to the 



292 



A TEXT-BOOK OF PATHOLOGY 



meninges and the cases just mentioned represent a small percentage of 
the total. At the height of severe cases there is always a bacteremia. 
Organisms resembling the meningococcus and probably actual meningo- 
cocci have been found in the lungs in cases of bronchitis and pneumonia 
complicating epidemic menir gitis. Disease of the small vessels is common 
in infection with this bacterium, so that petechial or even larger purpuric 
spots are seen upon cutaneous, mucous and serous surfaces, whence the 
term "spotted fever." Endocarditis and arthritis are not uncommon 
complications. 

Pathological Physiology and Pathogenesis. — 'Large subcutaneous in- 
jections may cause death, and intrapleural and intraperitoneal injec- 
tions may kill animals and cause a fibrino purulent inflammation of the 
serous membrane. Subdural inoculation (spinal and cerebral) in dogs 
and monkeys have caused lesions indentical with those found in man. 

The toxins of the meningitis coccus are endocellular and are freed in 
vitro by autolysis. Agglutinins and lyins are developed in patients and 
experimental animals. The repeated injection of horses with menin- 
gococci will be followed by the production of agglutinating, lytic, and 
protective antibodies so that the serum can be used in therapeutics. It is 
commonly introduced directly into the subarchnoid space by lumbar 
puncture, after withdrawal of some cerebrospinal fluid, but it is also wise 
to administer a quantity into the vein to combat any existing bacteremia. 
Recent studies seem to indicate that there are at least two varieties of 
the meningitis coccus, differing only in their serologic properties, but 
this is important in serotherapy for both of them must be used in the 
production of useful antisera. 

Other Organisms in Meningitis. — The pneumococcus, Streptococcus 
pyogenes, Staphylococcus pyogenes, typhoid and colon bacilli, influenza 
bacillus, and, less commonly, some other forms have been isolated in 
cases of primary meningitis or meningitis secondary to infection else- 
where. 

GONORRHEA 

Definition. — Gonorrhea is an infectious inflammation of the urethral 
or other mucous membranes due to a specific organism, the Micrococcus 
gonorrhoea! or gonococcus discovered by Neisser in 1879. 

Etiology. — -There is no doubt that the gonococcus is the specific 
cause of gonorrhea. This organism is a micrococcus, usually arranged 
in pairs, the opposed surfaces of each being slightly concave. This 
arrangement has suggested the designation "biscuit-shaped" diplo- 
coccus (Fig. 112). Sometimes groups of four or more are found, while 
in other cases the cocci occur singly. The organisms are abundant 
in the pus of acute gonorrhea, less abundant in advanced stages, in the 
pus of gonorrheal salpingitis or other conditions, and may not be dis- 
covered at all. They generally occupy the pus-cells, lying in the proto- 
plasm, either in small numbers or so abundantly as to fill the cell 
uniformly. In the tissues the same intracellular position is usual, but 
here, as in the free pus, some organisms may generally be found between 
the cells. The gonococcus. stains readily with ordinary solutions of anilin 
dyes, and is distinctly Gram-negative. 



DISEASES DUE TO BACTERIA 293 

Cultivation of the gonococcus is difficult. Growths may, however, 
be obtained at 37° C. (98 . 6° F.) upon agar-agar streaked with human 
blood or on media prepared from human ascitic or pleuritic fluid or 
albuminous urine. Later generations may grow well on ordinary media, 
but usually require the serum additions. The growth in blood-serum 
consists of small colonies of grayish color that coalesce and form a film 
on the surface of the medium; around the colony may generally be 
seen an irregular and inconspicuous 
extension. 

The gonococcus cannot be posi- 
tively distinguished by its morphology 
nor by the intracellular position. 
Other organisms may in certain stages 
of their growth show a typical biscuit 
form (staphylococci and others) ; and 
the intracellular position is not rarely 
assumed by a variety of bacteria. 
The failure to stain by Gram's method 
and the failure to grow on ordinal 
media are strong points suggesting 
the gonococcus. Typical cultures 

alone establish the diagnosis. A Fig. 112.— Pas from gonorrhea, showing 

number of organisms resembling the gonococci (Jakob), 

gonococcus were found by Bumm in 

the vaginal mucus. The Micrococcus catarrhalis also resembles it 
closely. No similar micrococcus has thus far been found in the male 
urethra. 

Pathogenicity. — -It has been demonstrated ' by direct implantation 
of pure colonies upon the healthy urethra that this organism will cause 
characteristic gonorrhea. Urethritis may, however, be due to other 
organisms; the specific form termed " gonorrhea" is probably always due 
to the gonococcus. Secondary lesions, such as salpingitis, oophoritis, 
arthritis, peritonitis, conjunctivitis, endocarditis, etc., may also be due 
to this organism, no other form of bacteria being present. Sometimes, 
however, complications, such as periurethral abscesses, suppurative 
adenitis, etc., are due to secondary infections. 

Gonococci stimulate the formation of slight amounts of agglutinins, 
opsonins, and bacteriolysin. Antisera are of little value, but bac- 
terins or vaccines may be useful. The toxin is intracellular. 

Pathological Anatomy. — The lesions of gonorrhea will be con- 
sidered elsewhere. Suffice it to say in this place that the organism causes 
suppurative catarrh of the mucous surfaces with which it comes in contact. 
There is abundant cellular exudation and the organisms tend to pene- 
trate deeply into the tissues. 

Pathological Physiology. — Gonorrhea is in most cases a purely local 
disease. Little is known of its power to produce soluble toxins. The 
effects are probably due to an intracellular toxin. The distant lesions 
are in all cases, as far as we definitely know, dependent upon trans- 
portation of the specific . organism. These have been found in the 
effusions of arthritis, in meningeal exudates, and in the vegetations 




294 



A TEXT-BOOK OF PATHOLOGY 



of gonococcal endocarditis, as well as in the blood in the last-named 
condition. 

CROUPOUS PNEUMONIA 

Definition. — There are a number of forms of inflammation of the 
pulmonary tissues to which the term " pneumonia 7 ' is applicable. The 
most definite form of disease is that spoken of as croupous, fibrinous, or 

lobar pneumonia. In its typical 
form this is a specific and well 
characterized disease. It is in- 
fectious, more or less contagious, 
and caused by a specific organism. 

Etiology. — The organism most 
frequently found in the lung in 
croupous pneumonia and doubtless 
the specific cause of the disease in 
such cases is the Diplococcus pneu- 
monia?, belonging to the genus 
Streptococcus. It is less regularly 
the etiological agent in broncho- 
pneumonia and atjrpical pneu- 
monias, but even in these cases it 
found more frequently than 



Fig. 



113. — Diplococcus pneumoniae in the 
blood (Frankel and Pfeiffer). 



IS 



therefore, 



other bacteria. 

The organism is also called the 
pneumococcus, the Micrococcus lanceolatus, and sometimes the Strepto- 
coccus pneumoniae seu lanceolatus. The diplococcus of pneumonia was 
recognized in the saliva of healthy persons by Sternberg and Pasteur, 
but its relation to croupous pneumonia was first demonstrated by 
Frankel, and later by Weichselbaum. The individual organism 
has a somewhat elongated, lanceolate shape, and has 
been considered a bacillus, though it does not always 
show this pseudobacillary shape distinctly (Fig. 
113). In the sputum and lungs and in the blood 
of inoculated animals it is commonly found in 
pairs; the broader ends of the organisms adjacent, 
and the pointed ends projecting outward; the 
group is surrounded by a transparent capsule, 
which does not readily take stains, and therefore, 
becomes conspicuous (Fig. 114). Sometimes the 
organism forms chains, in which, however, the pairs 
of micrococci are a little distance apart. Chain 
formation is especially marked when the organism 
is grown in fluid media. The capsule is not seen 
when the organism is obtained from cultures. 
The diplococcus does not possess individual motility and has no flagella. 
It does not produce spores. 

It may be readily demonstrated in the sputum or in the tissues by 
staining with the ordinary anilin dyes or by Gram's method. 

Cultivation. — The diplococcus grows readily upon ordinary media, 
excepting potato. It forms characteristic colonies upon agar plates 




Fig. 114. — Diplococ- 
cus pneumoniae: a, 
Cocci, without capsules ; 
b, single and paired 
cocci, with capsules; c, 
chain form; d, colony 
of cocci (Ziegler). 



DISEASES DUE TO BACTERIA 



295 



or in gelatin. Upon the surface of the agar there appear transparent 
drop-like colonies hardly visible to the naked eye, which under the 
microscope have a finely granular appearance. Upon gelatin plates 
similar growths are produced, while in gelatin punctures the growth 
occurs along the path of the wire as granular whitish spots separated 
from each other. The addition of serum or ascitic liquid to agar makes 
a medium in which larger and more conspicuous grayish colonies of 
circular outline appear on the surface. In the paler marginal zone of 
the colony, diplococci or short chains may be seen. On blood-agar 
pneumococci produce small round greenish colonies without hemolysis. 
In bouillon a cloudiness is produced when the culture is from twelve to 
twenty-four hours old; later the organisms precipitate and the bouillon 
becomes clear. Milk is acidified and at times coagulated by the pneu- 
mococcus. When inulin is added to a serum medium the pneumococcus 
ferments the inulin and coagulates the serum. The organism tends to die 
out very readily in cultures, and also loses its pathogenic property when 
propagated for several generations. In solid media containing serum 
and more particularly in fluid media the virulence may be preserved for a 
long time, sometimes for months. It is most luxuriant at 37° C. (98.6° 
F.). Pneumococci are dissolved by bile or solutions of its salts, in this 
being different from the streptococci. 

Pathogenicity. — 'Recent studies have satisfied the postulates of Koch 
and these combined with immunological research and statistics have con- 
victed the pneumococcus as the cause of pneumonia. The diplo coccus is 
frequently found in the saliva of healthly persons. When this is intro- 
duced into animals, particularly, rabbits, the animal dies, with evidences 
of rapid sepsis (sputum septicemia). The postmortem shows some fibri- 
nous exudate and occasionally a little pus at the point of inoculation. The 
spleen is enlarged, and capsulated bacteria of distinct lanceolate form are 
widespread throughout the body. Injections of lung tissue or of pneu- 
monic sputum produce similar results, and the organism in pure cul- 
ture likewise causes this form of septicemia. It has been shown that 
injection of pneumonic exudate aspirated from the consolidated lung 
into the lungs of rabbits will produce true pneumonia. Typical 
pneumonia has been produced by injection of virulent pneumo- 
cocci into the lungs of rabbits previously immunized against the 
pneumococcus to prevent the occurrence of general pneumococcus 
septicemia. The most successful attempts at producing pneumonia were 
made by Rosenau and later by Meltzer, who atomized pneumococcus 
cultures into the trachea of dogs. 

Besides the diplococcus there are certainly other elements which 
contribute to the causation of the disease, else the frequent occurrence 
of the micro-organism in question in the saliva would make pneu- 
monia a much more common affection. The nature of the contributing 
causes is, however, obscure. Exposure to cold, general depression of the 
system, traumatism, alcoholism and other causes certainly predispose 
or help to determine the occurrence of the disease. These causes may act 
by temporarily increasing the virulence of the diplococcus or by lower- 
ing the resistive power. 



296 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — (See Diseases of the Lungs.) 

Pathological Physiology.— The diplococcus produces, in the first 
place, local lesions of the lungs; and in the second place, systemic infection 
and also general intoxication by toxins of uncertain character, which, 
though they give clinically the impression of exotoxins, are in all probability 
of intracellular origin. The infection-atrium is almost always the respira- 
tory tract. In the case of systemic infection the organism itself gains 
access to the blood and may produce secondary lesions in other organs. 
Infection with the diplococcus of pneumonia causes a pronounced reaction 
on the part of the blood in the form of leukocytosis, which may act in a 
way as a clinical guide to the course of the attack for a favorably pro- 
gressing case usually maintains a high white cell count. The pneumo- 
coccus seems to call forth a considerable fibrin formation since this 
substance is abundant in all infections with this bacterium and, as might 
be expected, when the body overcomes the infection, there is to be found 
an excess of ferments within the blood the purpose of which is to remove 
the precipitated protein and the cellular and bacterial debris. The end 
of pneumococcus disease in the lung is usually sudden and, being accom- 
pained by certain spectacular clinical symptoms, is spoken of as crisis. 
The cause of this has been ascribed to various factors, all of which prob- 
ably operate but no one of which will answer all points. During the 
attack opsonins and lysins increase so that at a certain stage they can 
remove more pneumococci than can be formed. Destruction of the 
exudate in the lung is accompained by an increase in acidity to a point at 
which the cocci cannot grow. These latter factors together with the 
increase of serum ferments mentioned above, determine the end of the 
pneumococcal power. After an attack the resistance remains high for a 
time but a true immunity does not appear in man, although by repeated 
injection of pneumococci into horses, highly immune serum has been 
produced by which passive immunity may be given. 

The pneumococci that cause the general disease, with the most striking 
lesions in the lungs known as lobar pneumonia, have been found to be 
divisible into several types according to serological grounds and the 
division is further supported by analysis of the epidemiological, clinical 
and pathological effects. For this country there seem to be four groups 
designated by Roman numerals I, II, III, and IV. The first three are 
called " fixed" types because they are fairly constant and uniform, 
while the last group is heterogeneous. (For the technique of their isola- 
tion and differentiation the reader is referred to text books on bacteriology. 
The first group seems to be most important, and against it a fairly useful 
antiserum for therapeutic purposes has been developed. Serum treat- 
ment has not been successful against the other three. Type III is the 
Pnc. mucosus a form probably indentical with the Str: mucosus already 
discussed. It is noteworthy that type IV, which supplies about one- 
fifth of all cases of penumonia, is frequently found in the throat of normal 
persons while the fixed types only occur in such a locality when a person 
has been in close proximity with a patient having a corresponding pneu- 
monia; the fixed types disappear from the throat shortly after an attack. 
It has not been found practicable to combine all these types and produce 



DISEASES DUE TO BACTERIA 



297 



one useful polyvalent antiserum. Vaccination with suspensions of killed 
cocci of the fixed types holds out promise of protection. 

The Diplococcus in Other Diseases. — -The Diplococcus pneumonias 
has been found in various conditions complicating pneumonia, and 
occasionally in lesions unassociated with croupous pneumonia. Among 
other lesions, meningitis, pleurisy, and other inflammations of the 
serous surfaces, abscesses, otitis media, and arthritis have been found 
to be due to this organism; or, at least, this organism alone has been 
found in some of these cases. Endocarditis is frequently caused by 
the pneumococcus. It may be primary or secondary. 

OTHER FORMS OF PNEUMONIA 

Among other varieties of pneumonia may be mentioned the catar- 
rhal or lobular form, the tuberculous form, and various irregular pneu- 
monias, partly cellular, 
partly fibrinous, partly 
purulent or hemorrhagic. 
Though the pneumococcus 
is more frequently present 
than any other single or- 
ganism in bronchopneu- 
monias after infectious 
diseases like measles and 
diphtheria and in various 
irregular types of broncho- 
pneumonia, different or- 
ganisms may be found in 
such cases, and some of 



4f \v 





Fig. 115. 

Fig. 115. — Bacterium pneumoniae of Friedlander. 



Fig. 116. 



Fig. 116. — Friedlander's pneumonia, showing the enormous number of bacteria in 
the exudate. 



these may be of etiologic importance in certain cases. Not rarely the 
pulmonary disease is the result of mixed (double or multiple) infection. 

Bacterium Pneumoniae of Friedlander. — This organism was re- 
garded at one time as the cause of croupous pneumonia. It prob- 
ably occurs in most cases as a mixed infection, though it may occa- 
sionally be the cause of catarrhal or irregular forms of pneumonia or of 
ordinary croupous pneumonia. With this organism also Meltzer has 
been able to produce pneumonia in dogs by atomized insufflation. 
The cases of pneumonia due primarily to the pneumobacillus are char- 
acterized by their virulence and a peculiar viscid character of the 
exudate in the lung. Friedlander's organism occurs as a distinct bacil- 



298 



A TEXT-BOOK OF PATHOLOGY 



lus, usually in pairs and surrounded by a capsule like that of the diplo- 
coccus (Fig. 115). Sometimes it may form chains of three, four, or 
more organisms. It stains well with the anilin dyes, but is decolorized 
by Gram's method. A characteristic culture is obtained in gelatin. 
The puncture-culture is characterized by a luxuriant growth at the 
top and a considerable vegetation all along the track. This leads to a 
nail-shaped growth. The gelatin does not liquefy. Upon agar a con- 
siderable whitish or yellowish moist growth occurs upon the surface. 
There is formation of gas in media containing glucose, and often also 
on potato. 

A number of organisms closely related to Friedlander's pneumo- 
bacillus have been classified under the generic name Bacterium muco- 
sum capsulatum. Among these are the B. lactis aerogenes, B. acidi 
lactici, B. ozcence, and B. rhino scleromatis. The several types differ some- 
what in their power to ferment various carbohydrates. 

Other Organisms in Pneumonia. — Among the various organisms 
that have been found in bronchopneumonia or less commonly fibrinous 
pneumonia are the Streptococcus pyogenes, more rarely the influenza 
bacillus, the Bacillus coli communis, the typhoid bacillus, the bacillus 
of glanders, of the plague, and occasionally other organisms. In some 
of these cases the disease may be the result of double infection. 

Tubercle Bacillus. — A uniform pneumonic process may be due to 
simple infection with the tubercle bacillus, or to mixed infections. 

Micrococcus tetragenus. — This form is a Gram-positive micrococcus 
from 1 to 2 ju in diameter, and receives its name from the peculiar asso- 
ciation in groups of four. It occurs in the sputum and contents of 
cavities in pulmonary phthisis, and occasionally elsewhere. It may 
give rise to general sepsis. 

Micrococcus catarrhalis is a micro-organism found by Pfeiffer in 
cases of bronchitis in which there was a great deal of expectoration, and 
in which the symptoms resembled those of influenza. It is a small 
coccus, usually occurring in diplococcic form, and resembling the micro- 
coccus of gonorrhea. It often is seen within the pus-cells, and occurs in 
large numbers in the sputum and nasal secretion of individuals suffering 
from bronchitis. It does not cause the constitutional disturbance that 
is caused by the bacillus of influenza, but is often found as an associated 
infective agent in cases of pneumonia due either to the Diplococcus 
pneumoniae or to the bacillus of influenza. To obtain it in pure culture 
it is best grown on blood-agar. It grows as sharply defined, somewhat 
raised, granular, yellowish, non-transparent colonies on the surface of 
agar. It resembles the Staphylococcus pyogenes aureus, but the colonies 
are much more raised and harder. They can be picked up on the end of 
the needle, and are crushed with difficulty. The needle can be drawn 
across the culture without destroying the integrity of the individual 
colonies. After the first generation the micrococcus grows well on 
ordinary agar, but it must be transferred every three or four days to 
be kept alive. It is decolorized by Gram's method. The exact path- 
ogenic power of this coccus is not yet fully known but it probably is 
more important than customarily believed, in that it acts as an assistant 
to the well recognized pathogenes of the respiratory tract. It seems to 



DISEASES DUE TO BACTERIA 



299 



be of importance in the pneumococcal or streptococcal anginse, since, 
according to the work of one of the authors, a culture of one of these cocci 
is much increased in pathogenicity for guinea-pigs when mixed with 
Micrococcus catarrhalis. 

DISEASES Due to Bacillary FORMS 
DIPHTHERIA 

Definition. — Diphtheria is an infectious and contagious disease 
caused by a specific bacillus. 

Etiology. — The Bacterium diphtheria was discovered by Klebs, but 
more accurately studied by Loffler, and is, therefore, called the Klebs- 
Loffler bacillus. This organism is a rod varying in length from 1 to 6 m 




Fig. 117. — Diphtheria bacilli from an eighteen-hour blood-serum culture. 

rather thick, and with somewhat swollen ends. It is readily demon- 
strated in the local lesions of the mucous membranes or skin, where it 
may be quite abundant; the individual bacilli, however, are separate 
from one another. The organism is peculiar in its great irregularity 
of shape and size, particularly in cultures (Fig. 117). Seemingly 
branched forms have been observed, and some investigators have viewed 
the organism as a streptothrix or even as one of the hyphomycetes. Fre- 
quently one end is especially large, giving a club-shaped appearance; 
some of the bacilli are very large; some present rounded granules at 
either end, the so-called polar granules or Ernst bodies. The bacillus 
is readily stained with aqueous solutions of basic stains, especially with 
those rendered slightly alkaline. (Loffler 's solution — 'Saturated aqueous 
solution of methylene-blue, 30 c.c, in aqueous solution of potassium 



300 



A TEXT-BOOK OF PATHOLOGY 



hydrate, 1:10,000, 100 c.c. — is the favorite stain.) The color is retained 
when stained by Gram's method. The stained specimen shows the mor- 
phology of the bacillus very clearly. The rounded ends generally stain 
more deeply than the shaft of the bacillus, so that the appearance some- 
what suggests a diplococcus, or as a row of cocci. Not rarely transverse 
fractures give the organism the appearance of disjointed segments. 
There are no flagella, and the bacillus is not motile. Spores have not 
been demonstrated. 

Cultivation. — The most characteristic cultures are obtained upon 
blood-serum, especially such as contain a small amount of glucose. Upon 
this medium there is formed within six, twelve, or twenty-four hours a 
thin, whitish or yellowish-white layer of irregular outline, often showing 
separate smaller colonies around the edge. Other organisms found in 
the throat are slower in growth, and do not, therefore, interfere with the 
diagnosis. 

Pathogenicity. — When cultures in bouillon are injected beneath 
the skin of a guinea-pig a fibrinous inflammation with more or less 
widespread edema results, and the animal dies in from twenty-four to 
ninety-six hours. Congestion of the adrenal, necrotic foci in the liver 
and other organs are found postmortem; the neighboring lymphatic 
glands are enlarged. If the animal survive, paralysis may make its 
appearance, as in human beings recovering from the disease. The 
pathogenicity has also been shown by inoculation of various other 
animals, and definitely by accidental infection of man. 

Klebs-Loffler bacilli may be found in the pharynx of a person show- 
ing no indication of disease. This indicates that the organism has not 
found a favorable soil for its development or no abrasion or opening 
into tissues that will support its growth. The bacillus may, 'however, 
thrive and multiply for a considerable time upon the mucous membrane 
of such a throat, as it may upon food, clothing, or other infected 
materials. 

Mixed Infection in Diphtheria. — Other organisms, notably strep- 
tococci, staphylococci, and pneumococci, may be associated with the 
diphtheria bacillus, and may be actively concerned in the local or general 
pathological processes. The streptococcus is especially potent as an 
associated cause. The streptococcic infection may precede or follow the 
diphtheritic infection. Various organisms of a saprophytic nature may 
cause putrefactive changes in the pseudomembrane. 

Predisposing Causes. — Some predisposition is necessary for the 
development of the disease. In part, accidental conditions, such as 
pharyngitis, laryngitis, abrasions, etc., furnish a favorable opportunity 
for the infection. On the other hand personal susceptibility seems to 
play a very definite role in the causation of the disease for it has been 
found that a large percentage of children are liable to the infection and 
that this susceptibility decreases as age advances. The means of eliciting 
a knowledge of the receptivity of a given person lies in the Schick test 
whereby a fiftieth minimun lethal dose of toxin is injected into the skin 
of the person to be tested. If the individual be immune, no reaction 
follows whereas if he be susceptible, a red swollen area arises at the point 
of "injection. It has been found that where no reaction occurs, each 



DISEASES DUE TO BACTERIA 



301 



cubic centimeter of the persons blood contains one thirtieth of a unit 
of antitoxin, a quantity apparently adequate to protect him. 

The diphtheria of birds, calves, and certain other animals is distinct 
from the human disease; and the organisms are in no way related. 
Human diphtheria may occur in cats, and these animals may propagate 
epidemics. 

Pseudomembranous (fibrinous) inflammation is not invariably caused 
by the diphtheria bacillus (see Inflammation). Among the organisms 
capable of causing somewhat similar pseudomembranes, the most fre- 
quent is the Streptococcus pyogenes; another important one is the 
pneumococcus. 

Distribution of the Bacilli. — The organisms are abundant in the 
pseudomembranes of diphtheria, but are only exceptionally found 
in the blood or internal organs. The visceral or nerve lesions are due 
to the toxins, and not to the bacillus. The same is true of experimental 
diphtheria. The internal lesions may be produced by injection of the 
toxin obtained by filtering a bouillon-culture through a Pasteur filter. 

Pathological Anatomy. — Diphtheria is primarily a local disease of 
the surface membranes and while the upper respiratory and alimentary 
tracts are the commonest seats any area is liable especially when damaged 
(wound diphtheria). The bacillus lodges in the mucous membrane 
or skin, and produces a pseudomembrane. This consists of fibrinous 
exudation in the form of fine granular material or a fibrillar network, 
in which are embedded the epithelial cells and other tissue elements 
and infiltrating leukocytes. The epithelial cells rapidly undergo coagu- 
lation necrosis or granular degeneration, as do also the connective 
tissues when the process extends beneath the mucosa. The blood-vessels 
become obstructed by thrombosis or compression, and the tissue is, 
therefore, avascular. Nearly always the pseudomembrane thus formed 
is attached to the underlying tissues, and when removed a raw and 
bleeding surface is exposed. The depth of involvement, however, 
varies; sometimes the submucosa is soon involved; more often the 
disease is practically confined to the mucosa. 

The macroscopical appearance is that of a whitish, dirty-yellowish, 
or brownish membrane upon the mucous lining of the throat. This 
begins as one or several patches upon the tonsil, and spreads rapidly to 
the neighboring parts. In other situations the appearance is much the 
same. Inflammatory swelling beneath and around the diseased area is 
habitual. It is of great clinical importance to recognize that true diph- 
theria may occur in the form of typical follicular tonsillitis. 

Internal or visceral lesions may occur in the course of diphtheria or 
during convalescence. They are due to the action of the toxin, and not 
of the bacillus. Necrotic foci in the liver, showing advanced cellular 
degeneration of the cells with hyperchromatosis of the nuclei, and 
similar lesions of other organs, may be seen in the human body, as in 
animals killed with the organism or its toxin. Swelling of lymph-tissue 
is common, the principal point of attack being endothelium. This 
may go on to focal necrosis. Myocarditis and myocardial degenera- 
tion, renal degeneration and nephritis, and, most interesting of all, 
karyolytic and^fatty degeneration of the peripheral nerves and neuritis 



302 



A TEXT-BOOK OF PATHOLOGY 



may be met with. All of these will be described elsewhere. This is 
believed to be due to the toxone fraction of the toxin. 

Pathological Physiology. — As has been said, the disease is pri- 
marily local, and the bacilli nearly always remain localized in the 
superficial lesions. They have been found in the internal organs, 
showing that they can enter the blood-stream. The local effects 
are believed by some to be due to an endocellular toxin. The 
general manifestations — fever, prostration, and the visceral lesions — 
are caused by poisonous substances elaborated by the growth of the 
bacilli. There are probably several substances of this sort, but one in 
particular — the toxin — is most important. This may be obtained by 
filtering bouillon-cultures through porcelain, and by its injection the 
constitutional and some of the local manifestations of the disease may 
be induced in animals. Successive introduction of increasing doses of 
toxin causes the development of antitoxin substances that may finally 
accumulate in the blood to such extent that the animal becomes immune 
to the most virulent bacilli. The antitoxic substance or substances, or 
antitoxin, found in the blood and the blood-serum of immunized animals 
will render other animals immune for a time, or combat and overcome 
the disease if already existing. Simultaneous injection of antitoxin and 
of many times the ordinarily fatal dose of toxin or diphtheria-cultures 
leaves an animal unharmed. The value of the antitoxin in animal 
experimentation is beyond doubt. In the human being there is scarcely 
any doubt of its potency, though, of course, crucial experiments cannot 
be made. Experience has shown that its therapeutic use in diphtheria 
should never be omitted. 

After an attack of diphtheria there is temporary immunity, but this 
passes off and successive attacks may thus occur in the same person. 

Diphtheria=like bacilli are sometimes found in the pharynx of 
healthy individuals in some cases, as well as upon the hands, hair, or in 
other parts of the body. The yare also found in various forms of rhinitis, 
conjunctivitis, and non-diphtheric angina. These may differ from the 
virulent bacilli in being somewhat shorter and in growing more lux- 
uriantly. Their distinctive character, however, is their relative harm- 
lessness when injected into animals. 

Pathogenic powers have been ascribed to certain members of the 
pseudodiphtheria group of bacteria. Some seem to be able to pro- 
duce a transmissible angina that is not favorably influenced by diph- 
theria antitoxin. Others of the group may cause general infection or 
severe local disturbance. 

The exact relationship of the members of the diphtheria group is 
not yet decided, but the classification of Emerson is quite good : 

"(1) Bacilli with typical morphology, typical cultural characteris- 
tics, especially the ability to form acid from glucose, and which produce 
the typical lesions in animals, are, in the opinion of all observers, Bacillus 
diphtheria?. 

"(2) Bacilli with typical morphology and typical cultural reactions 
especially the ability to form acid from glucose, but which are 
not pathogenic to animals, may be called avirulent diphtheria bacilli. 

"(3) Bacilli with typical morphology, but which do not conform in 



DISEASES DUE TO BACTERIA 303 

their cultural reaction with the diphtheria bacillus, and which are not 
pathogenic for animals or do not produce typical lesions, may properly 
be called pseudodiphtheria bacilli. 

"(4) Finally, there are a number of organisms which resemble 
Bacillus diphtherise in many ways, but whose morphology is not ex- 
actly the same, . . . and which have different cultural characteristics, 
and differ in their pathogenicity. This group certainly includes the 
pseudodiphtheria bacillus of Hoffman, the xerosis bacillus, and others." 

The pathogenic members belong in the first and third or possibly the 
first three groups. A difference of the pseudo- and true diphtheria 
bacilli not mentioned above is that the former do not produce a 
soluble toxin, but upon injection excite a bactericidal serum in experi- 
mental animals specific for each variety. The so-called virulent pseudo- 
diphtheria bacilli have been found in cystitis, septicemia, and other 
conditions. They are very common in mixed infections, and have 
been said to be more potent in continuing an infection than in inciting it. 

TYPHOID FEVER 

Definition. — Typhoid fever is an infectious disease, with char- 
acteristic lesions of the intestines, and due to a specific bacillus. It is 
important to recall the fact that local or general typhoid septicemia may 
occur without the intestinal lesions or usual clinical features of typhoid 
fever. In such cases local inflammatory lesions, suppurations, necroses, 
or septicemia have been observed. 

Etiology. — Certain predisposing features make individuals more 
liable at one time than another to this disease. It occurs in adoles- 
cence and the young, but rarely in the old. Typhoid fever is especially 
a disease of the temperate zones, and is most abundant in the autumn. 
While miasmatic conditions are now known to have nothing to do with 
the cause of the disease, prolonged bad weather especially with exposure 
of a susceptible person, favors its development ; in a like manner excessive 
fatigue, insanitary dwellings or poor personal hygiene decrease resistance. 
One attack usually confers immunity for the rest of life; exceptions, 
however, are met with. 

The Bacillus. — The Bacillus typhi abdominalis, the specific organism, 
was discovered by Eberth and isolated by Gaffky. It is a short bacillus, 
from 1 to 4 m in length and 0.5 to 0.8 ju in thickness. The ends are 
rounded and often somewhat plump. In culture these rods or bacilli 
occasionally form long chains, but in the tissues they are never so ar- 
ranged. The organism is actively motile, this being due to flagella, 
of which there are eighteen or twenty attached to the periphery (Fig. 118) . 
When stained with alkaline methylene-blue or other stains there are some- 
times dark-colored spots at the ends of the organism. These were formerly 
regarded as spores, but are now recognized as areas of protoplasmic 
condensation. Under certain circumstances the condensation is seen 
in the center and vacuole-like formations are found at the ends. The 
organism is readily stained, but decolorizes very easily, and is, therefore, 
difficult to demonstrate in tissue. The bacilli are, as a rule, found in 
clusters. These groups may, however, be few in number, and thus 



304 



A TEXT-BOOK OF PATHOLOGY 



difficult to detect in the organs where they should be sought in the 
areas of large phagocytic cells. 

Cultivation. — Artificial cultures of the bacillus have been obtained 
from the spleen and other organs, as well as directly from the blood, 
stools, and urine of patients suffering from the disease. They grow 
very well upon the ordinary culture-media, such as agar-agar, gelatin, 
and potato, the temperature of the body being most favorable, but some 
growth occurs at the ordinary temperature of the room. Upon gelatin 
and agar there are formed irregularly whitish films, which on close 
inspection with the lens show a granular appearance. This growth, 




Fig. 118.- — Bacillus typhi abdominalis, from an agar-agar culture six hours old, showing the 
flagella stained by Loffler's method; X1000 (Frankel and Pfeiffer). 

however, is not distinctive. Upon acid potato a characteristic transpar- 
ent pellicle is formed. This may be invisible except to the trained eye, 
but on scraping the surface with a platinum wire the pellicle can be 
raised, and on microscopical examination it is found to be composed of 
bacilli. When cultivated in milk there is slight acidity, but coagulation 
does not occur. When grown in agar containing a little glucose no 
fermentative gas results. Another feature of importance is the absence 
of indol reaction, the addition of potassium nitrite and sulphuric acid 
to bouillon-cultures causing no rose color, such as occurs with some 
other organisms. 

The biological characters of the typhoid bacillus are distinct enough 
when isolated, but as it occurs so frequently in company with the colon 
bacillus, whose colonies are similar, numerous technics have been devised 
for its isolation. These must be studied in books on bacteriology. (Com- 
pare Cultivation of Typhoid and Colon Bacilli, pages 304 and 310.) 
One of the most reliable tests for the identification of the typhoid bacillus 
is the Widal reaction, the clumping of the organism by the blood of 
typhoid patients, or, better, by the serum of animals immunized, against 
a known culture of the Bacillus typhosus. Human typhoid serum may 
clump colon bacilli also in low dilutions, j 



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305 



Pathogenicity. — Animal experimentation has thus far been unsat- 
isfactory. A few observers have succeeded in producing illness and 
intestinal lesions by feeding animals with typhoid cultures, particularly 
after the stomach and intestines have been rendered alkaline with 
soda and peristalsis has been checked with opium. In most cases in- 
jection of the typhoid bacillus has produced septicemic manifestations. 
The anthropoid apes have been infected by feeding and injection with 
typhoid bacilli, the resulting intestinal and other lesions bearing a rather 
distinct similarity to those in man's natural disease. The constant 
occurrence of the germ, its absence from other conditions, and the 
absence of any other germ as a constant accompaniment of typhoid 
fever, have led to the general acceptation of this as the specific cause. 
Moreover, its properties are such that the spread of the disease in the 
acknowledged ways is entirely compatible with the acceptance of the 
bacillus as the specific cause. 

Distribution. — The typhoid bacillus occurs both within and without 
the human body, and doubtless multiplies greatly in the external 
world when the conditions are favorable. It is found with great regu- 
larity in the blood of typhoid patients, especially in the first week of 
the disease, therefore, it is easily understood how it appears in all the lesions 
peculiar to the infection, even to the rose spots in the skin. It occurs 
in the lesions of the intestines and in the intestinal contents, especially 
during the second and third weeks of the disease. It is usually less 
abundant, but often present in the spleen, liver, and kidneys; it may 
occur in considerable abundance in these organs when there are local 
complications. It is almost always present in the gall-bladder in cases 
of typhoid fever, and frequently occasions cholecystitis and not rarely 
initiates the formation of gall-stones. It also occurs in the lungs, in 
the parotid gland, and in other organs, and posttyphoidal abscesses 
may contain the organism in abundance. Complicating lesions of other 
organs may be dependent solely upon the specific bacillus, it being 
capable even of acting as a pyogenic organism, or they may be dependent 
upon secondary or mixed infections. Microscopically it is to be found 
only in the intestinal wall at the site of ulcers and in the collections of 
macrophages to be described below. 

The typhoid bacillus is peculiarly resistant, and may thrive upon 
clothing, in soil, and in water for a long time. Cold has no effect, the 
germ being virulent after freezing and thawing. It has rather more 
resistance to carbolic acid than other members of the typhocolon group. 
These features help to explain the spread of the disease and its general 
prevalence. The organisms are discharged from the body of a patient 
suffering from the disease mainly in the stools, but in part also in the 
urine, sweat, and other excreta. If they are not at once destroyed, 
contamination of clothing, soil, water, and etc., may occur, and subse- 
quent infection of susceptible individuals takes place through drinking- 
water or food with which the infected water or other matters have come in 
contact. The excretion of the germs in so many ways gives oppor- 
tunity to attendants to soil the hands and clothing, a mode of trans- 
mission, the socalled "direct," that grows in importance as more facts are 
observed. Indeed some writers would contend that this is the principal 
20 



306 



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method of spread, but in summer and fall one must reckon with flies 
which can easily soil themselves in the sick room and it is known that 
bacilli may pass through their alimentary tract. It is possible that in- 
fection may occasionally take place through the lungs by inhalation of 
dust. This must be very rare. Intra-uterine infection undoubtedly 
occurs in some instances in which the mother is suffering from typhoid 
fever. 

One means of transmission of typhoid is by means of "carriers." 
Carriers are persons who after recovery from a typhoid infection harbor 
somewhere within themselves virulent bacilli without active evidence 
thereof. They are usually in the gall-bladder, but may be in lymph- 
nodes or liver. They may be excreted and pollute water or surrounding 
objects. The reason for this carrying of germs may lie in the fact that 
their focus is protected from the antibodies of the blood, or they may be 
"fast" strains. 

Pathological Anatomy. — The lesions of typhoid fever are con- 
sidered with the diseases of the intestines. It is important, however, 
to add in this place that widespread changes may occur in this disease 
as a result of the action of the bacillus. Thus there may be focal necroses 
in the spleen and liver, degenerative changes in the kidneys and muscles, 
and inflammatory changes in various glandular organs, the periosteum, 
the bones, or the connective tissues, the result of the direct action of 
the bacillus. There is a reaction on the part of lymphadenoid tissue 
everywhere throughout the body, including all organs, even the larynx, 
in which definite lymphoid swellings occur in the mucosa, at times 
leading to ulceration. The minute anatomy of typhoid fever is in a 
sense peculiar to the disease and the microscopical picture depends 
upon the same kind of changes in different localities. The bacillus 
exerts a toxic effect which produces the changes known as Zenker's 
hyalin and also some non-specific focal necroses, but characteristic 
action lies in. the stimulation of large mononuclear phagocytes. These 
latter are believed by some to be purely endothelial in origin, by others 
as derivatives of tissue cells. There is indeed a very evident stimulation 
of endothelia for these cells swell within capillaries and small arterioles, 
even it is claimed, to their occlusion, and probably this causes small 
necroses in which the large cells are numerous and outlast the parenchyma, 
removing the remnants of the latter by their phagocytic power. Whether 
or not this be the origin, there are within lymphatic organs (typhoid 
spleen) and in the interstices of parenchymatous viscera, definite accumu- 
lations of large pale endothelioid cells, and there is apt to be tissue 
detritus about them. These cells play also a very large part in the infil- 
tration in Peyer's patches. While the necroses within organs may be as 
massive as that occurring in the intestinal lymphatic tissue, they are 
usually so tiny that discovery is made first by the microscope. The 
typhoid bacillus further exerts effect upon mononuclears by causing 
lymphatic follicular hyperplasia, in nodes, viscera and in the marrow, in 
the last position, myelocytic cells seeming to be repressed in production; 
this is all reflected in the blood count where one finds a leucopenia with 
relative lymphocytosis. 



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307 



Pathological Physiology. — The typhoid bacillus elaborates toxic 
substances which give rise to fever and other general symptoms as 
well as to local lesions. Brieger and Frankel claim to have separated a 
specific toxalbumin. Whether this be the poison or not, there is no 
doubt that some form of a toxic body is present, and is endotoxic, not 
extracellular. During the existence of the disease the system reacts, 
in some way as yet unknown, to check its progress and to bring it to a 
termination at the end of four weeks, and lasting immunity is usually 
conferred. Whether or not there are distinct antitoxic substances 
remains to be determined. 

Protective vaccination with killed typhoid bacilli has been practiced. 
The results of the English and American armies are most encourag- 
ing. Both the morbidity and mortality have been reduced. Russell, 
of the United States Army, concludes that it is a harmless efficient 
protection against infection and carriers, seldom giving any dis- 
comfort, and resulting in an immunity that probably lasts over two 
years. 

Vaccination treatment has been tried during an attack, but with 
indifferent results. No efficient antiserum has been found. 

Agglutination; Gruber-Durham Phenomenon; Widal Reaction. 

This reaction is due to the presence, in the serum of inoculated animals 
or in that of man, of a substance capable of causing massing together 
and loss of motility of the specific micro-organisms concerned in the 
infection from which the animal or man furnishing the serum is suffering. 
This phenomenon may be studied macroscopically or microscopically. 
Macroscopically, we speak of a positive reaction when a distinct sedi- 
ment is seen in the glass containing the culture in a liquid medium, while 
the rest of the fluid remains clear, whereas before the phenomenon has 
taken place the whole fluid has had a diffuse cloudiness. Microscopically, 
we speak of a positive reaction when there occur a clumping and loss of 
motility of the bacteria, and, at the same time, the control remains 
free from all massing together. A certain amount of spontaneous 
clumping often occurs in the controls, but the organisms in the clump 
still exhibit motility, or there are actively motile individuals at the 
periphery or a little separated from it. 

In studying agglutination with special reference to the Widal reaction, 
the best results are obtained when one always uses a definite quantity of 
the culture with a definite quantity of the serum. Cultures grown at 
temperatures of 25° to 35° C. (77°-95° F.) are better adapted to the reac- 
tion than those grown at 37° C. (98.6° F.). The more virulent the cul- 
ture, the less readily is agglutination obtained. In reference to typhoid 
bacilli, it is true that a twenty-four-hour culture is the best, since in 
older cultures pseudo-agglutination shows itself more readily. Widal and 
Foerster found no difference in the agglutinating properties of typhoid 
bacilli which had been formalized five months previously from the 
agglutination seen in fresh cultures. The time that it takes for agglu- 
tination to occur is dependent upon the activity of the serum and 
upon the temperature. At what day after the last inj ection in the immuni- 
zation of an animal the agglutination will appear, or at what day after 
the beginning of the disease in man agglutinin will first show itself, 



308 



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cannot be determined definitely. In men who are ill with typhoid 
fever the reaction has been demonstrated as early as the third day 
after the first appearance of the disease, but is often delayed much 
longer. Agglutinin remains in the blood for varying periods. In chil- 
dren recovering from typhoid fever the average time has been about 
two months after the convalescence; in adults the average length of time 
is half a year. In the differentiation between the typhoid and colon 
bacilli by agglutination a very active serum is necessary. By im- 
munizing an animal with typhoid bacilli we can obtain a serum which 
will agglutinate both the typhoid bacilli and the colon bacilli, but this 
occurs in different dilutions. With the typhoid bacilli the dilution 
may be as high as 1 : 40,000 or 1 : 100,000, while with the coli the highest 
effective dilution will probably be 1 : 2000. The explanation of this is 
that there are group agglutinins which have a certain effect on any one 
of a group of allied but not identical organisms, and possibly even the 
specific agglutinins have a certain limited effect (shown when the dilu- 
tion is not high) on other organisms than those for which they are specific. 

In the clinical use of the test the dilution of the serum should be not 
less than 1 : 50. An active serum will respond very quickly with dilu- 
tions of 1 : 100 or more. 

This reaction was found in 2283 cases of typhoid fever reported 
by various writers, and was absent in 109 cases of typhoid fever. It 
was absent in 1365 non-typhoid cases, and present in 22 non-typhoid 
patients. It was, therefore,- found in 95.5 per cent, of the typhoid cases, 
and was absent in 98.4 per cent, of the non-typhoid cases; or, taking the 
entire 3779 cases, the correct result for diagnosis was arrived at in 96.5 
per cent. The reaction sometimes persists for some years after the 
attack of typhoid fever. It was the principal specific diagnostic test for 
typhoid fever before blood culture was perfected but has now been 
largely supplanted by the latter whenever adequate laboratory facilities 
permit. Three-fourths of all cases will give positive results if the culture 
he made in the first two weeks of the attack. 

Paracolon Infection; Paratyphoid Infection. — This is an acute infec- 
tion appearing sporadically and in epidemics resembling typhoid fever 
clinically, but in which the Widal reaction is persistently absent, and 
in which bacilli closely resembling the typhoid or colon bacilli, though 
differing in some essential particulars, are isolated from the blood and 
tissues. The intermediate organisms here referred to differ from the 
bacillus of typhoid by their ability to produce gas in glucose-containing 
media, and to produce an alkaline reaction in some media. They differ 
from the Bacillus coli communis by not coagulating milk, not fermenting 
lactose, and by failing to form indol. The group of intermediates has 
been divided into a paracolon and a paratyphoid group, according to 
the closer resemblance to the colon group on the one hand or the typhoid 
bacillus on the other. The paratyphoids have been divided by Schott- 
muller into "A" and "B" groups, depending upon the acid reaction in 
milk. The "A" strains are biologically nearer the bacillus of Eberth, 
while the "B" organisms are nearer the paracolons. Infections with 
the "B" paratyphoid bacillus outnumber those with "A." Members 
of the paracolon group are less closely related — as, for example, in 



DISEASES DUE TO BACTERIA 



309 



the matter of interagglutination — than those of the paratyphoid 
group. 

The paratyphoids give rise to a milder form of infection than typhoid 
fever, but the condition is transmissible in the same manner. The 
diagnosis is to be made by differential agglutinin tests when the bacillus 
cannot be isolated from the case. 

The paracolons are closely allied to the Bacillus psittacosis of Nocard 
the B. icteroides of Sanarelli, the bacillus of hog-cholera, the B. enteritidis 
of Gartner 1 (meat-poisoning bacillus), and the B. dysenterice of Shiga. 
Infections with this group are more like toxemias, being rapid in onset, 
stormy in course and short in duration. 

Pathological Anatomy. — The gross changes are not uniform but in 
the slowly progressive cases, resembling typhoid in course, the lesions 
are similar to those in that disease. The most constant change is 
splenic enlargement, which is the same as that of septicemia. The en- 
dothelial cells are loaded with pigment evidently the result of hemolysis, 
but these macrophages are by no means as prominent as in typhoid. 

Intestinal Lesions. — In a few cases, ulcerations resembling those of 
dysentery rather than those of typhoid fever are discovered. Peyer's 
patches and the solitary follicles are usually unaffected, as are also the 
mesenteric glands. In the rapid toxemic cases, a congestion may be the 
only thing visible but a severe hemorrhagic or even pseudomembranous 
enteritis has been reported. 

In the cases of Longcope and Wells and Scott focal necroses in the 
liver, differing from those of typhoid in not containing endothelial cells, 
were fbund. The changes of proliferation and phagocytosis described 
by Mallory for typhoid fever are almost entirely absent in the intes- 
tinal lesions and very slight in the mesenteric glands, not being more 
conspicuous than that seen in simple enteritis. 

The anatomical picture is that of a septicemia with splenic enlarge- 
ment and occasionally non-specific ulceration in the intestines. The 
escape of Peyer's patches suggests an essential if obscure biological dif- 
ference between the typhoid and paratyphoid organisms. 

Nature of Paratyphoid Infection. — The tendency of most pathol- 
ogists at the present time is to regard paratyphoid infection as distinct 
in a bacteriological sense rather than in a clinical or general pathological 
sense, in the same way as pneumonias of varying bacteriology are dis- 
tinguished only etiologically. The paracolon infections are almost 
universally regarded as the result of meat poisoning; they are unusual 
in this country. Among lower animals, especially the carnivors, disease 
the result of paracolon and enteriditis infection is quite common as 
enteritis, choledochitis and septicemia. 

BACILLUS COLI COMMUNIS 

Synonyms. — Bacterium coli commune. It is customary to speak 
of the " colon group/' since it has been recognized that several and per- 
haps many forms, varying in their ferment action only, have been 
classed under the name Bacillus coli communis. A number of organ- 

1 See Ptomain Poisoning, page 38. 



310 



A TEXT-BOOK OF PATHOLOGY 



isms described under different names are probably identical. Among 
these are Bacillus neapolitanus of Emmerich, B. pyogenes fceiidus of 
Passet. Several other organisms are either closely allied or identical. 

Morphology. — 'The Bacillus coli communis is an organism almost 
exactly like the typhoid bacillus in appearance. It is rod shaped, but 
sometimes elongated and filamentous; at other times (young forms) 
short and rather rounded — coccus-like. It is motile, and has flagella 
attached to the periphery of the bacillus. The flagella are shorter, more 
slender, and less numerous than those of Eberth's bacillus (three to 
ten in number), and the motility of the organism is less uniform and 
active. It may be stained by ordinary solutions of anilin dyes, particu- 
larly with alkaline or carbolized solutions. It is decolorized by Gram's 
staining method. The stained bacillus shows light-colored or unstained 
portions like those of the typhoid bacillus. True spores have not been 
detected. 

Cultivation. — The organism grows luxuriantly upon ordinary 
media. When cultivated in gelatin or agar containing glucose, active 
gas production results. In liquid media (bouillon) a peculiar odor is 
developed. Addition of nitrites and pure hydrochloric or sulphuric acid 
causes a rose-red color — indol reaction. Milk is readily coagulated, 
partly as a result of acid formation and partly by the elaboration of a 
coagulating ferment. 

Distribution and Pathogenicity. — The colon bacillus is a normal 
inhabitant of the gastro-intestinal tract. It seems to exercise a bene- 
ficial effect in restraining (by its own active growth and acid formation) 
the growth of putrefactive and possibly pathogenic organisms. In 
certain inflammatory diseases of the intestines, however, it seems to 
increase in numbers and doubtless also in virulence. The organism may 
be found outside the body in various situations, particularly in water. 

The Bacillus coli is capable of producing inflammatory conditions 
in different situations. Injected into the peritoneal cavity of animals it 
gives rise to acute fibrinopurulent peritonitis, and in other parts of the 
body has analogous effects. 

It has been found in various disease of the gastro-intestinal tract, of 
the biliary passages, of the urinary system, and of other parts, and is 
doubtless the direct cause of some of these, as the conditions present 
are practically the same as those produced by experimental inoculation 
of pure cultures. 

The lesions in the liver may be necrotic, or interstitial or catarrhal in- 
flammation. Colon bacilli are said to precipitate bile-salts. Whether 
by this means or by inflammatory products, they probably have a 
part in the production of gall-stones. 

Among the gastro-intestinal troubles it has been found in suspicious 
abundance in various forms of enteritis, in the distended and suppurating 
appendix, and even in Asiatic cholera. It is known that the strangu- 
lation of a knuckle of intestine by a ligature leads to rapid increase of 
virulence of the contained bacilli. It is possible that in appendicitis 
and in other intestinal diseases similar conditions lead to increased 
infectivity, and thus cause an ordinarily harmless organism to become 
virulent. In the cases of Asiatic cholera in which this organism has been 



DISEASES DUE TO BACTERIA 



311 



found the specific germ of cholera has probably been overlooked or has 
disappeared during the rapid multiplication of the saprophytic Bacillus 
coli. 

Peritonitis may result from escape of the. bacillus through a rup- 
tured intestine or directly through the wall of the bowel. The latter 
is particularly prone to occur in cases of strangulation of the intestines. 

Various inflammatory diseases of the urinary tract, such as cystitis, 
pyelitis, and pyelonephritis, are occasioned by this same germ, which 
first reaches the bladder through the urethra or by penetration of the 
wall of the bowel and then of the bladder, or, in other cases, infects the 
kidney primarily, having been carried there by the blood. 

Finally, there are cases of peritonitis secondary to enteritis, pleurisy, 
endocarditis, and other inflammatory diseases, apparently caused by 
this organism. 

Pathological Physiology. — Little is known of the toxic effects of 
colon bacillus infection. Some toxic substance is doubtless produced, 
which, according to Vaughan, is a highly thermostabile intracellular 
substance. A reaction similar to the Widal reaction obtained with the 
typhoid germ has been found to occur when cultures of the colon bacillus 
are subjected to the action of serum from an animal inoculated with 
this organism or from a person suffering with appendicitis or other dis- 
eases, either due to colon infection or accompained by such. 

There is no antiserum for colon infections, but vaccination treat- 
ment has been used with success. 

THE DYSENTERY BACILLUS 

Certain types of dysentery in the tropics and of acute dysentery 
of temperate climates are accompained by bacilli, first recognized by 
Shiga, and afterward studied by Flexner, Park, Kruse, and others. 

The organisms resemble those of the typhoid group, except that 
they are questionably motile bacilli with few, if any, flagella. 

In gelatin culture the colonies resemble those of typhoid bacilli. 
In bouillon a diffuse cloudiness without production of indol is observed. 
In glucose bouillon the bacillus does not produce gas. The organisms, as 
observed by different observers, have differed in some particulars. The 
original form recognized by Shiga does not ferment mannite, maltose, or 
saccharose. Some of the later types have been found to ferment mannite 
and to produce indol, while still others actively ferment mannite and also 
maltose and saccharose. 

The bacillus produces a highly toxic pioson, probably of both intra- 
and extracellular nature. It is resistant up to 70° C. (158° F.), and to 
proteolytic ferments, and the circulation of this poison is responsible 
for the clinical symptoms and simple general pathology since the bacilli 
remain in the intestinal wall and lymp nodes. A predilection for the colon 
seeems to exist for when animals are injected with bacilli or their dead 
bodies, lesions are formed there first. During an attack specific 
agglutinins are formed and these can be used to distinguish the type of 
infecting organism. 

The Shiga type is responsible for most cases of tropical bacillary 
dysentery, and indeed is found in temperate zones but the other types 



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A TEXT-BOOK OF PATHOLOGY 



mentioned are more common in the latter regions. The disease is dis- 
tributed probably by polluted water chiefly but bad personal hygiene is 
often responsible. It appears in all kinds of public institutions or takes 
the form of sporadic or epidemic summer diarrhea in children. A fairly 
useful antitoxic and antibacterial serum has been prepared for thera- 
peutic use against Shiga infections but it is powerless against the other 
forms. 

The pathological anatomy and physiology of dysentery will be con- 
sidered in the section on Diseases of the Intestines. 

INFLUENZA 

Definition. — Influenza is an infectious disease occurring in wide- 
spread epidemics and sporadically, believed by many to be due to a 
specific organism, by others to an unknown virus. We shall here discuss 
the known powers of the bacillus and the pathology of the clinical entity 
called influenza with as much of the argument as is pertinent in a book 
of this sort. 

Etiology.' — The Mycobacterium influenza? was discovered by Pfeiffer 
and Canon in 1892. The bacilli are extremely small and usually occur 
singly, though they are occasionally united by the ends, forming short 
chains. They may be stained with the ordinary anilin dyes, especially 
with carbol-fuchsin, but are decolorized by Gram's method. The ends 
of the bacillus are somewhat swollen and usually stain rather more deeply 
than the shaft. This gives the organism somewhat the appearance of a 
diplococcus or dumbbell-shaped bacillus. It is not motile. The bacilli 
will grow only in the presence of hemoglobin and are, therefore, cultivated 
upon glycerin-agar the surface of which has been smeared with rabbit or 
human blood, forming minute dew-drop-like colonies, seen with difficulty 
with the naked eye, but clearly with the aid of a lens. The colonies do 
not coalesce. The appearance of the- growth is somewhat like that 
of condensed moisture on the surface of the culture-medium. 

This organism was first described as the cause of the purulent pneu- 
monia occurring in clinical influenza and was hailed as the virus of the 
disease. Many observers in the great epidemic of 1918 failed to find the 
bacillus in acceptably diagnosed cases so that they refused to believe it 
the etiological agent. During the period between the last two great 
outbreaks in the world, it has been found very seldom as the cause of 
an acute infection like influenza or the "grip" but almost exclusively in 
bronchitis of protracted nature, in bronchiectasis and in pulmonary 
tuberculosis. While the evidence is not conclusive, there are several 
points in favor of its etiological role in the acute disease. To be sure it 
has not been found in every case but the number of instances of clinical- 
influenza in which isolation is successful is much greater in epidemic 
periods than in the interim; it might be said then that it accompanies 
the true virus or is a good indicator of its presence. The proper technique 
for its detection is not as simple as the description would make it appear, 
a good reason for the varying results reported from different quarters. 
Agglutinins, opsonins and complement fixing bodies for the influenza 
bacillus have been found to increase in the blood during favorably 
progressing epidemic cases. 



DISEASES DUE TO BACTERIA 



313 



Arguments against the causative role of the organism include the fail- 
ure of its discovery by many observers either in throat smears and cul- 
tures or lung cultures and histological sections, and the certainty that 
pyogenic cocci are responsible for many complications, pneumonia, 
meningitis and the like. Moreover only one or two successful attempts are 
claimed for the transmission of the disease to lower animals by inoculation 
with the specific bacillus. Further study alone will settle these points. 
It is fair to state that if the influenza bacillus be the cause of the world 
wide pandemic it must be that an especially virulent strain has developed. 

The lesions seen in the bronchi during acute influenza and the chronic 
bronchial changes in which the bacillus seems to have an important 
etiological part, are strikingly similar, a condition which makes us credit 
the influenza bacillus with very distinct influence in the acute disease. 
Compare below lesions in acute influenza and chronic influenzal 
bronchitis. 

The epidemic disease has been ascribed to the effect of filterable 
viruses, non-hemolytic streptococci and a protozoon; there is at present 
no good support for any of these. 

Pathological Lesions Induced by the Influenza Bacillus. — It 

has been generally believed that this organism acts by an endotoxin 
but some observers who credit the bacillus with an etiological importance 
in influenza have discovered that* it elaborates an exotoxin capable of 
causing a febrile reaction and some catarrhal symptoms in lower animals. 
Its effects are expressed in the production of a thick muco-purulent dis- 
charge on mucous surfaces and an exudate of poly- and mono-nuclear 
cells, in which, how ever, the latter type predominates, on serous surfaces 
and within tissue. It is, however, seldom pure on mucous membranes 
or in the lungs, organisms like the pneumococcus and streptococcus 
being present and active, thereby somewhat altering the process. The 
bacilli enter almost exclusively via the respiratory tract and remain local 
for the most part. Instances of pericarditis, meningitis and the like sug- 
gest that hematogenic spread occurs, and it probably does at times, but 
discovery of the bacillus in the blood is so rare that tissue extension by 
contiguity or penetration must be assumed. The organism has 
been found in cranial sinusitis, otitis, meningitis, pleuritis, pericarditis, 
endocarditis, and pneumonitis; the pathology of some of these deservs 
special discussion. 

Influenzal meningitis, arising via the blood or passage of the germ 
through some of the openings of the skull, is of a distinct purulent nature, 
the exudate being greenish and stringy and containing many mononuclear 
cells. The lesions in the pleura and pericardium are similar. Pulmonary 
infections by this organism usually take the form of chronic bronchitis 
with a thick muco-purulent expectoration. The process is chiefly peri- 
bronchial, an exudate of mononuclears invading the submucosa and ad- 
joining alveoli. This inflammation seems to have the power to destroy 
the elasticity of the bronchial wall and, aided by the tenacious secretion 
in the lumen, results in dilatation — bronchiectasis. In our study of 
bronchiectasis of all ages and durations, the influenza bacillus has been 
very frequently in predominance among the cultivable bacteria and has 
seemed to be of value as a vaccine. The invasive purulent peribronchitis 



314 



A TEXT-BOOK OF PATHOLOGY 



extends and is followed by fibrous tissue overgrowth, a change exaggerat- 
ing distortion and dilation of bronchi and leading to irrgeular cavities 
and consolidations. The pulmonary symptoms and signs following in- 
fluenza have repeatedly led to a diagnosis of tuberculosis and only careful 
study with bacteriological research can settle the matter. 

Pathological Characters of Influenza. — The acute disease known 
under this name, or la grippe, is so generally considered as a simple upper 
respiratory tract infection complicated at times by a secondary pneumonia 
that it is well to begin with a clear understanding that such is not the case. 
While the earliest evidences may be catarrhal and the most spectacular 
occurrence is a pneumonia yet there is very early in the attack, a general 
condition usually called a toxemia, which means that the virus spreads 
rapidly through the body. There were deaths during the last epidemic 
so early in the . attack that the pneumonia could not have killed by re- 
spiratory or cardiac embarrassment. In the epidemic of 1890 cardiac 
death was very frequently diagnosed. The autopsies during 1918 revealed 
many lesions that seem peculiar to this disease. In the muscles there is 
Zenker's hyaline change, coagulation necrosis and frequently small 
hemorrhages. On the part of the vascular structures the most striking 
change is congestion, on both sides of the system, with seeping out of 
blood stained serum or actual hemorrhages. Hyaline thrombosis is 
common, leading, it is believed by ..some, to areas of necrosis. The 
heart shows cloudy swelling or hydropic degeneration of its musculature 
and sometimes subserous petechias. The pleurae may be slightly in- 
volved in a mild serofibrinous inflammation but this practically never 
occurs unless pneumonia has spread to the surface; it becomes purulent 
at times principally with the advent of mixed infection. The larynx usu- 
ally exhibits an edema of the mucosa that goes on at times to erosion or 
shallow ulceration. Fibrino-muco-purulent tracheitis and bronchitis 
exists in nearly every case, becoming generalized at times and varying in 
intensity with the duration of the attack, that is being more productive 
in the later stages ; when pneumonia is arising the bronchitis is apt to be 
simply congestive and muco-purulent. Bacteriologically the flora of 
such lungs usually embraces the influenza bacillus, streptococci, pneumo- 
cocci, staphylococci and others and it is very difficult to evaluate the 
importance of any of them. Attempts have been made to describe 
special forms of pneumonitis representative of each of the known pneu- 
monia producers but the result is at present not complete enough for 
exact teaching. The gross appearance of the lungs with pneumonia 
following influenza is of a distended organ, set with areas of pink, red or 
purplish color, separated by emphysematous lung tissue. These areas 
are doughy or quite firm depending upon the degree of consolidation, 
presenting on section a color like that of the pleural surface. Dilated 
bronchi may be seen in the center, filled with pus. The insular consoli- 
dations may coalesce to form a pseudolobar pneumonia. Histologically 
the process varies somewhat with the organisms and cannot be said to be 
uniform. For the most part it is a serofibrinous exudate with moderate 
catarrhal changes in the alveoli but except when streptococci are very 
numerous, polynuclears do not appear in abundance. The bacilli may 
be found by special staining lying within phagocytes but more numerously 



DISEASES DUE TO BACTERIA 



315 



between the mononuclears and in the fibrinoedematous exudate, grouped 
in bunches mostly in parallel arrangement. The characteristic seems 
to lie in the excessive infiltration of the submucous and external coats 
of the bronchi with degeneration of fibers, cartilage and adjoining alveoli, 
thus removing the support of the bronchus which becomes dilated. 
Broncho-pneumonia due to a single variety of organism is always rare 
and the lesion seen in this disease is no exception. However, when 




Fig. 119. — Extreme dilatation of bronchi and softening of the pulmonary tissues. (Norris 
and Landis) {Camp Pike Pneumonia Commission.) 

the influenza bacillus appears as the sole cause of the pneumonitis, it 
acts as the excitant of a bronchitis and peribronchitis of the middle sized 
air passages. 

In the cranial sinuses one almost constantly finds a muco-purulent or 
even sanguino-purulent exudation, which in the later stages may become 
inspissated and dam up the outlet. The meninges show congestion 
and'edema to which may at times be added a definite mononuclear infil- 
trate; pyogenic cocci or even the influenza bacillus may produce a true 
leptomeningitis. Cases of hemorrhagic lepto- and internal pachymen- 
ingitis are on record. Congestion of the brain with small hemorrhages, 



316 



A TEXT-BOOK OF PATHOLOGY 



perivascular infiltration and degeneration of cerebral cells is exceedingly 
common in rapidly fatal cases even without streptococcal or pneumo- 
coccal mixed infection. 

In the lymphatic tissues, notably the spleen, one finds sinus catarrh, 
hyaline degenerations and small necroses; the follicles are very active. 
In the parenchymatous organs, cloudy swellings and focal necroses are 




Fig. 120. — Broncho-pneumonia showing large confluent areas of consolidation. (N orris 
and Landis) (Camp Pike Pneumonia Commission.) 

the rule. A curious complication was met during the last epidemic in the 
form of subcutaneous emphysema usually appearing in the upper thorax 
and spreading all over the body; such cases were usually fatal; no ade- 
quate explanation has as yet been reached. The intestinal lesions con- 
sist of mild catarrhal enteritis but occasionally one finds more or less 
marked petechial hemorrhages and rarely submucous hemorrhagic 
extravasations; the lymphatic nodes are distinctly hyperplastic. 



DISEASES DUE TO BACTERIA 



317 



The lesions just described were found in bodies dying after a very 
short illness and thus represent probably the effect of the virus of in- 
fluenza. Complications in the form of mixed infection with pyogenic 
cocci constantly appear during on epidemic and may modify the picture. 

Clinically the disease is one of rather abrupt onset, short duration and 
rapid decline but the effects are often enduring in the shape of bronchitis, 
sinusitis and asthenia. Its exact means of transmission is not known but 
it is almost certainly via the respiratory tract and if the virus be the 
specific bacillus, it can in most cases be discovered therein. Immunity 




Fig. 121. — Interstitial type of broncho-pneumonia. (Norris and Landis) (Camp Pike 

Pneumonia Commision.) 

is brief for secondary attacks are only too common. An interesting and 
important clinical finding is a marked leucopenia, particularly in unfavor- 
ably progressing pneumonia, when the total count may be as low as 1700 
white cells per cubic millimeter, with 40-60 per cent, mononuclears. 

An acute central nervous system disease called lethargic encephalitis 
is not infrequently seen during influenza epidemics; it will be discussed 
on page 371. 

Organisms Resembling the Influenza Bacillus. — The Koch-Weeks bacillus 
of epidemic conjunctivitis differs in its manner of growth and in the fact 
that hemoglobin is not necessary in the media. It is non-pathogenic for 
animals. Another influenza-like organism found in conjunctivitis is the 
Morax-Axenfeld bacillus (Bacillus lacunatus). This is, however, larger 



318 



A TEXT-BOOK OF PATHOLOGY 



and grows only in the presence of blood or serum, liquefying the latter. 
These two organisms seem specific for the conjunctiva. 

BORDET-GENGOU BACILLUS OF WHOOPING-COUGH 

This organism is now accepted as constantly present in cases of per- 
tussis. According to the studies of Wright, it lies between the cilia of the 
bronchial epithelia, and so interferes with their movements that violent 
efforts to remove it cause the prolonged coughing attacks. By many 
authorities, notably the discoverers of the germ, it is looked upon as the 
cause of the disease, because they can use cultures of it as antigen and fix 
the complement from the hemolytic series. The organism is a minute 
ovoid, sporeless, non-motile, poorly staining, Gram-negative rod. It 
grows aerobically upon media containing glycerin, potato, blood, and 
agar. The effects are due to an endotoxin. Conditions similar to per- 
tussis have been produced in monkeys and dogs by injection and in- 
sufflation of cultures. Agglutinins are said to be formed. Bacterins 
can be used. 




Fig. 122. — Plague or pest bacilli in smear from spleen. 



BUBONIC PLAGUE 

Definition. — The bubonic plague, or pest, is an infectious disease 
due to a peculiar bacillus, Bacterium yestis. 

Etiology. — The bacillus of bubonic plague was discovered by 
Yersin in 1894. In blood drawn from a puncture of the skin and in pus 
from the affected glands may be found small bacilli somewhat resem- 
bling the influenza bacillus. These organisms may be stained readily, 
and often more deeply at the poles than in the center (Fig. 122). This 
gives them an appearance resembling that of the diplococci, and in 



DISEASES DUE TO BACTERIA 



319 



specimens from the blood or tissues there is an indistinct capsule. The 
organism is rather oval in shape, but club-shaped forms are frequent, 
and in cultures long chains are met with. It is not motile; Gram-nega- 
tive; it may live in gelatin between 5° and 20° C. (17° and 68° F.) 
without liquefying the medium. It thrives best in the presence of 
a high degree of moisture. Pure cultures have been obtained upon 
various media. Upon glycerin-agar moist, rounded, whitish, or bluish- 
white colonies are formed. Portions of such colonies removed for 
examination show the bacilli ranged in chains. The growth in bouillon 
is very characteristic, as stalactite formations hanging from the surface 
of the fluid. 

Pathogenicity. — The bacillus has been found pathogenic for mice, 
rats, guinea-pigs, rabbits, and, indeed, any domestic animal; and the 
symptoms produced by pure cultures are the same as those induced 
by inoculating animals with blood or portions of tissues from dieased 
persons. The lymphatic glands may be swollen and petechial hemor- 
rhage may occur as in the human disease. 

Distribution. — In the human being suffering from bubonic plague 
the bacilli are found in the local lesions of the lymphatic glands, the 
buboes, and also in the blood and various organs. Yersin showed 
that flies die of the disease, and succeeded in obtaining the bacillus from 
their dead bodies. They do not flourish in water, but thrive in milk, 
butter, and cheese, and these food-stuffs may spread the contagion. 
The pneumonic form is usually caused by inhalation of droplets of 
sputum from other cases of the same variety, and also by breathing of 
dust that has not dried sufficiently long to destroy the bacteria, but is not 
nec essarily due to inhalation of the germs in all cases. It has been 
shown that the breath during quite respiration of plague pneumonia 
patients does not contain germs, but they are expelled by coughing. 

The rat and its fleas are the chief means of propagation of plague. It 
has been said that plague is primarily a disease of rats, and that man is 
only an accidental host. Transmission from animal to animal and 
animal to man takes place by the rat flea, which will bite man. Bacilli, 
existing in the saliva and digestive tract, may easily be deposited upon 
the surface of an animal or man and rubbed into any small wound of 
the skin, such, for instance, as may be made by the flea-bite. Bacilli 
may also be deposited by fleas or rats upon food or household utensils. 

Not only rats but most rodents are susceptible to plague. Ground 
squirrels of California have been found extensively affected, arid the 
marmot of Tibet is a constant source of infection in that country. 

It is said that mild, unrecognized cases may act as " carriers." 

Pathological Anatomy. — There are three forms of plague according 
to the chief clinical and anatomical manifestations: the bubonic, pneu- 
monic, and septicemic. The organism produces swelling and suppuration 
of lymphatic glands, particularly those of the groin, and, secondarily, 
lesions of internal organs. The lymphatic glands swell quickly, become 
tender and congested, and then soften, forming a rather thick pus. This 
is sometimes blood tinged. Histologically, the exudate is chiefly large 
mononuclears, actively phagocytic of the very numerous pest bacilli. 
This form of exudate soon gives way to necrosis and spread of bacilli 



320 



A TEXT-BOOK OF PATHOLOGY 



outward. Petechial hemorrhages and blood-stained effusions into the 
serous cavities may occur. Petechias of the skin are apt to develop 
as a result of slight traumatisms. Thus, the bite of . an insect, instead 
of producing its usual results, may cause distinct ecchymoses in persons 
suffering from the disease. The pulmonary form produces a bloody 
edematous form of pneumonia; fibrin appears relatively late. This 
may be quite independent of glandular enlargements externally. A 
" septicemic form" is characterized by general infection with wide- 
spread involvement of the lymphatic glands, but without distinct 
buboes. Areas of necrosis take the place of pest abscesses. 

Pathological Physiology. — It seems that the distribution of the 
bacillus in the blood, as well as toxic substances, chiefly endotoxic, 
contribute to the general disturbance of health. By successive inocu- 
lation immunity has been produced, and antitoxic sera have thus been 
obtained. The serum has been used in man with considerable success 
as a protective and also curative agent. It oftens fails in advanced 
cases. 

Haffkine used his method of inoculation as in cholera and obtained 
encouraging results. 

SOFT CHANCRE 

Definition. — The soft chancre or chancroid is an infectious venereal 
sore appearing upon the external genitalia. The bacillus of Ducrey is 
said to be the specific organism. 

Etiology. — The soft chancre occurs almost exclusively upon the 
genital organs or the surrounding parts. It is always caused by direct 
contagion. 

The bacillus of Ducrey and Unna is a rod-shaped organism about 
1.8 n in length and 0.5 in thickness, and appears somewhat com- 
pressed in the middle, so that it has a figure-of-8 shape. The ends are 
rounded and the organisms often occur in chains, or late in the disease 
in pairs, as a diplobacillus. 

The demonstration of the bacillus in the pus is comparatively 
easy. The specimen is stained with alkaline solutions of methylene- 
blue and quickly decolorized with weak acetic acid solution. It may 
be well stained with carbol-fuchsin, alcohol being used to decolorize. 
It is Gram-negative. In the tissues the demonstration is more difficult. 

Growth is most luxuriant in a medium of fresh blood and bouillon, 
but unmixed human blood is the best medium for obtaining cultures 
from a source open to contamination, the fresh blood apparently in- 
hibiting to a certain extent the growth of extraneous organisms. The 
best solid medium consists of 2 parts of alkaline agar and 1 part of fresh 
rabbit's blood if seeded with material obtained by aspiration of a bubo. 
Cultures on ordinary media have thus far been unsuccessful. 

The bacillus is found in the pus of the soft chancre, as well as in 
the deeper parts, lying between the cells and frequently within the 
leukocytes. 

Mixed Infection^ — Various other organisms have been found asso- 
ciated with the bacillus, including streptococci, staphylococci, the 
gonococcus, and bacilli of uncertain nature. 



DISEASES DUE TO BACTERIA 



321 



Pathological Anatomy. — The soft chancre is an ulcer of variable 
character. Usually it is a simple ulcer, with suppurating base and edges, 
not differing from ulcers due to other causes. Sometimes the ulcera- 
tion seems more malignant and takes on a phagedenic or serpiginous 
character (see Ulceration). The neighboring lymphatic glands are 
usually enlarged and sometimes undergo suppurative softening (bubo). 

Pathological Physiology. — Little is known of the existence of special 
toxic bodies in this disease. It is ' believed, however, by some that 
toxins are produced by the bacilli, and that these are capable of pro- 
ducing secondary lesions (bubo) without the presence of the bacilli 
themselves. 

MALTA FEVER 

Synonyms. — Mediterranean Fever; Gibraltar Fever; Febris Undu- 
lans. 

Definition. — -This disease has been described as a form of irregular 
fever occurring along the Mediterranean coasts. It was formerly 
regarded as an aberrant form of typhoid fever, but is certainly 
independent. 

Etiology. — The micro-organism discovered by Bruce, and designated 
Micrococcus melitensis, is by many regarded as the specific cause. This 
is an oval micrococcus about }i n in diameter, occurring singly or in 
pairs, and in cultures as short chains. By Babes it is regarded as a 
bacillus, and certainly agglutinates with more readiness than cocci are 
wont to do. It has no motility of its own. It may be stained with 
ordinary solutions of anilin dyes, but not by Gram's method. It occurs 
abundantly in the spleen, and is usually found in the blood by blood- 
cultures. Pure cultures have been obtained, and inoculation in monkeys 
has seemed to give positive results. Malta fever is not contagious. The 
micro-organisms seem to enter the body through the respiratory or the 
intestinal tract. Agglutination occurs readily with patients' serum, 
and may be used in diagnosis. The organism is excreted in urine and 
milk. The goat, which is used largely for milk supply in Malta, may 
carry the germs and excrete them without being actively infected with 
the disease. 

Pathological Anatomy. — The mucous membrane of the small in- 
testine is red and the solitary follicles and Peyer's patches are some- 
times swollen. The mucosa of the large intestine is generally dark red 
and presents small round or larger irregular ulcerations, from which 
intestinal hemorrhages occur. The spleen is enlarged and hyperemic. 

Pathological Physiology. — Malta fever is characterized by irregular 
febrile movements. The cause of this irregularity and the nature of 
the toxic substance generated in the disease are unknown. 

RHINO SCLEROMA 

This is a disease affecting the skin about the anterior nares and 
adjacent parts, and probably caused by a specific bacillus. The dis- 
ease has been especially observed in central Europe. It presents 
itself in the form of nodular thickening of the skin of the nose and lip, 
and sometimes spreads to the neighboring mucous membranes — mouth, 
.21 



322 



A TEXT-BOOK OF PATHOLOGY 



pharynx, or larynx. In the latter situations ulceration of the surface 
is frequent; the lesions of the skin rarely ulcerate. Histologically, the 
growth consists of round granulation tissue cells. Frequently the cells 
suffer hyaline degeneration, forming rounded hyaline bodies, with 
small granular nuclear masses. These are called Mikulicz cells. The 
bacilli may be found between the cells and within them, especially such 
as present hyaline degeneration. The micro-organism resembles the ba- 
cillus of Friedlander, but by some is said to be Gram-positive. This is 
denied by others. When cultivated upon blood-serum or agar it retains 
its capsule. Inoculation experiments have thus far failed to produce the 
disease in animals. The etiological relationship of the so-called Bac- 
terium rhinoscleromatis is doubted by many observers. 

GLANDERS 

Definition.- — Glanders is an infectious and contagious disease of 
horses and asses, sometimes communicated to other animals and to 
man, and caused by a specific bacillus. 

Etiology.- — The Mycobacterium mallei was first isolated by Loffier 
and Schutz. It is an organism resembling the tubercle bacillus, though 
somewhat shorter and thicker. In cultures it may grow to long fila- 
ments and not rarely it breaks up into coccus-like fragments. It occurs 
m the lesions of the disease singly or in clumps, and has been found in 
the blood. The bacillus is non-motile and does not possess flagella. 
Stained specimens show parts that do not receive the stain. These have 
been regarded as spores, but are more generally thought to be areas of 
degeneration. Ordinary solutions of anilin dyes, and especially alkaline 
solutions, stain the organism very well. The demonstration of the 
bacillus in the tissues requires prolonged staining and rapid decoloriza- 
tion. It is Gram-negative. 

Cultivation.— Cultures are best obtained from softened nodules 
of guinea-pigs inoculated with infected pus, or from the testicles after 
injection of infective matter into the peritoneal cavity. The organism 
grows quite readily upon ordinary media, but the most characteristic 
culture is seen upon boiled potato. The colony first appears as a honey- 
like layer, which becomes brownish in color. The potato itself becomes 
greenish brown beneath and around the colony. The cultivation is most 
successful between 30° and 40° C. (86° and 104° F.). 

Drying and elevated temperatures rapidly destroy the organism, 
and germicides kill it quite readily. The bacillus is a pure parasite, 
multiplying only in the body of infected animals or man. 

Pathogenicity.- — The specific character of the bacillus is unques- 
tionable. Inoculation of guinea-pigs, rabbits, field-mice, or other ani- 
mals with infected pus or with pure cultures leads to nodular lesions at 
the point of introduction, with subsequent softening and ulceration. 
Secondarily, the lymphatic glands enlarge and after from two to four 
weeks suppurate. In male guinea-pigs a practically pathognomonic 
condition (great enlargement of the testicles) is observed within two 
or three days after intraperitoneal inoculation with pure cultures or 
exudate from the lesions of the disease. After death nodules are found 
in the liver, spleen, kidneys, or other organs, and these contain the 



DISEASES DUE TO BACTERIA 



323 



bacilli. In horses and asses characteristic lesions of the mucous mem- 
branes have been produced experimentally; while in man accidental 
infection of hostlers or others coming in contact with diseased animals, 
and of bacteriologists working with cultures, have been repeatedly 
observed. In one case in our own knowledge a man was infected in a 
stable in which a glandered horse was kept, and the bacteriologist who 
isolated the organisms from the patient accidentally infected himself 
with the cultures. The spontaneous infection occurs through some 
abrasion or wound. 

There are two fairly distinct forms of glanders, the acute and chronic. 
The former is septicemic with abscesses, both widely scattered in the 
organs and in the lymphatics of the skin (farcy buds). The term farcy 
is given to the form with subcutaneous abscesses, usually an acute 
condition in man, but commonly more chronic in horses. The chronic 
form is slow of progression, chiefly attacking the lymphatic organs, 
and showing slowly progressive lesions either local or general. 

Pathological Anatomy. — In horses glanders presents characteristic 
lesions of the mucosa of the nose. At first there are found slightly ele- 
vated nodules, which have a marked tendency to soften, forming irreg- 
ular ulcerations that become confluent. The floor and edges of the 
ulcers are yellowish and necrotic in appearance, and discharge more or 
less purulent matter. The lymphatic glands of the neck and elsewhere 
enlarge and may suppurate. In the skin the lesions are much the same, 
but more sluggish. Nodules are not rarely met with in the lungs. 
These are grayish or pinkish in color, and tend to rapid necrosis. More 
rarely nodules or ulcers are found in the mucosa of the gastro-intestinal 
tract. 

In man similar nodules and ulcerations may be found in the nose, 
larynx, or trachea; and external lesions resembling small or large car- 
buncles are found. 

Histologically, the lesions of glanders consist of aggregations of 
round cell of lymphoid or polymorphonuclear type surrounded by a 
zone of spindle and epithelioid cells. Some of the latter swell, and their 
nucleus divides by direct division, causing a kind of giant cell. While 
there is an attempt at tissue reaction it is successful to a certain degree 
only in infections of low virulence, for it is characteristic of the active 
nodule to undergo central necrosis very early. 

Pathological Physiology. — Atoxic substance called mallein (a bac- 
terial protein) has been obtained from cultures of the bacilli. Injected 
into infected animals this acts somewhat as does tuberculin in tubercu- 
losis. A special toxin is probably active in the production of the general 
symptoms of the disease. By repeated dosage with mallein it is claimed 
that immunity may be conferred. The poison of Mycobacterium mallei 
is endotoxic. Agglutinins are produced during an attack, and a com- 
plement-fixing body can be discovered in most cases. 

TETANUS 

Definition. — Tetanus is an acute infectious disease due to a specific 
bacillus, the Bacillus tetani, discovered by Nicolaier and isolated by 
Kitasato. 



324 



A TEXT-BOOK OF PATHOLOGY 



Etiology. — The bacilli occur in the form of cylindrical rods, which 
are frequently swollen at one end, due to the presence of a rounded 
spore (Fig. 123) . They are slightly motile in the vegetative state, being 
supplied with peritrichous flagella; in the spore stage they are non- 
motile. They usually occur singly, though occasionally a few may be 
seen end to end. They occur in the local lesions from which traumatic 
tetanus takes its origin, and may sometimes be readily demonstrated 
by spreading some of the pus or exudate upon a cover-glass and staining 
with the ordinary anilin stains. They also stain by Gram's method. 
The bacillus does not diffuse itself through the body, but in a few cases 
it has been found in the central nervous system. The organism is read- 
ily destroyed by heat, but its spores are quite resistant. 



Cultivation of the tetanus bacillus is difficult. It is obtained from 
garden-earth or the pus of infected wounds by submitting the material 
to sufficient heat to destroy other organisms, even the bacillus of tetanus 
itself, leaving the spores uninjured. "With this material animals are 
inoculated, and from the products of the local lesions or directly from the 
original material cultures are made in gelatin. 

The organism is strictly anaerobic. The typical cultures is obtained 
in the depth of gelatin. Deep beneath the surface there are formed along 
the line of puncture pointed processes standing out at right angles from 
the puncture. After a week liquefaction of the gelatin occurs, and an 
accumulation containing grayish-white turbid liquid is formed. When 
the growth is formed on the surface of gelating in an atmosphere of 
hydrogen a similar radiating structure is found in the colonies, the cen- 
ters of which are rather dense. Liquefaction of the gelatin subsequently 
takes placed. Considerable gas with a pungent odor is produced in the 
growth of this bacillus. 

Distribution^ — The tetanus bacillus is found very frequently in 
garden-earth, in the intestinal discharges of animals, and upon various 



i 




Fig. 123.— Bacillus tetani; X 1000 (Frankel and Pfeiffer.) 



DISEASES DUE TO BACTERIA 



325 



articles about stables. Infection occurs in human beings or animals 
through punctures made by nails, splinters, and the like. 

Pathogenicity.- — The bacillus placed upon an open wound may not 
give rise to the disease, from the fact that the presence of oxygen pre- 
vents its growth. Subcutaneous inoculation, however, causes rapid 
destruction of animals with typical symptoms. The period of incuba- 
tion may be only a few hours, or one or two days, or it may be several 
weeks. The association of certain other organisms, such as the pus- 
producing organisms, seems to favor the development of the disease by 
preventing phagocytic action of leukocytes, or by consuming oxygen 
and thus allowing the tetanus bacillus to flourish. 

The toxin is manufactured in loco and taken up by the nervous 
tissue, for which it has a predilection. 

Pathological Anatomy. — No characteristic lesions are found in this 
disease. Locally, a wound or injury through which inoculation has 
taken place may be discovered; but this is only exceptionally extensive. 
Sometimes no local injury can be discovered, and it is supposed that in- 
fection at times occurs through the gastro-intestinal tract or through 
other mucous membranes. Intense congestion of parts of the nervous 
system and granular degeneration of the anterior spinal motor cells may 
be found at the autopsy, but these are not characteristic. 

Pathological Physiology. — Two distinct toxins have been recog- 
nized — tetanospasmin, which is the predominant poison and that which 
causes the spasms, and tetanolysin, a hemolytic substance of uncertain 
importance. The toxin of tetanus is almost inconceivably poisonous, 
a fact which accounts for the development of a fatal disease in cases in 
which the number of bacilli is minimal. 

The spasmodic seizures first affect the muscles near the point of 
inoculation and in mild infections may be confined to these muscles. 
This has been explained by the experiments of Meyer and Ransom and 
others, who showed that the toxin reaches the nerve-cells of the spinal 
cord by traveling from the muscular end-plates of the motor nerves 
through the axis-cylinders to the cord. The toxin injected into the 
blood does not pass directly to the nerve-centers, but always travels up 
the motor nerves as described. The parts first affected by spasm are, 
therefore, those about the point of inoculation and of elaboration 
of the toxin. 

Tetanus antitoxin has been obtained by successive inoculations of 
animals with the toxin, and in laboratory experiments has been found 
specific and exact in its antagonism to the toxin. In treating the dis- 
ease in man or animals the results have been disappointing, but this is 
now known to be due to the manner in which the toxin and antitoxin 
are respectively distributed and absorbed, and to the fact that the toxin 
has usually reached the vulnerable nerve-centers, and been tightly 
anchored in them, at the time when the antitoxin is injected. The 
antitoxin must be first absorbed by the lymphatics and carried to the 
blood, with which it is distributed to the fluids of the body, whence it is 
again absorbed by the nerves. It is not taken up directly from the 
blood by either the central or peripheral nervous tissue. For these 
reasons the subcutaneous injection of antitoxin fails to effect the neu- 



326 



A TEXT-BOOK OF PATHOLOGY 



tralization of much of the toxin, since the latter is quickly absorbed by 
the peripheral nerves. Intravenous, intraneural, and subdural (spinal) 
injections are more rapid in their effects and, therefore, preferred. 
To prevent combination of toxin and nervous tissue antitoxin must be 
introduced before symptoms arise. It is, therefore, more useful as a pre- 
ventive than as a curative. 

ANTHRAX 

Definition. — Anthrax is a specific infection due to a characteristic 
bacillus. It occurs most frequently in cows and sheep; it may affect 
other animals and man. Dogs, cats, birds, and cold-blooded animals 
are quite immune. In animals it is called splenic fever; in man, malig- 
nant pustule and wool-sorters' disease. 

Etiology. — The Bacterium anthracis was first observed by Pollender 
in 1849, and shown to be the specific cause of anthrax by Davaine in 
1863. In 1879 Koch, Pasteur, and others succeeded in making pure 



'/.*- * M * < % i\ ^ *~ - \, « * » 



5-t 



I* 



Fig. 124. — Bacterium anthracis, stained to show the spores (Frankel and Pfeiffer). 



cultures and in demonstrating their pathogenicity. It was, therefore, 
the first pathogenic organism definitely isolated. The anthrax bacillus 
is a non-motile rod-shaped organism that has a decided tendency to form 
long chains. The individual bacillus is from 5 to 20 ju in length and from 
1 to 1.25 fj. in thickness. The chains appear as threads often with a little 
thickening at the ends of the individual bacilli showing the points of 
contact. The ends are squared or slightly concave. In artificial cul- 
tures in the presence of oxygen spores are formed within the bacilli. 
These are elliptical or oval in shape, and do not alter the configuration 
of the bacillus (Fig. 124). 

The organism is easily stained with the simple anilin dyes, and may 
be demonstrated in the blood or the tissues by Gram's or Weigert's 
stains. There are no flagella. 

Cultivation. — The anthrax bacillus may be obtained in pure culture 
from the diseased organs upon various media. The culture in gelatin 



DISEASES DUE TO BACTERIA 



327 



is most characteristic. Upon plates there are formed whitish colonies, 
which under low powers of the microscope show a tufted, irregular 
character at the edges and upon the surface, suggesting bunches of 
twisted wool-fibers. The gelatin is slightly liquefied. The tufts may be 
removed by pressing a cover-glass against the surface of the colony, and 
when stained are found to consist of curved parallel chains of bacilli. 
In puncture-cultures filaments project at right angles to the puncture 
toward the sides of the test-tube, and the growth at the surface, where 
oxygen is abundant, is luxuriant, while that in the depth is compara- 
tively sparse. 

Pathogenicity. — The infectiveness of the bacillus is undoubted. 
A small portion introduced into a susceptible animal gives rise to marked 
symptoms in twelve or twenty-four hours, and death soon follows. 
The bacilli may be demonstrated in the blood and in various organs 
in great abundance. When the bacillus is killed and the spores are intro- 
duced into the body similar results follow. The spores are highly 
resistant and may preserve their virulence for years. Sporeless varie- 
ties of anthrax bacilli have been encountered and have been produced 
by cultivation under unfavorable conditions. 

Distribution. — The anthrax bacillus occurs in all of the local lesions, 
and from these is carried into the blood and the organs, particularly 
the spleen, liver, kidneys, and lungs, where it is found in the capillaries 
in immense numbers. The structure of these organs is, as a rule, little 
affected, probably because death occurs before changes can take place. 
The organisms may be present in only small numbers in the blood of the 
general circulation when the capillaries of the various organs are filled 
with them. The organisms are discharged from the body in the stools, 
urine, and other discharges, and are thus conveyed to other animals. 
At one time it was supposed that they were scattered about by earth 
worms obtaining them from cadavers; this is scarcely probable. Mul- 
tiplication of the organisms outside the body does not occur to any 
extent, but the organisms, and particularly the spores, may live a long 
time, and may be conveyed to great distances in infected materials, 
particularly wool, hides, bristles, and the like. 

Mode of Infection. — In animals infection most frequently occurs 
through the gastro-intestinal tract, the bacilli being swallowed with 
fodder that has been contaminated. The organisms may, however, 
gain entrance through the lungs or through external abrasions. The 
latter form of infection is most common in man, though gastro-intestinal 
and pulmonary infection sometimes occur; a considerable number of 
malignant pustules have been observed about the face and neck of men 
using shaving brushes made of imperfectly sterilized bristles. 

Pathological Anatomy. — The lesions produced by anthrax are more 
or less local, but occasionally are septicemic. In man, after infection 
of the skin through abrasions in persons handling the hides or wool or 
other materials from diseased ammals, a swelling of greater or less size 
develops. This is intensely inflammatory, often covered and surrounded 
by slight bullous vesicles, and attended with considerable edema. Ero- 
sion of the surface may take place and sanious liquid may be discharged, 
with the formation of crusts. Histologically, the process consists of 



328 



A TEXT-BOOK OF PATHOLOGY 



rapid infiltration of the corium and papillary bodies with leukocytes. 
The bacilli are found in abundance between the cells, and hemorrhagic 
infiltration and serosanguinolent edema are observed. Necrosis sub- 
sequently occurs, though not to a considerable extent. When infection 
takes place through the gastro-intestinal tract, as is sometimes ob- 
served in man and very commonly in animals, lesions somewhat like the 
above are formed in the mucosa and submucosa of the small intestine, 
less frequently of other parts. At first these lesions appear as hemor- 
rhagic extravasations, then swelling follows, and finally the surface 
ulcerates, leaving irregular excavations with blood-stained bases and 
edges. Profuse diarrhea with bloody discharges may occur. Infection 
through the lungs occurs in men engaged in handling infected wool 
(wool-sorters' disease), and in persons working in paper factories, where 
infected rags carry the germs. In these instances the bacilli lodge in the 
alveoli of the lungs, causing rapid cellular exudation with considerable 
edema and hemorrhagic infiltration. The process is lobular in character, 
but large areas of the lungs may be simultaneously involved. Sero- 
sanguinolent pleurisy, swelling of the lymphatic glands of the medias- 
tinum, and hemorrhagic extravasations of the mediastinum are not 
unusual. In all forms there is acute inflammatory or hemorrhagic 
swelling of the spleen. 

Pathological Physiology. — The presence of the anthrax bacillus 
probably leads to the formation of toxic materials in the blood, although 
while a poisonous albumose has been obtained from cultures, its nature 
is not understood and its identity doubted by some. The general 
symptoms, however, are probably in large measure the result of dis- 
semination of the bacilli themselves and their local effects. 

Their action seems to be directed primarily against the circulatory 
system, as the toxin calls forth leakage of serum and escape of blood. 
Much fibrin is formed, but there is little tendency to cellular accumu- 
lation or suppuration. 

It has been found possible by cultivation at high temperatures, 
by introducing the organisms into insusceptible animals, and also by 
adding chemical agents to cultures to alter the pathogenicity of the 
bacillus to such an extent as to make it harmless, even to white mice. 
By introduction of such cultures and subsequent successive inoculation 
with cultures of increasing virulence protection has been afforded. 
Antitoxic substances have been obtained from the blood of protected 
animals, and the use of such serum locally and into the circulation seems 
to have been followed, in some cases of local anthrax, by distinct 
benefit. In animals protective vaccination with asporogenous cultures 
is much more profitable than serum therapy of established infections. 

MALIGNANT EDEMA 

Definition. — Malignant edema is a form of intense infective in- 
flammation and necrosis observed in certain animals and in man, and 
is due to a specific micro-organism. The condition has frequently 
been described by clinicians as gaseous gangrene, traumatic gangrene, 
gangrene foudroyante, etc. Infectious emphysema (q. v.) has doubt- 
less often been mistaken for this disease. 



DISEASES DUE TO BACTERIA 



329 




Etiology. — The micro-organism of malignant edema was described 
by Pasteur and named the Vibrion septique. Koch showed that it does 
not flourish in the blood, and that the name given by Pasteur is, there- 
fore, not appropriate. He, therefore, named it Bacillus oedematis maligni. 
This organism is widely distributed. It is very commonly present in 
the soil, particularly in garden-earth, and is often found in dust and in 
the intestinal contents of animals. Introduced into the subcutaneous 
tissue of animals it multiplies greatly and sets up a violent local process. 
The bacilli are readily obtained from the diseased area, and may be stained 
with the ordinary anilin dyes, but not by Gram's method. The bacillus 
resembles the anthrax bacillus very closely, but is 
somewhat more slender. It is prone to occur in 
pairs or in chains or long filaments, the several bacilli 
being joined end to end. Movement of the organisms 
is frequently observed, and lateral flagella are found 
by appropriate stains. In the spore formation the 
center of the organism swells and the spore is developed 
within. 

The cultivation of this organism is generally easy. 
White mice or other susceptible animals are first 
infected by introducing powdered garden-earth into 
a subcutaneous sac. Direct infection of an open 
wound will not succeed, as the organism is strictly 
anaerobic. 

From the pus in the subcutaneous tissues growths 
may be obtained upon the surface of gelatin in an 
atmosphere of hydrogen, or in puncture-cultures in 
gelatin from which oxygen has been excluded. On 
the surface of the gelatin are formed small grayish- 
white bodies, which increase in size with advancing 
age. Portions removed from these and stained 
show masses of bacilli in the form of long filaments. 
In the gelatin-tube there are formed whitish spherical 
colonies of a somewhat cloudy appearance. These fig. 125— Bacillus 
consist of a turbid liquid, the gelatin undergoing of malignant edema 
liquefaction. There is also some gas production, the geLTi^CFrank^and 
gas formed having a peculiar and unpleasant odor. This Pfeiffer) . 
is marked when the medium contains glucose (Fig. 125) . 

Distribution. — The bacillus of malignant edema occurs only in the 
subcutaneous tissues near the point of inoculation, in the muscles, and 
in the peritoneal cavity at the time of death. It does not invade the 
blood, as the amount of oxygen there present prevents its growth, and 
it flourishes in the subcutaneous tissue because this is least accessible 
to oxygen. In bodies dead some time the organism may spread to the 
blood and the organs of the body. The distribution of the organisms 
outside the body has been referred to. 

Pathogenicity. — The bacillus of malignant edema is undoubtedly the 
cause of the disease in question, as has been proved by inoculations upon 
mice, guinea-pigs, and other animals. Cats and dogs are less susceptible 
than other animals; cattle seem to be almost wholly immune. 



r 1 



330 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — The lesions of malignant edema consist of 
various forms of rapid suppuration and necrotic inflammation of the 
subcutaneous tissues. These may rapidly form emphysematous and 
gangrenous alterations of the subcutaneous tissues, with sometimes 
pus formation, at other times extensive hemorrhagic infiltration. 

Pathological Physiology. — Toxins are doubtless formed, but these 
have not as yet received special attention. Artificial immunity has been 
secured by injections of sterilized cultures of the bacillus in bouillon, 
and by other methods. A few cases of malignant edema have been re- 
ported in man, some following injection of musk in the course of typhoid 
fever, some occurring in the puerperium, and some apparently without 
external injury. Infection in the latter probably occurred from the 
mucous surfaces. In all cases the general vitality of the patient was 
reduced by some previous disease. 

INFECTIOUS EMPHYSEMA OR GASEOUS EDEMA 

Definition. — These are the present terms applied to a form of infec- 
tion that has been described under various names, such as gaseous 
gangrene, gas phlegmon, emphysematous necrosis, and the like. Un- 
doubtedly it has been mistaken for malignant edema in certain cases. 
The disease is caused by the Bacillus aerogenes capsulatus of Welch and 
Nuttall; it is also called Bacillus perfringens. 

Etiology. — The bacillus in question is a non-motile organism of 
variable size, 3 to 6 ju. in length, and about the thickness of an anthrax 
bacillus, with adjacent ends slightly rounded or square cut, and occur- 
ring singly, in pairs, clumps, or sometimes in short chains. Very rarely 
it occurs in long threads. It is easily stained with the ordinary anilin 
dyes or Gram's stain. A capsule is sometimes demonstrable in specimens 
obtained from the body or from agar-cultures. 

Cultivation^ — The organism is anaerobic, no growth occurring on 
the surface of solid media in the presence of oxygen. In media contain- 
ing fermentable material gas formation is regularly observed. The 
colonies in agar are grayish-white or slightly brownish, those in the 
depth appearing as small spheres or ovals slightly flattened, with knob- 
like or feathery projections. The cultures in gelatin show slight and 
slowly developing liquefaction. 

Pathogenicity. — By experiments on animals exactly the same lesions 
are produced as those found in man. The action of the bacterium has 
been ascribed primarily to its power to grow upon devitalized tissue with 
the production of gas and acid, the latter being absorbed and causing 
acidosis. Considerable weight should be given the recent demonstration 
of a small quantity of exotoxin formed by this germ. The toxin has 
moreover a local necrotizing effect in the tissue of experimental animals. 
The power of this organism is greatly enhanced by mixed infections 
with aerobes. Mixed infection of anaerobes often occurs. 

Pathological Anatomy. — The first noticeable local lesion is a doughy 
swelling of bluish appearance; very shortly crackling may be elicited. 
This swelling consists of sanguinolent edema and gas bubbles, which 
latter split open fascial and muscle planes allowing the various bac- 
teria to spread. The entire surface of the body sometimes becomes 



DISEASES DUE TO BACTERIA 



331 



emphysematous, and at the autopsy the organs, especially the myo- 
cardium, kidneys, liver, and spleen, present a characteristic appearance. 
They are lighter in color, and on inspection are found to be filled with 
vacuoles or gas-bubbles. The blood of the heart and vessels presents a 
foamy condition, due to the gas formation. Practically, any of the 
tissues of the body may be affected. Microscopically, the occurrence 
of gas- vesicles with numerous bacilli in their walls is the most striking 
feature. 

Regarding the mode of infection, it seems likely that in all cases 
the organisms enter through some injury or abrasion connected with the 
external world. Some cases have followed traumatic injuries, others 
occur in connection with disease marked by ulcerations of the surface 




Fig. 126. — Bacillus aerogenes capsulatus (McFarland, from photograph by Prof. Simon 

Flexner) . 

of mucous membranes, and at least one instance has been carefully 
studied in which the disease occurred during the puerperium, probably 
due to uterine infection. It is not improbable that some of the cases 
of supposed air-embolism from douching of the uterus after labor are, in 
reality, cases of this form of infection. 

The two foregoing conditions are given as the expression of pathogene- 
sis of the two principal representatives of the anaerobic bacteria, very 
many of which have been described varying in minor morphological 
and biological characters. Other important forms are named Bacillus 
sporogenes, Bacillus putrificus coli, Bacillus phlegmones emphysema- 
tosa, Bacillus histolyticus. All these bacteria inhabit the soil and 
have been found in the human and animal intestinal tract. It has been 
proposed that those of them whose activities include proteolysis, are 
responsible for intestinal putrefaction with constitutional effects such 
as anemia; this assumption has not been confirmed. The group has 
grown in importance and been widely studied because of the large 
numbers of gas gangrene cases during the late war. The highly cul- 
tivated soil of France was loaded with all the members of the group so 
that their entrance into wounds on bits of clothing and shell was simple. 



332 



A TEXT-BOOK OF PATHOLOGY 



The devitalization of tissue by the injury and the oxygen-binding power 
of aerobic germs introduced at the same time, permitted the anaerobes 
to produce their characteristic gaseous and necrotizing gangrene. Where 
wounds were operated upon shortly after their reception, gas infection 
was much reduced, showing that the maceration of tissue favored 
anaerobic growth. An antitoxin has been prepared for prophylaxis but 
its use has not been followed by perfectly satisfactory results. 

TUBERCULOSIS 

Definition. — The term u tuberculosis " refers to various condi- 
tions due to infection with the tubercle bacillus, Mycobacterium tubercu- 
losis, no matter what the form or individual peculiarities of the case. 
The name was originally employed because of the occurrence of small 
nodules or " tubercles." It must be remembered, however, that other 
diseases show small miliary nodules, perhaps indistinguishable to the 
naked eye from miliary tubercles, and that tuberculosis sometimes 
occurs without a single definite tubercle. 1 

Etiology. — Tuberculosis is infectious and contagious, the bacilli 
being transferred by the secretions and excretions from diseased per- 
sons to a susceptible individual through the air, food, drink, or in other 
ways. The infectious character of the disease was long suspected, 
but was definitely proved by Villemin in 1865, and in 1882 Koch suc- 
ceeded in isolating the infective bacillus. Predisposing causes are of 
some importance. Formerly family susceptibility was thought an all- 
important cause, and the disease was supposed to be transmitted directly 
in families. At the present time we recognize the transmission of 
susceptibility, and very rarely transmission of the disease itself, from 
parent to child. Warthin has found cases in" literature and his own 
observation where direct transplacental passage of tubercle bacilli has 
occurred, both with or without lesions in the placenta. Tubercle bacilli 
have been found in the semen. (See Placenta.) Susceptible persons 
frequently show delicate organization with poor development of the 
body, particularly of the chest. When this susceptibility or predis- 
position exists, there is naturally greater receptivity for bacilli spread 
around by tuberculous associates. Besides inherited susceptibility, 
acquired predisposition may result from occupations which lower vitality, 
from grief, prolonged nervous strain, and exhaustion; and some one of 
the organs may be specially predisposed by injuries. Such mechanical 
lesions prepare a place of lesser resistance, and tubercle bacilli more easily 
gain a footing than in normal tissues. Continued local anemia seems to 
predispose. 

The human tubercle bacillus is a rod-shaped organism, 1.5 to 3.5 m 
in length and from 0.2 to 0.5 /j. in breadth. Sometimes it is even longer, 
especially after cultivation. It often occurs in pairs or in groups arranged 
end to end, but not overlapping, and evidently not attached the one 
to the other. It also occurs either straight or more or less curved, and 
may often be found S-shaped or in branching forms. When stained, it 

1 In this book the adjective "tuberculous" applies to the specific disease caused by 
the bacillus of Koch, other conditions being called "tubercular." 



DISEASES DUE TO BACTEEIA 



333 



may either appear uniformly colored or may present a beaded appear- 
ance, regarded by some as due to spores, a view that has not been proved. 
The condition is caused by the alternation of portions well stained 
and intervening parts with little or no stain (Fig. 127). These light 
areas, formerly regarded as spores (Koch), are now believed to be the 
result of fragmentation of the bacillus and retraction of the substance 
of the organism causing vacant areas. There appears to be *a narrow 
capsule closely applied to the organism, and the capsule seems to con- 
tain in especial abundance the wax-like substance that occasions the 
peculiar acid-fast staining properties of the bacillus. The bacillus is 
non-motile and does not have nagella. 

The tubercle bacilli found in man, cattle, and fowl exhibi struc- 
tural and cultural differences, though they are probably the same bacilli 
exhibiting different characteristics caused by their growth in different 
environments. 




Fig. 127. — Tubercle bacilli in the sputum; Zeiss's homog. immersion ]/[ 2> Oc. 4; magnified 

about 1000 diam. 

The bovine bacillus is much shorter and thicker than the human 
bacillus, being from 1.5 to 2 ju in length and of an oval shape, the length 
being not more than double the breadth. It is straight, and does not 
exhibit the curved and branching forms of the human bacilli. When 
stained, it is more uniformly colored, the beading being usually absent. 
Cultures of the bovine organism in glycerin broth are at first acid, but 
become alkaline, while those of the human species never become alkaline. 
Tuberculin made from the bovine species is alkaline; that from the 
human species is highly acid. 

The human type is more easily grown. The bovine type will infect 
rabbits uniformly, while great quantities of human culture are necessary. 
Human bacilli will not infect calves with progressive lesions. 

The avian tubercle bacillus differs from the human bacillus in that 
it is more often club shaped and branching, and that it grows more 
luxuriantly upon glycerin-agar and blood-serum, and at a much higher 
temperature — 45° C. (113° F.). It will also grow on ordinary agar, 
but not on potato. It is much more resistant to heat, especially as re- 
gards its virulence. It will not infect guinea-pigs with a progressive 
lesion. 



334 



A TEXT-BOOK OF PATHOLOGY 



Artificial culture of the Mycobacterium tuberculosis was first success- 
fully accomplished by the use of blood-serum as a medium. The bacillus 
grows very slowly; after ten days or two weeks the surface of the medium 
shows dry flakish deposits, somewhat resembling the scales in certain 
skin diseases (Fig. 128). The edges of these flakes tend to elevate them- 
selves a little, and the substance of the growth has a crumbled appear- 
ance. Placed under a cover-glass in mass and examined with the 
microscope these flakes are found to be composed of contorted masses 
of bacilli (Fig. 129). Pure cultures are best ob- 
tained from the lymphatic glands of animals 
artificially infected and destroyed before the 
tuberculous foci have advanced to the stage of 
necrotic change. Cultures may be obtained 
with some difficulty from the sputum or other 
/ » ff.-i excreta. At the present time blood-serum is 




Fig. 128. — Culture of tu- Fig. 129. — Bacillus tuberculosis; adhesive cover-glass 

bercle bacilli on glycerin-agar, preparation from a fourteen-day-old blood-serum culture; 
four weeks old (Frankel and X 100 (Frankel and Pfeiffer). 
Pfeiffer). 

less frequently used, as it has been found that agar-agar slightly acidulated 
and containing a large proportion of glycerin, and bouillon containing 
glycerin, serve as useful media. The original culture is still, as a rule, 
obtained on blood-serum or coagulated egg. Even potato and other 
simple substances aie found to be satisfactory media. The bacillus 
requires a rather even temperature for its growth : it flourishes best a 
37.5° C. (99.5° F.), and does not grow below 29° C. (84° F.) or above 
42° C. (107.6° F.). Exposure to higher temperatures (75° C; 167° _F.) 
rapidly destroys it, and strong sunlight is destructive. It requires 
considerable air and best grows upon the surface of the medium in 
which it is cultivated. Prolonged cultivation upon artificial media 
lessens its virulence. 

The demonstration of the tubercle bacillus by staining methods is 
usually simple and satisfactory. It has been found that this organism, 



DISEASES DUE TO BACTERIA 



335 



like that of lepra and the smegma bacillus, does not readily stain, but 
after receiving a stain retains it despite the action of strong mineral 
acids. Upon this principle the methods of staining are based. The 
procedure requires the addition of a mordaunt which will fix the stain 
in the bacillus, anilin oil and phenol being the ones in common use. After 
the dye and mordaunt have acted for a sufficient length of time, pro- 
longed immersion in alcohol and acids will not remove the coloring 
matter from the tubercle bacillus but all tissue and other bacteria are 
decolorized, permitting the use of a counterstain for their demonstration. 
This "acid fast" property seems to lie in the wax of the organism, 
distributed in its body and capsule. The method outlined is applicable 
to tuberculous excreta (sputum) or to morbid tissue (pathological sections 
of lungs, glands, etc.). At times it is extremely difficult to find the 
organisms because they are scarce or have undergone a granular de- 
generation. A special technique (the Much-Gram stain) has been devised 
but it can hardly be said to be entirely dependable so that one is driven 
to inoculating the morbid material into guinea-pigs, in which animals 
lesions appear in from a few days to six weeks because they have little 
or no resistance to the organism. The reader is referred to books on 
bacteriology for the details of the above method. 

Distribution of the Tubercle Bacillus. — This organism is probably 
a pure parasite, occurring and multiplying only in the body or excreta of 
diseased individuals, human or animal. Sputa or other excreta contain- 
ing the bacillus may dry and retain the bacillus in a dormant though still 
potential form for long periods of time, outside the body. Multiplication 
of the organism, however, probably very rarely occurs, except within 
the body. The bacillus is found in the lesions of all parts of the body. 

Modes of Infection. — The bacillus may gain access to the body either 
by direct inoculation, by the inhalation or swallowing of the germs, or 
by intra-uterine transference through the placenta. Direct inoculation 
through external wounds is perhaps more frequent than is believed. 
Definite lesions of the skin have been caused by vaccination, and are 
not infrequent upon the hands of anatomists in the form of the so-called 
anatomical tubercles. In some of the cases of scrofulous glands of the 
neck in children it is likely that the bacillus gains entrance through 
abrasions of the skin or of the mucous membrane of the mouth or pharynx. 
Genital tuberculosis is quite possibly frequently produced by direct 
implantation. The most common form of infection is through the 
inspired air. The breath of phthisical patients does not ordinarily 
contain bacilli, but the dust of rooms in which tuberculous patients have 
lived may contain numerous bacilli in a dry state, and these 
readily become mixed with the air and are thus inhaled. It was shown 
long ago that the coughing consumptive discharges visible and invisible 
droplets containing perfectly enormous numbers of tubercle bacilli so that 
it is easily conceived how generally the air and contents of a room may be 
contaminated if the patient be careless about covering his mouth while 
coughing. Tuberculosis of the lungs or, more rarely, of other parts of 
the respiratory tract is thus produced in susceptible persons. Despite 
the activity of some investigators to inculpate the intestinal tract in the 
origin of all lung lesions, it is now generally accepted that most pulmonary 



336 



A TEXT-BOOK OF PATHOLOGY 



tuberculosis arises by inhalation. Experimental support for this is 
found in the ease with which pulmonary lesions may be induced in 
animals by inhalation and by the discovery that it requires many 
thousand times more of ingested bacilli to cause them. The bacilli 
lodge upon the mucosa, are taken into it, or by lymph-radicals, and 
carried to nearby lymph-nodes. Occasionally they reach the smaller 
bronchi and start the lesion there. The swallowing of tuberculous 
material may lead to tuberculosis of any part of the gastro-intestinal 
tract by the direct inoculation that results. Thus intestinal tuberculosis 
in particular is produced. Sometimes, however, the bacilli pass through 
the wall of the intestine and cause a primary lesion in the lymphatic 
glands of the abdomen, and it is not improbable that even the mesenteric 
lymphatic glands may escape without discoverable lesion or wholly, 
and the final lodgment of the infecting organism may [be the lungs 
The bacilli are swallowed with milk or meat, or they may gain access 
to the mouth, in the form of dust or particles of various kinds, and be 
swallowed with the saliva. Some assert that tuberculosis of the tonsil 
is of alimentary origin. 

The milk and meat of infected cattle frequently contain bacilli, 
and undoubted instances of infection in this way have occurred. The 
proof of this is that in some cases of abdominal tuberculosis in young 
children the organisms obtained in cultures, have shown the character- 
istics of the bovine species. 

v. Behring taught that tuberculosis was acquired in childhood and 
remained latent until adult life; this view has not been widely accepted. 
Interesting statistics from Norway indicate, however, that more con- 
sumptives give a history of having been exposed to infected individuals 
during their childhood than an equal number of nontuberculous persons, 
by four to one. 

The intra-uterine transmission of tuberculosis is rare, but does occur. 
Most of the cases, however, of tuberculosis in early life may be ex- 
plained as postnatal infections through milk, inspired air, etc. Some 
authorities assume that a few tubercle bacilli transferred from the 
mother to the fetus may lie dormant in the fetus and child and later 
cause active infection. This hypothesis rests upon no demonstrated 
facts. 

Relation of Human to Animal Tuberculosis. — Tuberculosis attacks 
the lower animals with varying frequency. It is most common in 
cattle, and because of the peculiarities of the bacilli and lesions this 
form of the disease is termed " bovine tuberculosis." Many experi- 
ments have been made to establish the relation existing between the 
bovine and human forms of the disease, and Koch, in 1901, made the 
statement that the two were different diseases and probably were not 
intercommunicable. Ravenel disproved this assertion by producing 
the disease in cattle with bacilli obtained from human sources, although 
the animals exhibited a high grade of resistance to such an infection. 
At the same time he reported 4 cases of accidental local infection in 
man with the bovine bacillus. He, therefore, maintains "that human 
and bovine tuberculosis are but slightly different manifestations of one 
and the same disease, and that they are intercommunicable." 



DISEASES DUE TO BACTERIA 



337 



The present situation of the subject is best illustrated by the results 
of Park and Krumwiede. After exhaustive studies of the literature and 
their own material, these authors conclude that while bovine infection 
for the adult is practically negligible, in children a noteworthy per- 
centage of tuberculosis of glands, abdominal organs, and meninges is 
due to the bovine tubercle bacillus. There is no positive proof now at 
hand to show a mutation from one type to the other. 

Less frequently tuberculosis occurs in hogs, goats, horses, dogs, cats, 
sheep, rats, guinea-pigs, and rabbits. All these animals are more 
susceptible when kept in confinement. Captive monkeys are highly 
susceptible. In all these animals the disease is probably intercom- 
municable with human tuberculosis, but the lesions are not always 
identical with those found in the latter disease. Fowl of various kinds 
are susceptible, though the disease is somewhat different in them from that 
seen in man. (See Fowl-tuberculosis.) Tuberculosis of cold-blooded 
animals has also been recognized. The form of disease in the latter 
is atypical, and the bacillus shows peculiar characteristics, but tends to 
approach the form of the human bacillus by successive passage through 
animals. 

The method of transmission of the disease from lower animals to 
man is chiefly through the use of infected milk and meat. 

According to the best testimony available at the present time it 
seems likely that the human, bovine, avian, and other animal species 
are simply variations of one common bacterial organism. Not im- 
probably the peculiar characteristics may be acquired in the human 
body or the animal after the original infection. Thus the proof of the 
original source of the infection may be lost. 

Pathological Anatomy. — -Tuberculosis is characterized by the erup- 
tion of small nodules, varying in size from 1 to 2 mm. in diameter to 
that of a small pea. These are known as miliary tubercles. As already 
mentioned, the latter in gross appearance are not distinctive of tuber- 
culosis, as similar nodules are met with in other diseases. Besides the 
tubercle there are inflammatory lesions occurring between the tubercles 
and varying with the anatomical character of the organs affected. Thus 
in the lungs the tubercle may be inconspicuous, whereas the pneumonic 
infiltration of the lung tissue . surrounding the tubercles and filling in 
the spaces between them gives the organ its most striking anatomical 
characters. There are instances of tuberculosis in which the whole 
process runs its course without the development of any definite tuber- 
cles — acute tuberculous inflammation. For example, in the lungs 
the inhalation of tubercle bacilli in considerable numbers may be followed 
by rapid tuberculous pneumonia without definite tubercles, and in other 
situations similar results may be produced. In the further progress of 
a case of tuberculosis caseous change is important. This may present 
itself in the form of areas of considerable size having a dull, opaque, 
lusterless, grayish or whitish character, and not inaptly likened to the 
appearance of cheese. These centers of caseous necrosis may finally 
become liquefied, and cavity formations may result. These changes 
are particularly frequent in tuberculosis of the lungs, less frequent in 
bones, skin, glands, or kidneys. Under such circumstances one has 



338 



A TEXT-BOOK OF PATHOLOGY 



usually to do with a mixed infection of pyogenic cocci, the action of which 
will materially alter the process by adding true suppuration. The 
ulceration of tissue by these bacteria aids the extension of caseation, 
coalescence of neighboring foci and a liability of involvement of blood- 
vessels. In connection with tuberculosis of bones there may be formed 
small or large cavities filled with liquefied caseous or puriform material. 
These may involve the surrounding tissues as well as the bones them- 
selves. The term "cold abscess" is applied to them. Small tuberculous 
areas and sometimes even large foci are prone to be surrounded by 
reactive fibrous-tissue hyperplasia, and thus a complete encapsulation 
may result. Small foci may be uniformly transformed by organization of 
proliferating connective tissue and may be thus entirely healed. In 
other cases simple encapsulation occurs, the tuberculous mass within 
perhaps undergoing calcification. These changes will be more particu- 
larly referred to below. 

Tuberculous lesions of the mucous membranes frequently begin with 
the formation of distinct tubercles occupying the deeper layers of the 
mucosa or the submucosa. These by confluence may form considerable 
areas of tuberculous disease, while at the same time reactive inflammation 
of the surrounding tissues adds to the mass. Sooner or later ulcerative 
changes upon the surface make their appearance, and irregular, more 
or less necrotic, ulcers result. The caseous appearance of these and 
the occurrence of distinct tubercles in the edges or base manifest the 
character of the process. 

The histogenesis and anatomy of the tubercle has been considered 
on page 147, and we shall only here consider its pathological relations. 

After the establishment of the local lesion of tuberculosis in any 
part of the body two opposing tendencies struggle for supremacy: the 
tendency of the tuberculous disease to spread and the tendency of the 
normal tissues to encapsulate or limit the spread of the invading disease. 
In most cases the former succeeds and the secondary tubercles first 
appear in adjacent parts, the transportation of the bacilli from the 
primary to the secondary focus being accomplished either by the flow 
of the lymph or juices of the body, by continuity, or by the activity 
of phagocytes. The last take from the edges of the tubercle some 
of the bacilli and transport them either by their own ameboid activi- 
ties or in the lymph-stream to neighboring parts, where they them- 
selves fall victims to the organisms they have appropriated, and thus 
deposit the germs of new foci of disease. The dissemination of tuber- 
cles to more distant parts may occur in various ways. In the case of 
tuberculosis of the mucous membranes bacilli may be cast off from the 
surface and spread to other parts of the mucous tracts with the contents 
of these, as in the case of tuberculosis of the gastro-intestinal tract. In 
the case of pulmonary lesions the ulcerative processes, or attacks of 
coughing, may loosen infected particles from lesions of the bronchi, 
and the deep inspiratory efforts following the cough, or the ordinary 
inspirations, may carry the bacilli into the finer bronchioles, where new 
foci arise. If the tuberculous lesions involve the walls of the lymphatics, 
particularly the larger lymph-channels, like the cervical or thoracic 
ducts, bacilli may gain access to the lymph-stream and thus be trans- 



DISEASES DUE TO BACTERIA 



339 



ported to the venous circulation, and then through the heart to the lungs 
or perhaps to other organs. When the tuberculous lesion invades the 
wall of a vein the dissemination of the bacilli is even more rapid and 
widespread, as the organisms find their way to the heart by a more 
direct route. In rare instances an artery is invaded and the organisms 
are scattered through the terminal distribution of this. The lesions 
of vessel walls arise either as primary tubercles, as extension processes, 
or secondary to intimal lesions leading to thrombosis, a condition which 
favors the settling of tubercle bacilli. Upon surfaces the disease may 
spread by direct continuity or by the movements of the body. Thus, 
lesions of the peritoneum may become almost universal in consequence 
of the peristaltic movements, though more frequently the extension 
occurs along the lymphatic channels. 

The condition which results from general infection and formation 
of tubercles in various situations is known as miliary tuberculosis. In 
these cases the progress is usually rapid and a fatal termination is not 
long delayed. The tubercles, therefore, remain small, and at autopsy 
are still typically gray miliary tubercles. Sometimes, however, miliary 
tuberculosis may assume a more chronic form, perhaps in consequence 
of the gradual admission of bacilli to the circulation and the formation 
of small crops of tubercles during a considerable period of time. 

Occasionally, tubercle bacilli invade the blood and do not give rise 
to miliary tuberculosis. Why they do not is not clear. 

Miliary tuberculosis may be local or general. In the former case 
the bacilli are admitted to the vascular distribution of a restricted 
area only; in the latter, widespread dissemination through the blood 
occurs, and practically all parts of the body may be involved. Local- 
ized miliary tuberculosis is most frequent in the lungs. 

The progression of tuberculosis is accomplished by the coalescing 
of formed tubercles or an exaggeration of the inflammatory characters, 
especially in the presence of mixed infection, or to both. Regressive 
tuberculosis is either latent (q. v.) or cicatrizing. The latter is that 
form in which the most pronounced lesion is fibrous tissue formation, 
which may or may not finally wholly replace the tuberculous tissue. 
Such a process is responsible for the healing of tuberculosis. It has 
been asserted that two-thirds of all adults have some such healed lesion 
of tuberculosis in them. 

The healing of tuberculous lesions follows the general rules of repair. 
The fibroblasts grow both within and without the tubercle and gradu- 
ally replace it. Wherever fibrin has been deposited the tubercle grows 
and attempts to form a new tubercle. It is noteworthy that in healing 
of tuberculosis a great amount of fibrous tissue is produced and ad- 
hesions are common. 

Seats of Tuberculosis. — -Among the frequent situations in which 
tuberculosis makes its appearance are the lungs, the lymphatic glands, 
the bones and joints, the mucous membranes, particularly those of the 
larynx and intestines, the serous membranes, the prostate, testicles, 
ovaries, Fallopian tubes, kidneys, uterus, suprarenal capsules, brain, 
liver, spleen. In some of these situations the lesions are practically 
always secondary, as, for example, in the liver and spleen. In others 



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they are most frequently primary, as in the lungs. The occurrence of 
primary tuberculosis in the internal organs may be difficult to explain. 
It is possible, however, for the bacilli to gain access to the lymphatic or 
blood circulation without causing a lesion at the point of entrance. Their 
deposit in some internal organ then occasions the first or primary focus 
of disease. Thus, primary tuberculosis of the mesenteric glands, of the 
lymphatic glands of the neck, or of the postbronchial glands may occur 
without primary disease of the intestines, of the mouth or skin, or of the 
lungs in the several instances. Similarly, primary tuberculosis of the 
kidney or of the suprarenal capsule may occur without any evidence of 
the point of entrance of the micro-organisms. In some cases, of course, 
the primary lesion may be so small and in such a hidden situation that it 
escapes notice. 

After the discovery of the tubercle bacillus a number of diseases 
not previously recognized as tuberculous became identified as forms of 
this disease. Among these is lupus vulgaris of the skin. The histological 
examination shows numerous tuberculous granulations, sometimes ar- 
ranged in striate fashion along the small blood-vessels of the skin and 
containing epithelioid and lymphoid cells and giant cells. The presence 
of the bacilli and the proved infectiousness of the tissue, with the 
histology, render the nature of this disease certain. The warty forma- 
tions frequently acquired by anatomists at points of injury have like- 
wise been shown to be in many cases due to tuberculous infection. 
Scrofula, which was formerly regarded as a special condition predisposing 
strongly to tuberculosis, is now regarded as actual tuberculosis. The 
scrofulous glands of the neck constitute tuberculous adenitis, the infec- 
tion in many cases gaining access through the mucous membranes of 
the mouth and pharynx or through the skin. Scrofulous rhinitis and 
sinusitis have similarly been shown to be forms of tuberculous disease. 
Many cases of joint disease regarded as scrofulous are likewise dependent 
upon the action of the tubercle bacillus. 

Latent Tuberculosis.- — A tuberculous lesion may become encap- 
sulated and limited in its extent before it has invaded tissues widely, 
and may so remain for years without giving rise to manifest clinical 
symptoms. Subsequently, however, the encapsulating membrane may 
be penetrated and widespread infection, local or general, may occur. 
Such latent tuberculosis is particularly frequent in the postbronchial 
glands. These glands are often found enlarged at autopsies in which no 
tuberculous disease of other organs is found. Injections of emulsions of 
such glands in a notable proportion of cases produce tuberculosis in 
guinea-pigs, and thus it has been determined that the glands in question 
are frequently the seat of latent tuberculous disease. The existence of 
such lesions explains the cases of sudden generalized miliary tuberculosis, 
in which no primary focus of the disease was recognized during life. 
It is perhaps well to emphasize the difference between latent and healed 
tuberculous foci. The former are arrested and surrounded by a limiting 
wall of connective tissue through which it is possible for degenerations 
or inflammations to extend and free the tubercle bacillus, or awaken it 
to activity, while in healed foci it is assumed that all infective agents have 
been destroyed, and the original lesion wholly replaced by fibrous tissue. 



DISEASES DUE TO BACTERIA 



341 



Pathological Physiology. — The effect of tuberculosis upon the gen- 
eral health varies greatly. Undoubtedly the bacillus contains or is capable 
of producing toxic substances that have an effect upon the general organ- 
ism; the nature of these, however, still remains undetermined. The 
tuberculin of Koch, a glycerin extract from cultures of the tubercle bacil- 
lus, produces fever with the general symptoms characteristic of pyrexia 
and local reactive changes in existing tuberculous lesions. Among the 
latter, redness or increased vascularization of the tubercles, and soften- 
ing or necrosis of the cells surrounding the bacilli, are most important. 
The last named change deters the growth and multiplication of the 
bacilli themselves, but at the same time makes their escape from the 
focus of disease more easy and thus exposes the individual to the liability 
of general infection. The active substance contained in tuberculin is 
probably a thermostabile polypeptid that is destroyed by pepsin and 
trypsin, but not by erepsin. It is positively chemotactic for leukocytes. 
It does not act upon the tubercle bacillus directly and is not an anti- 
toxin. The tubercle bacillus seems able also to excrete lipase during 
its vegetative life. In addition to this, the tubercle bacillus in its dead 
state contains some body or bodies capable of influencing the organism, 
as was shown by the experiments of Prudden and Hodenpyl, who 
were able to produce nodular lesions by injecting dead bacilli into the 
circulation of animals. Mention has already been made under Caseation 
of the unsaturated fatty acids of tubercle bacilli in the production of 
necrosis. Such substances are also present in dead bacillary bodies. 
These lesions, of course, are not strictly tuberculous, though they 
possess some elements of the natural tubercle. It is altogether prob- 
able, however, that in addition to the tuberculin of Koch and the 
chemotactic substances contained in the body of the tubercle bacilli, 
there are other poisonous substances produced by the growth and 
multiplication of the bacilli in the tissues, that lead to a general de- 
terioration in the health of victims of this disease. Trudeau, Pear- 
son and Gilliland, and others have been able to immunize animals 
by repeated inoculations with bacilli of lowered virulence. Human 
bacilli if injected into cows will raise their resistance to virulent bovine 
bacilli. A form of immunity called "isopathic" (Behring) is thus pro- 
duced. The sera of such immunized animals is not protective or cura- 
tive to other animals. None of the supposed " antitoxic" sera thus far 
produced has been proved to have antitoxic or immunizing power. 

Tuberculosis is primarily a local process, but influences the general 
organism by its direct effect upon the organic functions of the parts in 
which it is located by the development of these as yet unknown toxic 
substances, and later by the widespread infection of the organism. 
Amyloid disease is a sequel of prolonged tuberculosis. The mechanism 
of defence against tuberculosis is only partly known. In the case of 
local lesions of the lungs or other parts the reaction of the tissues prob- 
ably resulting from the activity of chemotactic substances in the body 
of the bacilli themselves, or of similar substances produced by the 
cellular necrosis, leads to the formation of an embankment of cellular 
or fibrous tissue that serves to hold the disease in check. Subsequently, 
the disease may be wholly eradicated by degenerative changes terminat- 



342 



A TEXT-BOOK OF PATHOLOGY 



ing in calcification. That such favorable results are not uncommon is 
proved by the frequent occurrence at autopsies of small sclerotic or 
calcareous areas in the lungs. Tuberculosis is frequently cured in these 
early stages, but after it has reached the degree of intensity or the wide- 
spread character that makes it recognizable by our present methods of 
physical examination, the reactive processes are usually no longer able 
to cope with its progress. 

The defensive reactions of the blood against the tubercle bacillus 
are not very potent. In the serum there appear agglutinins, opsonins, 
and a complement-fixing body in excess of those found in non-infected 
persons. Use is made of the opsonins in bacterin therapy, as it is possi- 
ble to increase their strength by injection of some of the products of the 
tubercle bacillus or of killed cultures. Repeated injections of the bacilli 
or their products into lower animals have not developed any valuable 
antiserums for therapeutic purposes, but claims have been made that 
acitve immunization with living bacilli will raise the resistance of 
animals and man. Such methods are, to say the least, hazardous. 

Pseudotuberculosis. — This name has been applied to conditions occasionally met 
with in which nodular lesions resembling tubercles, but containing micro-organisms 
of different kinds, have been found in the liver, kidneys, and other organs. Pseudo- 
tuberculosis is not a specific disease, as a number of distinct infections assume this 
pathological character. Among the organisms isolated are various streptothrices 
and acid-proof bacilli resembling the tubercle bacillus to some extent (see below). 
In the lower animals, and very rarely in man, certain animal parasites cause lesions 
of the same kind. 

The Smegma Bacillus. — A bacillus quite closely resembling the tubercle bacillus 
was discovered in the smegma and later on the skin of various parts of the body. 
It not only resembles the tubercle bacillus morphologically, but behaves in a similar 
manner toward stains. In particular this bacillus holds its stain when attempts are 
made to decolorize with acids: The bacillus is frequently found in urine, and thus 
may cause an erroneous diagnosis of tuberculosis of the kidney or bladder. It 
may usually, though not certainly, be distinguished by its easy discolorization with 
absolute alcohol. 

Other Acid-proof Bacilli. — Several other bacilli that are refractory to decoloriza- 
tion with acid or alcohol have been discovered in milk and butter, in sputa, and in 
purulent or gangrenous collections in the lungs and elsewhere. Injections of pure 
cultures of some of these cause fibrinous inflammations in the peritoneum of guinea- 
pigs and rabbits, or pseudotuberculous formations, but not the specific lesions of 
tuberculosis. 

The lesions resulting from inoculation with acid-fast bacilli show a striking re- 
semblance to those of tuberculosis, and only a careful microscopical examination 
serves to distinguish them. Examined with a microscope, the lesions of this spurious 
tuberculosis present a more inflammatory appearance and show a tendency toward 
abscess formation. In very rare instances, however, an approach toward the typical 
histologic conditions of genuine tuberculosis, characterized by the formation of 
giant cells, epithelioid cells, and caseation, is seen in this form of pseudotuberculosis. 

The causative organisms in such infections range in a biological series from short, 
bacillary, rigidly acid-fast forms very like tubercle bacilli to longer threads slightly 
acid fast, to groups of higher bacteria growing in mycelia and not acid fast, related 
to actinomyces and streptothrix. 

The streptothrices may produce infiltrative and proliferative lesions like the 
organisms just discussed. They have been found in various parts of the body as 
the causative factors in abscesses. The lung process is infiltrative, then suppura- 
tive, then necrotizing. Some of the streptothrix infections may resemble pulmonary 
tuberculosis and can be diagnosed only by isolating the organisms or by skin tests. 
It has been found possible to differentiate the various infections with these higher 



DISEASES DUE TO BACTERIA 



343 



bacteria by means of skin tests. Preparations made from cultures of the various 
organisms, tubercle bacilli, partly acid-fast organisms, and those of streptothrix 
type, are rubbed upon an abraded skin surface; a swollen red area will arise in response 
to the preparation made from the causative bacterium and not to others. 

Pneumonomycosis aspergillina. — In man and in animals pulmonary infection with 
forms of aspergillus, especially Aspergillus fumigatus, may occur in a pseudotubercu- 
lous form. The lesions are exudative and proliferative, and central caseation may be 
conspicuous. The fungi which belong to the group of hyphomycetes are readily dis- 
tinguished by the abundant mycelial threads and the conidia. Infection of other 
organs may occur spontaneously or experimentally. 

Pharyngomycosis leptothricia. — The Leptothrix buccalis is a normal inhabitant 
of the mouth, and occasionally produces a pathological lesion of clinical interest. The 
organism probably belongs to the group of pleomorphic bacteria, though its exact 
position is not determined. It consists of fine threads, of wavy or spiral character, 
composed of rod-like segments. Occasionally spore-like bodies are found at the free 
ends of the filaments. The organism sometimes penetrates and multiplies in the 
crypts of the pharynx, causing a chalk-like nodule or deposit. Secondary inflamma- 
tion may be occasioned. (See also Diseases of the Pharynx.) 

FOWL-TUBERCULOSIS 

Tuberculosis in various forms of fowl and birds (avian tuberculosis, tuberculosis 
gallinarum) is a disease similar to, but not identical with, human tuberculosis. The 
spontaneous disease of birds occurs most frequently in the liver, the lungs being never 
primarily involved. In the liver are found nodules composed of a large central ne- 
crotic area sprinkled with chromatin debris surrounded by a zone of large epithelioid 
cells containing numerous nuclei, intermixed with small round cells. Tubercle bacilli 
are present in enormous numbers. The structural and cultural differences of the 
human and avian bacilli have been discussed on page 333. 

Despite the similarity of the bacilli of the human and avian types of tubercle 
bacilli, it does not seem that the latter can produce tuberculosis in man. In the few 
cases in which avian bacilli have been isolated from human lesions, the simultaneous 
presence of human bacilli was not satisfactorily excluded. 

Experimental inoculations of bacilli isolated from the spontaneous disease will 
produce the same disease in birds; but if animals, such as guinea-pigs or dogs, which 
are very susceptible to human tuberculosis, are inoculated, they frequently resist 
infection, though they occasionally succumb to very large doses. In the latter case 
tubercles are usually absent, but large numbers of bacilli are found in the organs and 
in the abscesses which result at the point of inoculation. According to Nocard, rabbits 
show a marked degree of susceptibility to this form of tuberculosis. 

Although there is no doubt that fowl in some instances have become infected 
through human sources, yet experimentally they exhibit a very high degree of resist- 
ance to human bacilli. If, however, the human bacilli are passed through birds for 
three or four generations, or are placed in the peritoneum of fowl in collodion sacs, for 
the same length of time, the virulence to birds is not only heightened, but the bacillus 
changes in its structural and cultural characteristics, assuming those of the bacillus 
isolated from spontaneous avian tuberculosis. The same is true of avian bacilli 
when these are inoculated in animals susceptible to human bacilli. With each passage 
through such an animal the virulence of the bacillus is increased, and the form and 
cultural characteristics become more and more like those of the human bacillus. 
From these experiments it appears that the avian tubercle bacillus is only a modifica- 
tion of the ordinary tubercle bacillus caused by its growth in the tissues of the bird. 

LEPROSY 

Definition. — Leprosy, lepra, or elephantiasis grsecorum, is an 
infectious and mildly contagious disease caused by a specific bacillus, 
the Mycobacterium lepras, discovered by Hansen. 

Etiology. — The essential cause of leprosy is a bacillus which closely 
resembles the tubercle bacillus, though it is less frequently curved and 



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A TEXT-BOOK OF PATHOLOGY 



is somewhat more easily stained. Further, it differs in its grouping 
in the tissues and in its character of growth. The organism is usually 
found in large numbers in the leprous lesions and in the nasal mucus, 
whether there be definite leprous ulcerations in the nose or not. In the 
tissues the bacilli are found within large cells of the specific granulation 
tissue (lepra cells). In the anesthetic form it is found in the nerves 
and central nervous tissues. The organism has been demonstrated in 
the blood in certain cases of the tubercular type. It is readily stained 
by any of the methods applicable for the tubercle bacilli or by Gram's 
method. It frequently shows light areas like those of the tubercle 
bacillus; these have been regarded as spores, but are more probably 
produced by fragmentations, as in the case of the tubercle bacillus. 

Musgrove, Clegg, and Duval have succeeded in cultivating the 
leprosy bacillus upon media containing tryptophan. The organisms 
do not possess the power of digesting the protein molecule to liberate 
this substance, so that it must be introduced artificially or supplied 
to them by means of symbiotically growing amebae or bacteria. Two 
kinds of cultures have been observed, one growing in a luxuriant yellow 
form, the other as a scanty, almost colorless colony. The importance 
of the two is not yet understood. Some believe that the scanty growth 
is the true lepra bacillus. Wolbach and Honeij 's work upon human and 
rat leprosy would suggest that four kinds of organisms — diphtheroids, 
pigmented acid-fasts, non-pigmented acid-fasts, and anaerobes — have 
been cultivated in different parts of the world. It would seem that 
they may all be involved, or that two are present as varying examples 
of one organism. What has been called typical leprosy has been pro- 
duced in rabbits ' eyes, mice, and especially monkeys. Flies of the genera 
Musca and Stomoxys have been accused of carrying lepra bacilli. In 
one case the disease has been given to a condemned criminal by direct 
inoculation. 

Besides the specific bacillus, other conditions are important in the 
etiology. Thus, the disease flourishes in certain localities extensively 
and little in other places. It is uncommon in the United States, but some 
of the Gulf States, particularly Louisiana, have considerable colonies, 
and in the Northwest and on the Pacific Coast it is met with among the 
Norwegian and Chinese immigrants. In Mexico, South America, Nor- 
way and Sweden, India, and other Asiatic countries it is common, and 
the Sandwich Islands are particularly affected. During the Middle 
Ages it flourished in Europe as a universal scourge, unsanitary conditions 
probably acting as the predisposing cause. Certain articles of diet are 
believed to occasion it, particularly fish; this view, however, lacks proof. 

The disease must be regarded as contagious, though less so than 
tuberculosis. Intimate association for a long time seems to be necessary 
for its transference. Insects have been thought to transmit the disease, 
but proof is as yet not forthcoming. It is probably transmitted from 
parent to offspring in rare instances. The bacilli have been found in 
the hyalin substance, the syncytial cells, chorionic villi, and vessel 
walls of the placenta. 

The importance of the nose as a seat from which leprosy bacilli 
are disseminated is emphasized by the facts that the bacilli are present 



DISEASES DUE TO BACTERIA 



345 



here even when no leprous lesions exist, and that ulcers are common on 
the septum. The lesions when present are softer than those on the 
skin and may be found in both the tubercular and anesthetic forms. 

Pathological Anatomy. — Leprosy presents itself in two forms — 
the tubercular and the anesthetic. In the former there are developed 
in the skin of the face, the extensor surfaces of the elbows and knees, 
about the hands, or less frequently elsewhere, small or large nodular 
elevations. These at first are reddish in color, with apparent inflam- 
matory reaction. Later they lose their redness and remain as indolent 
lesions that grow very slowly or remain stationary. They may break 




Fig. 130. — Nodular leprosy (Goldschmidt). 



down, forming ulcerations which do not readily heal, or they may be 
gradually converted into fibrous cicatricial tissue, causing unsightly 
deformities of the skin. The appearance of the patient's face is highly 
characteristic, and is known as leontiasis leprosa (Fig. 130). The mucous 
membranes and some of the internal organs may be involved. The 
anesthetic form is usually marked by less conspicuous lesions, but sub- 
jective symptoms, such as hyperesthesia and neuralgic pains, and 
later ulcerations partly trophic in nature, may make it a more serious 
variety. In the skin there are found whitish or brownish spots, slightly 
if at all elevated or altered in consistency. Later, ulcerations may 



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A TEXT-BOOK OF PATHOLOGY 



appear. Very commonly the anesthetic and tubercular varieties are 
coexistent. 

The chief seats of the leprous nodule are in the corium and sub- 
mucous tissues. It invades, by cellular extension, the adjacent nerves, 
vessels, muscles, and sweat-glands, and may be found in the epithelial 
coverings. 

The nodules occurring in the liver, spleen, and testes in this disease 
are admitted to be similar to the nodules of the skin, those found in the 
lungs, kidneys, and intestines, as well as those of the serous surfaces, 
are believed by many to be tuberculous and the result of secondary 
infection. These two diseases are certainly frequently associated; 
probably 40 per cent, of the cases of lepra become tuberculous. 

Other forms of secondary infection occur. Thus injuries of super- 
ficial lesions may allow pyogenic infection, and extensive ulcerations 
and gangrenous necrosis may ensue. The terms lepra mutilans and 
lepra gangrcenosa are applied to such; and various micrococci and sapro- 
phytic organisms have been discovered in such cases. The histology 
of leprosy is given on p. 154. 

Pathological Physiology. — Infection with the lepra bacillus leads 
to local rather than general disturbances. The toxins of the disease, if 
such there be, are not of great virulence, and constitutional symptoms 
are, therefore, wanting as a rule. In the later stages fever and other 
systemic disorders may be occasioned by secondary infections. A 
supposed antitoxic substance has been prepared and has been largely 
used. It is impossible to claim or disclaim the antitoxic nature of this, 
as no toxins have as yet been isolated or obtained in any form, and 
the supposed antitoxic substances cannot, therefore, be tested. 

In the anesthetic form it was formerly customary to regard the 
pigmented or light-colored spots as a result of trophic disturbance, and 
more destructive lesions, such as ulceration and gangrene, received a 
similar explanation. Recent investigations, however, seem to show 
that in these cases there is usually from the first a leprous change in 
the tissues due probably to thickening of vessel walls, and that sec- 
ondary infections frequently play a part, though trophic disturbances 
must still be admitted to a certain extent. The disfigurements of 
leprosy are partly the result of ulceration and partly due to fibrous 
tissue contraction which acts by cutting off the blood supply and by 
distorting the soft parts; to this must of course be added, as just sug- 
gested, the lack of trophic nervous influence. 

BACTERIUM MUCOSUM CAPSULATUM GROUP 

This is a very large group, chiefly saprophytic, in the intestinal 
tract of men and animals, but includes a few important highly patho- 
genic varieties. They are all Gram-negative, non-motile, blunt-end 
rods, growing luxuriantly on artificial media, and with active ferments 
against carbohydrates. Some possess capsules in the body only, others 
in certain artificial media as well. Perkins divides them into three 
convenient groups: 

(a) The Bacterium aerogenes type ferments all carbohydrates, with 
the formation of gas. 



DISEASES DUE TO BACTERIA 



347 



(b) Bacterium pneumonia? type ferments all except lactose, with gas. 

(c) Bacterium lactis aerogenes ferments all as above, except saccha- 
rose. 

This order represents their frequency and pathogenicity. The 
first class is found in abscess, pneumonias, and inflammations of serous 
membranes. The most important member of the second group is 
commonly called "Friedlander's bacillus," an organism seldom found 
aside from pneumonia. (See Friedlander's Pneumonia, p. 297.) The 
third group contains very few pathogenic varieties, but is most com- 
monly concerned in milk souring. 

The exudates caused by all the pathogenic members of this group 
have one or both of two characters. The exudate may be viscid or 
it may contain swelled up cells in which the organisms lie (Mikulicz 
cells and swollen cells of Friedlander's pneumonia). The bacteria pos- 
sess a mild lytic effect upon epithelium and endothelium. The organ- 
isms give rise to very few antibodies. 

A very important non-pathogenic organism not far removed from 
the third division is the Bacterium bulgaricum of Massol. This breaks 
up the carbohydrates of milk and produces lactic acid. This is recom- 
mended by Metschnikoff as an intestinal antibacterial agent. 

The Bacillus pyocyaneus is a Gram-negative, occasionally pathogenic organism 
found in pus having a bluish or greenish color. The bacillus is small in size, fre- 
quently occurring in chain formation, and is actively motile. 

Upon artificial media it produces colored growths and a soluble pigment, which 
gives to the culture-medium for some distance from the growth a greenish, or in 
some cases a dark blue, coloration. The organism in pure culture is highly virulent, 
producing intense suppurative inflammations. Although found normally in the ex- 
ternal ear, the axilla, the groin and anal region, it can under certain circumstances be 
the cause of boils, subcutaneous abscesses, otitis media, or, when penetration has been 
accomplished, serous surface inflammation may arise and occasional instances of 
general pyocyaneus infection have been observed. The exudates are thin and 
purulent but very frequently bloody or at least blood tinged. 

The organism acts destructively upon other bacteria, so that a fatal dose of 
Bacillus anthracis may be rendered innocuous by the simultaneous injection of 
B. pyocyaneus. The destructive effect has been demonstrated in vitro. It seems 
dependent on ferments as well as intracellular substances contained in the bacillus. 
The toxin is hemolytic and parenchymatous degeneration arises in the liver, kidneys, 
etc. 



Diseases Due to Spirilla 

CHOLERA 

Definition. — Cholera is an acute infectious disease caused by a 
spirillum or vibrio. 

Etiology. — The specific cause of cholera is the Spirillum or Vibrio 
cholera? asiaticaz. This organism is frequently spoken of as the comma 
bacillus of Koch. It is a short rod, from 0.8 to 2 n in length, and usually 
somewhat curved. The term "comma bacillus" is applied to it on 
account of the latter fact. It is found abundantly in the rice-water 
discharges of choleraic patients, and is not rarely arranged in threads, 
though vibriones are not actually attached to one another (Fig. 131). 



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A TEXT-BOOK OF PATHOLOGY 



It is motile, the motility being due to a single flagellum attached at one 
end. In artificial cultures the organisms are actually joined to form 
spirals of greater or less length, and these may present a rapid rotary 
movement. 

The demonstration of the cholera spirillum is usually easy, as ordi- 
nary stains color it intensely. It is Gram-negative. Even the flagel- 
lum may be stained by the ordinary stains, though more definitely 
shown by special methods. 

The cultivation of the spirillum is usually easy. Cultures may be 
obtained upon agar-agar, blood-serum, or other media, but the gelatin- 
culture is most characteristic. In puncture-cultures the growth occurs 
along the entire length of the puncture, but particularly at the top, 
where the supply of oxygen is abundant; and the gelatin becomes lique- 




Fig. 131. — Spirillum of Asiatic cholera, from a bouillon-culture three weeks old, showing 
numbers of long spirals; X 1000 (Frankel and Pfeiffer). 



fled. This gives rise to a peculiar nail-shaped or funnel-shaped forma- 
tion. In plate-cultures the growths first appear in the lower strata 
of the gelatin as small granular whitish spots which extend toward 
the surface, liquefy the gelatin, and thus produce excavations. The 
appearance to the naked eye suggests small air-bubbles in the media. 
Under low powers of the microscope the culture is seen to be coarsely 
granular, the size of the granules varying with the age of the culture. 
The bottom of the .growth presents an appearance like that of a surface 
sprinkled with powdered glass. 

When grown in bouillon or other liquid media the cholera microbe 
produces nitrites and indol so abundantly that the addition of a little 
pure sulphuric acid or hydrochloric acid (without nitrite solution) leads 
to a reddish coloration — "cholera-red." The indol reaction is not abso- 
lutely diagnostic, since other spirilla may cause it. Negatively, however, 
the test is extremely useful, since its absence excludes the cholera germ. 
A definite quantity of peptone is necessary to make the test reliable. 



DISEASES DUE TO BACTERIA 



349 



Therefore, instead of bouillon an alkaline 1 per cent, peptone solution 
containing 0.5 per cent, of sodium chlorid is preferable (Dunham). 

The cultures of cholera grow best at a temperature about that of 
the body, but they may thrive at much lower degrees of heat. Exposure 
to a temperature of 52° C. (125.6° F.) for four minutes may cause their 
destruction, but ten or fifteen minutes' exposure at 55° C. (130° F.) does 
not always prove destructive. They may thrive in distilled water or in 
water containing saline matter; in or upon various forms of food; upon 
clothing, and the like. 

Distribution. — The cholera spirillum is found in the intestinal con- 
tents and mucosa. The organism is not found in the blood nor in any 
organ or tissue except the gastro-intestinal tract. 

The pathogenicity of the cholera spirillum is now admitted uni- 
versally. Injected into the peritoneum of animals it causes a rapid 
fall of temperature, abdominal tenderness, and collapse. The perito- 
neum shows signs of beginning inflammation, and the organisms are 
found in abundance within the cavity. It has been possible also to pro- 
duce intestinal changes almost if not identical with those of human 
cholera in animals by arresting the peristalsis of the intestines with 
injections of opium, rendering the liquids of the stomach alkaline with 
sodium carbonate, and then feeding cultures. In man a few auto- 
infections have occurred, the experimenter swallowing cholera cultures. 

Other Causes Operating in Cholera. — Infected water is the chief 
source of transmission of cholera. The microbe may live in water for 
months. It is said that the Ganges River contains the spirilla constantly. 
Certain climatic conditions favor the development of the disease. Thus 
it is constant in certain regions of India, and spreads thence when the con- 
ditions become favorable. The evidence shows that the germ is carried 
by individuals, or by infected food and the like. The disease flourishes 
in warm seasons of the year, and an epidemic is usually brought to a 
close by winter frosts. 

Individual disposition plays a part in the occurrence of the dis- 
ease, for the germ is easily destroyed by the acid gastric secretions, 
and infection is, therefore, most likely to occur when gastro-intestinal 
deragenments furnish a favorable predisposition. 

Pathological Anatomy. — The lesions of this disease are found 
in the intestinal tract, and will be described in the appropriate 
section. 

Secondary lesions of other organs are the result of desiccation plus 
the action of toxin and are seen in the parenchymatous organs as fatty 
degeneration, on the serous surfaces as light fibrinous deposits, on mucous 
surfaces as congestive catarrhal lesions and in the tissues generally as 
marked congestion. 

Pathological Physiology. — A number of toxins have been isolated 
from the blood of cholera patients and from cultures. The exact nature 
of these and the relations of the several forms remain to be determined. 
It is certain, however, that toxins produced in the intestinal tract give 
rise to many of the symptoms of the disease. Injection of the filtrate 
of cultures causes collapse and other symptoms like those of the algid 
stage of the disease. The principal toxic substance seems to be closely 



350 



A TEXT-BOOK OF PATHOLOGY 



attached to the organism itself (endotoxin), but a secreted extracellular 
toxin may also be found in the culture fluid when the organisms are 
enclosed in a collodion sac. The human or animal organism in some 
way develops immunizing or protective substances in the course of 
infection, and it has been found possible by a process of vaccination 
with cultures of gradually increasing virulence to protect animals and 
human beings from the disease. Haffkine's protective vaccination 
of human beings yielded very encouraging results. He at first used 
an attenuated culture and then one of high virulence. The injections 
are made under the skin, where the spirilla soon die, but their bodies 
set up the antibodies. He inoculated 200,000 persons in India. Pfeiffer 
found that the serum of animals so vaccinated had a distinct action 
upon cholera spirilla, causing their agglutination or destruction, and 
possibly in this way exercising a protective influence. These antibodies 
may be used to diagnose a case of cholera, either by agglutination, 
like the typhoid Widal test, or by the Pfeiffer intraperitoneal test. 

The rapid and copious intestinal discharges of cholera lead to con- 
siderable inspissation of the blood, and, as the organism seems to attract 
alkali, there is produced a condition of acidosis upon which the comatose 
state of severe cases depends. Examination of the blood during the 
height of the malady may show greatly increased numbers of the red 
blood corpuscles. 

Organisms Resembling the Cholera Vibrio 

Spirillum of Finkler and Prior. — This organism was discovered by 
the investigators, whose names it bears, in the stools of a case of cholera 
nostras. It resembles the vibrio of Asiatic cholera in its shape and 
somewhat in its manner of growth and its production of the indol reac- 
tion. It differs, however, in being somewhat longer and more slender 
and in coagulating milk when this is used as the culture-medium. 
The growth upon gelatin is more rapid, so that within twenty-four hours 
in the case of a puncture-culture the liquefaction has proceeded so far 
along the puncture that an elongated sac-like excavation is formed, in 
which turbid liquid is contained. It has not yet been proved that this 
organism has an etiological relation to cholera nostras; its pathogenicity 
is improbable. 

Spirillum tyrogenicum is an organism discovered in old cheese by 
Denecke. It resembles the last-named variety very closely, and differs 
from the vibrio of cholera in liquefying gelatin quickly, though the 
rapidity is not so great as in the case of the Finkler and Prior organism. 

Spirillum Metschnikovii. — This organism was discovered by Gama- 
leia in the intestines of chickens affected with choleriform disease. It is 
somewhat shorter and thicker than the cholera spirillum. In culture it 
resembles the vibrio of cholera very closely, though the trained bacte- 
riologist can easily distinguish them. The organism is non-pathogenic 
for man, but chickens, pigeons, and guinea-pigs are highly susceptible. 

Besides these spirilla or vibriones which have been discovered in 
various diseases, a number of organisms that resemble closely the 
spirillum of cholera have been found in the water of streams supplying 
the drinking-water of cities. Among these Neisser described the Spirit- 



DISEASES DUE TO BACTERIA 



351 



lum berolinense, obtained from the water of the Spree in 1893. Dunbar 
and Oergel isolated a similar organism from the water of the Elbe, 
and a number of others of like character are known. The relations, 
however, of the different forms to each other and the differentiation of 
these varieties have not as yet been definitely determined. 

Pathogenicity. — Some of the forms described produce violent 
gastro-intestinal disturbance and death in a certain proportion of ani- 
mals prepared by injection of opium and alkalinization of the intestinal 
tract with soda and then fed with pure cultures of the organisms. They 
are evidently highly irritating bacteria, and some remote relationship 
seems to exist between them. This, however, cannot be positively 
asserted. 

The separation of these forms from the true cholera spirillum is by 
no means easy. It is best done by the agglutination and bacteriolytic 
tests. For this purpose it is necessary to have the serum of an animal 
immunized against the cholera germ, and to this only the cholera spiril- 
lum will react. 



Definition. — Syphilis is a specific contagious disease of man, believed 
to be caused by the Spirochceta pallida or Treponema pallidum. The 
disease does not occur spontaneously in any of the lower animals. 



Fig. 132. — Spirochseta pallida from chancre, stained by Levaditi's method; X 1500 
(Bulletin No. 1, Medical Department, IT. S. Army, 1913). 

Etiology. — Many organisms have been describe d for this disease, 
the most discussed being Lustgarten's bacillus and Schaudinn's spiro- 
chete. The former is a large rod, said to lie in and between the cells 
of lesions of general tubercle-bacillus-like morphology. It has not been 
cultivated. It has now been given up as the cause of syphilis. 

In 1905 Schaudinn discovered an organism in syphilitic lesions 
which he named Spirochceta pallida. Later during the same year and 



Diseases Due to Spirochetes 



syphilis 




352 



A TEXT-BOOK OF PATHOLOGY 



with the co-operation of Hoffman he was able to demonstrate the organ- 
ism in every case of uncomplicated syphilitic disease examined by him. 
The spirochete is described by Schaudinn (Fig. 132), as an extremely 
delicate, actively motile, faintly refractive, spiral, long, thread-like or- 
ganism, tapering at both extremities and terminating in pointed ends. 
It propels itself during life by rotating around its longitudinal axis, 
first in one direction and then in another. In the resting state undu- 
lating movements may be observed passing along the length of the 
organism, suggestive of an undulating membrane. In addition, bend- 
ing, twisting, twining, and whipping movements of the whole body may 
be noticed. The organism varies from 4 to 14 /x in length, ranging in 
thickness from a size too minute for measurement to 0 . 25 /z in the largest 
specimens. The spirals range from six to fourteen in number ; they are regu- 
lar, narrow and deep, corkscrew-like, and appear constantly so, no matter 
whether the specimen be derived from initial lesions, papules, lymphatic 
glands, spleen, etc., or from the scleroses of apes. The curves are large 
arcs of a small circle, while other spirochetes occurring with the pallida 
show smaller arcs of a large circle. By means of Lofner's method 
of staining flagella a long delicate flagellum has been noted at each 
end of the organism; in some specimens two flagella at one end were 
seen, giving the appearance of an attempt at longitudinal division. 
Novy could find no evidence whatever of longitudinal division. Schau- 
dinn has failed to discover any signs of an undulating membrane or a 
nucleus in the stained specimens, though the latter has been reported 
by Wechselmann and Loewenthal in specimens examined with the aid of 
the ultramicroscope. At present there is some difficulty in distinguishing 
positively between the Spirochceta pallida and some common non-patho- 
genic forms. Too much weight cannot, therefore, be given to the dis- 
covery of spiral organisms unless the investigator has had considerable 
experience. 

The Spirochaita pallida has been found in the initial lesions, the 
secondary papules, the enlarged lymphatic glands, the mucous patches, 
the secretions, blood, and lately, by Noguchi, in the late nervous manifes- 
tation, paresis. 

The most conservative authorities now accept this as the cause 
of syphilis. As will be seen below practically all of Koch's postulates 
have been fulfilled. 

Schaudinn maintained that the spirochetes are animal organ- 
isms belonging to the group of flagellates and proposed the name 
Treponema pallidum. The researches of Novy seem to be conclusive 
that this is not the case. He could find no evidence of an undulat- 
ing membrane, nucleus, or longitudinal division, and, on the contrary, 
only the transverse fission characteristic of bacteria. 

Wherever later studies place this spiral organism, certain characters 
have been made known by recent work suggesting its bacterial nature. 
It has now been cultivated by many persons after a technic elabor- 
ated by Noguchi. It grows anaerobically in colonies resembling those 
of bacteria and indicates its essential parasitic nature by requiring 
in this anaerobic culture fresh animal tissue. It does not require any 
intermediate stage to be infective, for, as we shall see, infection usually 



DISEASES DUE TO BACTERIA 



353 



arises by direct contact, and, as the work of Noguchi has also shown, 
it will, cause syphilitic lesions in rabbits' testes by inoculation of cultures 
or of fresh material from human lesions. Syphilis can be produced in 
the anthropoid apes by inoculation of fresh human material or cul- 
tures upon the skin, and a skin affection will result from the same 
treatment in the lower monkeys. When animals are infected with 
syphilis by experimental methods, the spirochete can be recultivated 
from their lesions. The cultures at hand develop a protein-like body 
which has some relation to the infection, because when a sterile solution 
thereof is applied to an abraded skin area an inflammatory papule 
results. This is the so-called "leutin reaction," and it has been used 
as a diagnostic test. The results of this and the Wassermann or 
complement-fixation test (q. v.) indicate the active antibody forma- 
tion on the part of the body. Agglutinins are also formed. All of 
these recently discovered features favor a classification among the 
spirochetes. 

Whatever the nature of the organism, it is quite certain that the 
disease is definitely infective. In the great majority of cases infection 
occurs by direct inoculation in sexual intercourse. It may, however, 
be conveyed in many other ways. Physicians are sometimes infected 
in performing surgical operations or in examining syphilitic cases; 
persons have frequently been inoculated in the process of tattooing or 
vaccination when saliva or vaccine-lymph from diseased individuals was 
employed. Infection may be caused by kissing, or indirectly by the use 
of drinking-vessels which have been employed by the diseased. The 
newborn may be syphilitic in consequence of disease of the father or 
mother; and healthy wet-nurses may be infected by syphilitic nurslings. 
In addition to the specific cause, surrounding conditions and individual 
susceptibility doubtless play a part. During the Middle Ages this dis- 
ease at times and in certain places almost attained the character of a 
universal scourge. Its manifestations were severe, its course rapid, and 
in every sense its nature was malignant. Cases of this description are 
exceedingly rare at the present day. 

Pathological Anatomy. — The pathological course of this disease 
may be divided into three stages : the initial, the secondary, and the tertiary. 
The disease may abort at any stage, but such an occurrence is rare. 
Not infrequently, especially in women, the first and even the second 
stage as well may be overlooked. 

Chancre. — -In the initial stage there is formed at the point of inocu- 
lation a primary lesion, commonly termed " chancre." This may make 
its appearance first as a somewhat red and inflamed papule, or as a 
vesicle which ruptures and thus produces an erosion. When it begins 
as a papule the surface soon becomes eroded, and thus a superficial 
ulceration is established. The peculiar feature of this lesion, to which 
Hunter called particular attention, is its hardness or induration, and it 
is by this feature largely that it is distinguished from the soft chancre 
or chancroid. The initial or primary lesion may remain indolent or as a 
small erosion for a long time, or it may soon cicatrize and leave a more 
or less definite scar. The chancre occurs upon the gans penis or prepuce, 
or within the urethra of the male; and in the vagina, urethra, or upon 

23 



354 



A TEXT-BOOK OF PATHOLOGY 



the cervix uteri and external genitalia of the female. Extragenital 
chancres may be observed in the rectum or anus, on the lips or tongue, 
tonsils or pharynx, the fingers, or other parts. 

Secondary Lesions. — At the end of a variable period of time after 
the eruption of the initial sore secondary manifestations of the disease 
make their appearance. The spread at first follows the lymph-channels, 
but when once the infiltrative lesion of the blood-vessels begin, as in late 
primary syphilis, the dissemination is by the blood-stream. This ini- 
tiates what has been called constitutional syphilis, an appellation not 
at all inappropriate since there is usually some evidence of a general 
infection, at least in virulent infections. For example there may be 
slight fever and headache, with a blood count showing anemia and an excess 
of mononuclears; severe typhoid like septicemic states are known. The 
first secondary lesions, as a rule, are swelling and induration of the neigh- 
boring lymphatic glands {syphilitic bubo), a lesion that does not tend to 
suppurate thus differing from chancroidal bubo. Later the superficial 
lymph-glands of the entire body become swollen and, like those in the 
neighborhood of the lesion, indurated. At the same time eruptions 
upon the skin and mucous membranes make their appearance. The inter- 
val between the primary and the secondary manifestations is variable. 
Sometimes it is but a few weeks (three or four), at other times it may be 
several months. Among the lesions of the skin various forms of papules, 
macules, and scaly eruptions are most frequent and characteristic, but 
it is impracticable to describe them all since any eruption known to the 
skin seems at times to have a syphilitic origin. The lesions are usually 
symmetrically arranged on the two sides of the body and cause but little 
irritation. Their color has been called coppery and it is rather the rule 
for such a discolored spot to remain after an eruption has healed; at 
times, however, an area devoid of cutaneous pigment results. Perhaps 
one of the most characteristic points about syphilitic skin lesions is their 
tendency to heal in the center while spreading out in an annular form. 
On the mucous membranes and neighboring skin the most characteristic 
lesion of this stage is the condyloma latum, or mucous patch. This appears 
as a somewhat elevated patch with superficial erosion or ulceration. The 
surface has a necrotic appearance and may be covered with more or less 
secretion. 

Tertiary Lesions. — These may take the form of ordinary inflam- 
matory changes of the mucous membranes or of other parts, with a 
pronounced tendency to fibrous-tissue overgrowth and thickening, or 
of definite nodules — the syphilitic gummata, or syphilomata. Among 
the diffuse syphilitic changes of the tertiary stage may be ranked 
nodular thickening of the intima of the blood-vessels, certain changes 
in the liver, spleen, kidneys, and heart muscle, and also similar altera- 
tions in the nervous system. The gross alterations of specific cirrhoses 
depend upon what has been called syphilitic granulation tissue, a form 
similar to that seen in chronic tuberculosis but differentiated by the pre- 
ponderance of perivascular round cell infiltration and the paucity of 
giant cells. It would seem, too, that the arrangement of fibres and new 
capillaries is distinctly more disorderly. These points, however, do not 



DISEASES DUE TO BACTERIA 



355 



always hold so that the discovery of the respective micro-organisms is the 
only reliable criterion. 

The localized lesions of the tertiary stage — the gummata — are 
most frequent in the bones (tibia, sternum, and skull) ; and in the in- 
ternal organs, such as the liver, lungs, kidneys, heart and brain. 

The gumma presents itself as a nodular mass, varying in size from 
small tubercle-like formations (miliary gummata) to tumors the size 
of an orange or larger (Fig. 133). It is hard, and has frequently an 
elastic character, which has suggested the name "gummy tumor" or 
"gumma." On section, the substance is frequently found to be gelatin- 
ous or mucoid in appearance; but there is nearly always considerable 
induration, either peripheral, in the form of a capsular enclosure, or 




Fig. 133. — Gummata of the liver. 

striate, in the form of bands extending from the center to the periphery 
and into the surrounding tissue. Occasionally gummata soften very 
rapidly and become converted more or less completely into puriform 
collections. When situated in the mucous membranes or adjacent to the 
surfaces of the body, suppurative, fatty, or necrotic softening may lead 
to the formation of superficial ulcerations. These may remain indolent 
or may gradually become cicatrized. Sometimes a gummatous lesion 
disappears entirely by absorption without leaving a trace of its ex- 
istence. 

The histology of syphilis is given on p. 152, among the specific 
infections, so that it is only necessary here to review the general features 
of the pathologic anatomy. The primary effect of the invasion of 
the spirochete is to injure the cells and incite round, and tissue-cell 
proliferation, followed by fluid and connect ve-tissue cell increase. 
The blood-vesseh are attacked early and the spirochete characteristically 
excites endothelioid increase in all of the coats. The intimal changes are 
obstructive, leading to anemia and connective tissue replacement both 
in the vessel itself and the tissues supplied by it. The central necrosis 
of gumma is doubtless due to this. The fibrosis is largely due to the 
prolonged irritative effect of the spirals and to the debris of cellular 



356 



A TEXT-BOOK OF PATHOLOGY 



destruction. Scars of considerable size are formed in the liver, brain, 
kidneys, etc., by the excessive scar tissue. The spirochetes seem to 
prefer those places where blood-supply and cellular activity are greatest, 
such as the bone-forming layer of the periosteum and epiphysis and the 
sinusoids of the liver. Amyloid disease is frequently seen as the result 
of syphilis. 

Parasyphilis is a name given by Fournier to certain diseases, chiefly 
of the nervous system, in the clinical history of which syphilis is practi- 
cally always noted. The pathological lesions are similar but not identi- 
cal with those of syphilis, and some have doubted their luetic nature. 
Noguchi has lately found the Spirochceta pallida in the brain of paresis, 
a discovery which leaves hardly any doubt as to the syphilitic nature 
of this condition. He has, moreover, produced lesions in rabbits by in- 
jecting the brain of paretics. 

Pathological Physiology. — Syphilis is one of the most persistent 
of the infectious diseases, and occasions widespread changes that are 
doubtless toxic in character. The nature of the toxic principles, how- 
ever, is entirely unknown. In the tertiary stage pronounced anemia 
(cachexia) is frequent; and in the secondary stage rapid chloro-anemia 
with leukocytosis is quite common. 



Congenital Syphilis 

Syphilitic lesions may be found in the newborn or may develop 
some time after birth. Obviously this arises from an already infected 
mother, one infected during pregnancy or from the spermatozoon. 
Concerning the last possibility it is generally thought that the spirochete 
is not within the spermatozoon but, carried in with the semen, infects the 
primary blastoderm or the uterine wall. Where the infection comes from 
the mother no matter when infected, the spirochetes pass through the 
placenta into fetal blood; lesions of syphilis occurring in the afterbirth will 
of course increase the probability of fetal infection. When the fetal 
infection is severe, death and maceration may occur in ulero. 

The manifestations of congenital sypnilis are often quite marked upon 
the skin in the shape of erythematous, vesicular or bullous eruptions on the 
hands and feet. Internally one finds sclerotic hypertrophic deformity 
of the liver and spleen, a pneumonic infiltration of a pale color, hyper- 
plasia of the lymph nodes and a certain condition of the bones which is 
quite characteristic. The latter consists of a hyperplasia of connective 
tissue and fatty degeneration at the junction of the epiphyses of the long 
— ^„ bones with the shafts. The blood may 

~ „ present considerable excess in the number 

^tf^SSK^S^^^^' °f mononuclear leukocytes. An almost dis- 
^^IL^ <^Mjw tinctive condition of second dentition is 

Fig. 134.-Hutchinson's teeth. that kn0Wn aS Hutchinson's teeth. This 

consists of a notched indentation of the 
cutting surface of the upper central incisors. In addition, the teeth 
are often wedge shaped and peg-like (Fig. 134). All cases of inherited 
syphilis do not present this condition, and it occasionally occurs in 
non-syphilitic children 



DISEASES DUE TO BACTERIA 



357 



RELAPSING FEVER 

Definition. — Relapsing fever, or typhus recurrens, is an infectious 
disease caused by a specific organism which is found in the blood. 

There are four varieties, depending upon the biology of the spiro- 
chete concerned, but differing very little clinically: 

European relapsing fever, Spirochceta obermeieri; African relapsing 
fever, Spirochceta duttoni, transmitted by the tick Ornithodorus mou- 
bata; American relapsing fever, Spirochceta novyi; Bombay relapsing 
fever, Spirochceta carteri. 

The transmission of the first, third, and fourth is not known, but is 
probably due to some tick or louse. Nicolle 's result would indicate that 
the human form may be transmitted mechanically by the louse, not by 
the biting of this parasite, but scratching into small skin wounds the spirals 
contained in the louse's body and freed when the parasite is crushed. 
Spirochceta obermeieri is described as the type. Opinion is still divided 
as to the proper classification. 

Etiology. — The Spirochceta obermeieri is a flexible spiral organism 
with six to twenty curves, in length several times the width of the red 
corpuscle (7 to 19 ju). It is found in the fresh 
blood, and presents active corkscrew, ser- 
pentine, and vibratory movements due to 
rotation and a flagellum-like extremity (Fig. 
135). Recently it has been claimed by 
Schaudinn that this and other spirochetes 
belong to the group of flagellates (animal 
parasites) and are closely related to the 
trypanosomes. Novy's investigations appear 
to have completely disproved this view. „ _ _ 
The organism stains well with ordinary anilin ^ 135 g 
dyes, but not by Gram's. The relation of mei £j "n^'biood* °(von 
this spirillum to the disease can hardly be Jaksch). 
questioned, as it is invariably present and 

appears in the blood during the paroxysms of fever and disappears 
in the intervals, thus showing its relation to the symptoms of] the 
disease. In the case of Spirillum duttoni the female tick bites, 
becomes infective in a week, remains so all its life, and transmits 
the virus to the young. The spirals are excreted with the feces, which 
are deposited at the end of biting, and rubbed in by the person. All 
forms have now been cultivated by Noguchi in anaerobic cultures of 
defibrinated patient's blood in ascitic fluid agar to which fresh tissue has 
been added. They breed true to type. The spirochetes may be trans- 
formed to mice and monkeys. They are numerous in the blood during 
the fever, but rapidly disappear at the crises, due to the presence of 
a spirochetolytic substance in the blood. Immune bodies also appear 
and can be used to impart passive immunity to other animals. 

Pathological Anatomy. — The spleen becomes greatly enlarged; it 
frequently presents a variegated appearance on section, due to areas .of 
anemic infarction and necrosis, or fatty degeneration alternating with 
deeply congested portions. The spirochetes can be found in this organ, 




358 



A TEXT-BOOK OF PATHOLOGY 



particularly in cells. The lymphatic tissues are swollen throughout 
the body. 

Pathological Physiology. — The peculiar feature of relapsing fever, 
the one that has given it its name, is the recurring paroxysms of 
fever. The cause of this periodicity is as yet unknown, though it is 
likely that the development of the spirochete is such as to determine 
the relapses. 

VINCENT'S ANGINA 

This is an acute infectious, pseudomembranous and ulcerative form of 
pharyngitis and tonsillitis giving a grayish or greenish exudate. The 
process below the membrane is usually necrotizing and spreading, and 
may persist for a long time. There are constitutional symptoms and 
involvement of the regional lymph-glands. The organism of the dis- 
ease is found in two forms, the Bacillus fusiformis and the Spirillum 




Fig. 136.— The fusiform rods and spirilla of Vincent's angina. Smear direct from throat. 

vincenti. They are believed to be two forms of the same organism, as 
the spiral has been said to grow from the rod. The rod is irregularly 
staining and pointed, 3 to 12 fx long by 0.3 to 0.8 /x wide. The spiral 
is long, wavy, uniformly staining, flexible, and has pointed ends. The 
rod forms spores. The organisms are anaerobic, growing best upon 
ascitic fluid agar, on which they appear as minute gray colonies. Gas 
is formed in glucose media. Cultures have a fetid odor. The patho- 
genesis of the organism for lower animals is practically nil; no immunity 
reactions are known (Fig. 136). 

FRAMBESIA OR YAWS 

This is a tropical disease resembling syphilis in its primary indurated 
sore and secondary rash, caused by a spirochete (Spirochceta pertenue 



DISEASES DUE TO BACTERIA 



359 



Castellani) , similar to the Spirochceta pallida. The eruption is yellow- 
ish, papular, covered with crusts, and consists histologically of epi- 
thelial hyperplasia, in the form of papillomatous growths or extensions 
downward, associated with increase of leukocytes, plasma, and eosino- 
phile cells. The disease tends toward recovery, except in children and 
debilitated persons. The productive character of the lesions is not so 
marked as in lues. The disease has been transmitted to monkeys. 

WEIL'S DISEASE 

The syndrome — jaundice, purpura, hemorrhages, albuminuria and 
fever — has within recent years been ascribed to spirochetes residing in the 
blood, liver and kidneys. The organism has been called Sp. 
nodosa — the older name given by Huebener — and Sp. icterohemor- 
rhagica, Inada. Observations in various countries all over the world 
strongly suggest that several varieties of rats harbor the parasite and 
are of importance in transmitting the disease. The spirochete is usually 
quite small, 3-5 n, but may attain a very much greater length. It will 
grow under anaerobic conditions. Guinea-pigs can be infected with human 
blood during the first week of the disease, or with blood of infected rats. 
The spirals are copiously excreted by the kidneys and the urine seems 
to be infective for guinea-pigs for a much longer time than the blood is. 
During a favorably progressing attack^ spirocheticidal substances appear 
in the blood. The pathology of the disease is principally represented by 
an enlarged, fatty liver with stasis in the biliary channels, pigmentation, 
and interstitial leukocytic infiltration; varying degrees of liver cell 
necrosis are seen. In addition one usually finds hemorrhages under the 
skin, mucous and serous membranes and in the kidney, in which last organ 
marked diffuse acute nephritis may be found. 

RAT BITE FEVER 

The bites of rats are at times followed by a tender swelling at the bitten 
place, fever, headache and swelling of the lymph nodes. The first out- 
break lasts 5-7 days, regresses only to reappear after three days. This 
disease is apparently due to spirochetes, of which two varieties have 
been . described — Sp. morsus muris and Sp. muris ratti, organisms 
resembling but somewhat grosser than the Sp. pallida. They can be 
found in the blood, in the bitten area and in the enlarged glands. 

Diseases Due to Higher Bacteria 
actinomycosis 

Definition. — Actinomycosis is a chronic infectious process char- 
acterized by inflammatory reaction of the tissues with a tendency to 
the formation of suppurative foci, and due to the specific action of a 
micro-organism, the Actinomyces bovis. 

Etiology.— Actinomycosis is a disease of cattle, horses, swine, 
sheep, the llama, the elephant, deer, dog, and occasionally of man. 

The specific cause of the disease is an organism which occurs in 
the tissues in the form of clusters having a radiate structure, and it has, 



360 A TEXT-BOOK OF PATHOLOGY 

therefore, been termed the "ray fungus." These clusters may be so 
small as to be invisible to the naked eye, or they may reach considerable 
dimensions by their growth and aggregation. The central part of the 
cluster frequently has a granular appearance, suggesting a mass of micro- 
cocci. Reaching out from this may be seen more or less regularly diverg- 
ing striae or rays, and the periphery is composed of what appear to be 
bulbous extremities of the rays (Fig. 137). 

Cultivation of the Organism. — It was at first thought that there were 
several varieties of this organism but it is now generally accepted that 
there is but one anaerobic ray fungus. Growths have been obtained 

upon sugar-agar, in bouillon, and 
various other media. Suspension cul- 
tures in dextrose agar show in the 
course of two to four days scattered 
colonies in the depth of the agar 
and a shallow zone of closely set 
colonies giving the appearance of a 
dense cloudiness in the medium, 
about 2 to 4 mm. wide, generally found 
at a point about 5 to 10 mm. below the 
surface. It is necessary to incubate 
cultures at 37° C. and to keep the 
incubator steady. 

The growths are essentially anaer- 
obic, and grow best at body tem- 
perature. Under the microscope the 
smaller colonies are found to be 
spherical masses of branching filaments radiating from the center. 
The branching is true branching and increases as the colony grows 
older. 

In bouillon, solid white masses form at the bottom of the tube; none 
appear near the surface. Such development occurs both under aerobic 
and anaerobic conditions, but in the case of the former Wright suggests 
that on account of the compactness of the masses there are really anaerobic 
conditions within the colony. 

The cultivation of these organisms presents unusual difficulties, owing 
chiefly to the frequent presence of other bacteria in the lesions, which 
usually grow more rapidly and more luxuriantly than does the specific 
organism. In a few cases pure cultures are obtained by planting the 
granules directly in bouillon. In some instances of contamination, by 
allowing the tube to stand for several days, the contaminating organisms 
die out and transplants then yield pure cultures. It is killed by exposure 
to a temperature of from 60° to 64° C. (140°-147.2° F.) for ten minutes. 
The micro-organism stains well by Gram's method, the clubs losing the 
stain and taking the contrast stain; it is not acid fast to Gabbet's decolor- 
izing solution after staining with carbol-fuchsin. 

The filaments of colonies immersed in animal fluids, such as blood- 
serum and serous pleuritic fluid, may under certain unknown conditions 
become invested with a' layer of hyaline eosin-staining material of vary- 
ing thickness and the filament may then disappear. Thus structures 




Fig. 137.— Actinomyces cluster (Karg 
and Schmorl.) 



DISEASES DUE TO BACTERIA 



361 



are produced that seem to be identical with the characteristic " clubs" 
of actinomyces colonies in the lesions. 

Pathogenicity. — Inoculation experiments on animals with cultures 
of the micro-organism result in producing in the tissues of the inocu- 
lated animal characteristic " club "-bearing colonies. This club forma- 
tion Wright is inclined to believe represents a kind of protective 
membrane for the mass of the colony against the destructive action 
of the juices and cells of the tissue. After the inoculation of animals 
nodular lesions and in some instances relatively extensive masses were 
produced. They, however, showed little tendency to progress and only 
in a few cases did multiplication of the organism in the body of the 
animal seem probable. In other words, these results simulate closely 
the negative or ambiguous results obtained by other observers who 
inoculated animals with the lesions of actinomycosis. 

The manner of infection with the actinomyces is not completely 
determined. Formerly it was thought that the parasite was carried to 
the tissues by various vegetable substances, particularly the spears of 
the oat-seed and other grains; sometimes these have been found embedded 
in the lesions; in other cases splinters of wood have been discovered. The 
fact that the organism prefers anaerobiosis and grows only at body 
temperature tends to disprove this view, and it is likely that the actino- 
myces is a normal inhabitant of the mouth and gastro-intestinal tract of 
lower animals and always derived from these sources, although, of 
course, infection by infected grain or communication with infected 
animals or persons can transmit the disease. Carious teeth and lesions 
of the mucous membranes may play a part in the etiology. 

Pathological Anatomy. — The pathological changes induced by 
the actinomyces consist of round-celled infiltration and proliferative 
changes in the connective tissue surrounding the parasite, and some- 
times secondary softening, necrosis, or suppuration. The granulation 
tissue of actinomycosis is especially rich in leukocytes, and not infre- 
quently these form dense foci, which later develop purulent collections. 
In cattle the disease affects the lower jaw, less frequently the upper jaw 
or other bones; the tissues of the neck, the tongue, and other parts. 
In man it is met with in the gums, the cheeks, and floor of the mouth; 
in the lungs, intestines, and other internal organs. The naked-eye 
appearance of the lesions may first be simply that of a hard red papular 
formation, with more or less induration surrounding it; later this tends 
to increase in size and may break down, forming necrotic or suppurative 
excavations. The process of repair or cicatrization may proceed in 
some parts to the extent of almost complete repair, while the suppura- 
tive or necrotic change advances in other directions, and thus cavities 
and irregular communicating sinuses are established. The part in which 
the disease exists may be considerably disfigured and much enlarged. 
The pus or necrotic material within the lesions contains peculiar granular 
bodies, the "sulphur granules" or actinomycosis bodies. The sand-like or 
sulphur granules measure 0.2 to 0.6 to at times 1.2 mm. They are of a 
gray, yellow, green, to red color; when young, soft; when older, much 
tougher in consistency. Occasionally calcification of the diseased area 
may take place. When the jaw-bone is affected the disease, as a rule, 



362 A TEXT-BOOK OF PATHOLOGY 

begins about carious teeth, fistulse communicating with the roots of teeth 
(Fig. 138). 

In the case of disease of the lungs some have observed a preliminary 
catarrhal inflammation of the bronchi. More frequently, however, 
there are from the first nodular areas of bronchopneumonia, which 




Fig. 138. — Actinomycosis of the jaw-bone of an ox. The dark areas and the broken-down 
part in the center of the picture are foci of the disease. The whole bone is enlarged. 

tend to undergo changes similar to those already described. The sur- 
rounding lung tissue frequently becomes indurated from interstitial 
pneumonitis. Extension may occur to the pleura, pericardium, and 
mediastinal tissues. 

In the case of actinomycosis of the intestinal tract there are first 
elevations of the mucous membrane, the disease involving the mucosa 



DISEASES DUE TO BACTERIA 



363 



and the submucosa. Subsequent softening of these leads to the forma- 
tion of ulcerations. Extension to the peritoneum and to the other organs 
of the abdomen may take place, 

In any case of actinomycosis a penetration of the blood-vessels or 
lymph-channels may lead to metastases. Thus in actinomycosis of 
the abdominal cavity the liver is frequently involved; and other parts 
of the body may be similarly affected. Actinomycotic lesions of the 
brain (abscesses) are sometimes seen in such instances. In other cases 
of cerebral involvement there may be no evidence of the original focus 
or point of entrance of the germ. 

Microscopically, the characteristic feature of this disease is the 
parasite itself surrounded by leukocytes in considerable numbers, with 
some epithelioid cells and occasionally giant cells. When the process 
tends to a favorable termination by cicatrization, fibrous-tissue formation 
proceeds in the usual manner. 

Pathological Physiology. — The actinomyces is mainly active as a 
local parasite, the general disturbances of health being comparatively 
slight. There is a marked tendency to limitation or retardation of the 
disease, and sometimes this is effected completely. 

MYCETOMA 

Mycetoma, or madura-foot, is an infectious disease occurring in 
India and elsewhere, and probably caused by several organisms, cer- 
tainly two, grouped under the name Streptothrix or Actinomyces madurce. 
Babes asserts that the black variety is due to a mucor or aspergillus. 
The disease is not infrequent in Madura, Delhi, and other parts of India, 
and has been observed in Africa, southern Europe, and America. 

Etiology and Pathological Anatomy. — As its name indicates, the 
disease affects the foot, and usually follows injuries, particularly thorn 
wounds. In rare cases the hands or other parts are affected. At first 
there is nodular inflammatory swelling, beginning on the plantar surface 
or dorsum of the foot and spreading to the sides. These swellings are 
hard and painless. Later, softening occurs and rupture takes place. 
Thin, watery pus is discharged, and this contains grayish or reddish 
granular bodies or black granules resembling particles of gunpowder. In 
the former case the term "pale mycetoma" is applied; the latter variety 
is called black or melanoid. In the later stages of the disease discharging 
sinuses my remain, while newer nodules, in turn, are formed and soften. 
Finally, the member affected becomes greatly deformed, the portions not 
involved growing thin, while the diseased part increases in size. Death 
occurs from exhaustion or complications. 

Histologically, the nodules resemble large tubercles, but are highly 
vascular. The bulk of the growth consists of granulation tissue cells, 
those in the center being small, those near the outer edge often large and 
containing two or more nuclei. True giant cells are rare. In the center 
may be found a branching micro-organism, called Streptothrix madurce 
(Vincent). This stains by Gram's method and sometimes shows some- 
what bulbous swelling of the ends of the threads and their branches 



364 



A TEXT-BOOK OF PATHOLOGY 



(Fig. 139). The mycelia of the black variety of mycetoma are described 
by Laveran as thicker and coarser than those of the pale form, and he 
believes the organisms are of a distinct variety or species. Around the 
organism may be seen an area of degeneration, having a striate arrange- 
ment suggesting that seen in actinomycosis. Extensive degeneration and 
pus formation occur in the center of the diseased areas in the later 
stages; and hemorrhage may occur from the new blood-vessels. Histo- 
logical examination of the granules in the pus shows the micro-organisms 

in the form of interlacing threads. 
Bodies resembling spores have oc- 
casionally been described. 

The organism has not as yet been 
definitely classified. It is certainly 
allied with the actinomyces, but prob- 
ably not identical. It has been cultivated 
upon various media, particularly in- 
fusions of hay and the like, rendered 
slightly acid in reaction. It forms 
small nodular and hard growths, which 
become rose-red in color when they 
cling to the sides of the test-tube near 
the surface of the liquid, or brownish 
when they sink to the bottom. Upon 
agar isolated grayish or, later, rose-red 
clusters are formed. Inoculation ex- 
periments have thus far met with little 
success. Local reaction has been so 
produced, but not a definite disease. 
Several investigators have reached the 
conclusion that there are two or more 
kinds of micro-organisms that have an 
etiological relation to cases of Madura 
foot. It has in particular been suggested 
that the white and black varieties of the disease have a distinct 
bacteriology. These views need further confirmation. 

The foregoing diseases due to the so-called Trichomycetes represent 
fairly well defined entities but there are met now and then cases in 
which other streptothrices have caused very definite lesions. Such patho- 
logical changes are encountered in mucous membranes, under the skin 
and especially in the lungs, as firm nodular infiltrates showing a ten- 
dency to become necrotic in the centre. Such conditions are quite com- 
mon in the lower animals but rare in man; too few have been studied 
from both sources to make their classification practicable. 

THRUSH 

This condition occurs in newborn infants and in older children 
or adults who have become weakened by disease. The organism called 
O'idium albicans is a budding fungus, though some believe it a form of 
mould. If some of the milky deposits on the mucous membrane of 
the mouth which characterize the disease be removed and examined 




Fig. 139. — Streptothrix madurse 
in a section of diseased tissue 
(Vincent) . 



DISEASES DUE TO BACTERIA 



365 



microscopically, mycelial threads and conidia are observed. The organ- 
ism may be cultivated upon gelatin plates, in the form of whitish colonies 
on the surface, or granules with radiating processes in the depth of the 
medium. On potato and on bread it forms a white coating. The organ- 
ism is present in the air and in various articles of food, so that infection 
readily takes place. 

The organisms first grow upon the surface of the mucosa, but later 
may penetrate to considerable depth, and may attack blood-vessels. 
If this occurs, metastasis may result, with abscesses in different organs, 
notably brain and kidney. 



Fig. 140. — Thrush fungus (Endomyces albicans) (Kolle and Wassermann) . 

Sprue. — It has been argued by Ashford that sprue is due to a species of 
Monilia, the group to which the foregoing yeast belongs. It has been 
isolated from various parts of the intestinal tract including the 1 ' geograph- 
ical " tongue and the intestinal mucosa. An increase in virulence seems 
to occur when a culture is passed through rabbits. 



This is a subacute infection, chiefly of the skin, caused by forms . of 
yeast, Saccharomyces hominis or S. busse. There are probably several 
different species capable of setting up infection, but their action is 
essentially the same. Saccharomyces tumefaciens and Blastomyces 
dermatitidis are also names given to yeasts causing disease in the skin. 

The yeast is a rounded or elongated (up to 30 yu), doubly contoured, 
highly refractile body, with vacuolated, granular or clear cytoplasm; 
multiplication occurs by budding. The organisms are best stained by 
polychrome methods. They grow with difficulty and require carbo- 
hydrates. They are most easily obtained by inoculating guinea-pigs 
under the skin and culturing the pus. They produce an active cellular 
exudate in which fibrin is abundant. Necrosis is common. A toxin of 
moderate potency is produced. The lesions are said to be primarily 
cutaneous or pulmonary, although some question the latter. The 
spread is probably hematogenic, as scattered abscesses and osteomye- 




SACCHAROMYCOSIS OR BLASTOMYCOSIS 



366 



A TEXT-BOOK OF PATHOLOGY 



litis may occur. The lesion is usually a mixture of suppuration and 
granulation tissue (see p. 155). The disease may be transferred to the 
lower animals. No immunity reactions are of value. 

Coccidiosis, or Oidiomycosis, is an acute infection due to the Coccid- 
ioides immitis, an organism closely related to the Oidia, and has some of 
the characters of both the classes, Blastomyces and Hyphomyces. It is 
a doubly refractile circular body in the tissue, occasionally growing 
out into mycelia, and always doing this in cultures. It develops by 
intracellular sporulation and not by budding. The infection usually 
begins in the skin where its most prominent lesions appear but some have 




Fig. 141. — Blastomyces in pneumonic exudate (from a photograph by Dr. S. S. Kneass) 

claimed that a respiratory tract origin is possible. Locally a sluggish 
subcutaneous abscess forms unaccompained by systemic reaction but a 
few cases of extensive spread, with fever and lung and bone involvement, 
are reported. The lesion resembles a tubercle in the cellular and degene- 
rative characters. Eosinophiles may be present. The origin and means 
of transmission of the last two infections are not known. 

Sporothricosis. — This is a disease consisting of cutaneous eruptions 
and multiple abscesses, usually in the skin, but not infrequently in the 
mucous membranes, muscles, tendons, and mammary gland. It is 
caused by the Sporothrix schencki, after the investigator who first 
described it. The organism appears in several slightly different varie- 
ties. It occurs in lesions as round or oval yeast-like bodies, but on 
cultivation shows long mycelial threads from which grow yeast-like 
spores or gonidia. The spore body measures 3 to 6 by 2 to 4 p. In the 
tissues usually only the yeast-like stage is seen, but short mycelia may 
form. The organism is aerobic and requires the presence of carbohy- 



DISEASES DUE TO BACTERIA 



367 



drate for its growth. The disease is subacute. In addition to the 
above-mentioned lesions, the mould may produce a nodular lymph- 
angitis in man as it can in the lower animals. A disseminated form with 
the moulds in the blood is reported and considered a grave condition. 
The disease is transmissible to the lower animals. The blood contains 
an agglutinin and a complement-fixing body against the mould. For 
histology of the lesions, see p. 155. 

Dermatomycosis. — Besides the above infections, there are several 
moulds which infest the skin and produce more or less specific reactions 
of clinical rather than pathological importance. The following skin 
diseases are included under this heading: Favus, caused by Achorion 
schdnleinii; ringworm, including Tinea tonsurans, Tinea sycosis, Tinea 
circinata, and Tinea versicolor, due to varieties of the genus of moulds 
Trichophyton. The moulds infest the epidermis or penetrate the gland 
ducts. Their action is to cause the epithelium to degenerate and 
desquamate, while a round and polynuclear cell invasion occurs in the 
dermis. Those growing where hairs exist are. apt to spread down the 
hair follicle, plug it up and cause the basal cells to degenerate whereupon 
penetration into the hair shaft may occur. There is little specificity 
pathologically. 

Granuloma pyogenicum, or human botryomycosis, is a granulating 
pyogenic and ulcerative condition of the dermis, penetrating to the sur- 
face, said by some to be due to bacteria, but lately ascribed by others 
to an intracellular protozoon-like body. 

Other Bacteria Not Causing Specific Infection 

the hemorrhagic diseases 

These diseases constitute a group of affections of probably quite 
divergent character, which, however, are similar in presenting hemor- 
rhages in and from the mucous membranes, in the skin, serous sur- 
faces, and in the deeper tissues or organs. 

The general causes of hemorrhage must be considered in connection 
with these diseases. Among the causes capable of producing hemor- 
rhages such as occur in the hemorrhagic diseases are mechanical condi- 
tions, as atheroma or other diseases of the walls of the blood-vessels; 
toxic conditions, such as poisoning by the venom of animals and by 
various blood-poisons, and probably obscure poisons produced in the 
course of anemia or other diseases; infectious conditions, such as occur 
in hemorrhagic variola, scarlatina, etc.; and nervous conditions, as are 
illustrated in the hemorrhages following injuries to the brain and those 
accompanying certain states of cerebral excitation. 

Clinically, the hemorrhagic diseases or purpuras may be classified 
as primary and secondary, the former occurring without any definite 
preceding disease; the latter being symptomatic of various disorders. 
Among the primary there are: (1) infectious forms, including, with 
more or less probability, purpura, scurvy, and various forms of crypto- 
genetic sepsis; (2) toxic forms, as those due to drugs and venom of ani- 
mals; (3) mechanical forms, as, perhaps, hemophilia, to the extent that 



368 



A TEXT-BOOK OF PATHOLOGY 



vascular weakness may be a factor. Among the secondary purpuras 
are: (1) infectious forms, as scarlatina, variola and the like; (2) mechan- 
ical forms, as those due to cardiac and arterial diseases, or embolism; 
(3) toxic forms, as those resulting from intestinal auto-intoxications, 
jaundice, pernicious anemia, etc.; and (4) nervous forms, as those due 
to hysteria, diseases of the brain, etc. 

The underlying conditions in cases of infection whose most im- 
portant manifestation is hemorrhage are to be sought first in the blood- 
vessels and then in the blood. In the former case the posion has a dele- 
terious effect upon the permeability of the blood-vessels, while in the 
latter hemolysis occurs in the blood-stream; thus escape is easy. It is 
probable that the two actions are to be found in all hemorrhagic 
conditions. 

The infectious purpuras interest us particularly in the present place. 
Various micro-organisms have been "found in different forms of hemor- 
rhagic disease. Kolb described a bacillus pathogenic for animals which 
occurred in 5 cases of hemorrhagic purpura. Babes and Oprescu isolated 
a bacillus from one case of hemorrhagic septicemia, and others have 
found various micrococci, especially the streptococcus. It is not un- 
likely that various micro-organisms may assume a peculiar virulence 
and acquire the power to produce hemorrhages under certain circum- 
stances. 

Some recent investigations seem to indicate that scurvy is a tox- 
emia due to poisons generated in preserved meat foods as a result of 
autolysis. In scurvy, however, several micro-organisms have been 
described, but the one which has the best claim for consideration is 
that discovered by Babes, a delicate bacillus occurring in the gums. 
Streptococci were found in association with it. Some Japanese investi- 
gators have recently claimed to have discovered a specific bacillus in 
the blood and viscera, agglutinable by the serum of scorbutic patients. 
Present indications, however, do not very strongly substantiate the 
probability of a bacterial cause for this disease. 

PROTEUS INFECTION 

The Bacillus proteus and its several sub varieties occur in decom- 
posing animal matter and in association with necrotic and gangrenous 
processes in the hving body. The organism is a small, motile bacillus, 
occurring in pairs and less often in chain formations. It is abun- 
dantly supplied with flagella. 

Cultivation and Demonstration. — The organism grows very well at 
ordinary temperatures, and forms characteristic growths on gelatin- 
plates. At first yellowish colonies with outgrowths are formed; the 
gelatin liquefies, and the outgrowths move about in a tortuous manner 
and become separated from the original growth. Peculiar figures 
are formed, and the term Bacillus figurans has been applied. The cul- 
tures have a putrid odor. The organism is readily stained with ordinary 
solutions like carbol-fuchsin. 

Pathogenicity. — Injected intravenously in animals, hemorrhagic 
vomiting and diarrhea result. In man the bacillus has been found asso- 
ciated with phlegmonous inflammations, gangrenous processes, cystitis, 



DISEASES DUE TO BACTERIA 



369 



pyelitis; endometritis, etc. It probably seldom starts an infection 
since it is practically never present in the absence of pyogenic cocci 
or bacilli. For the lower animals however a considerable virulence 
exists and it is frequently found in pure culture. It is sometimes the 
cause of meat poisoning. 

Infectious Diseases Whose Cause is Not Certainly Known. 

Filterable Viruses 

yellow fever 

Definition. — Yellow fever, or typhus icteroides, is now recognized 
as infectious and transmissible through the bite of a certain form of 
mosquito, the Stegomyia calopus. 

Etiology. — Many different organisms have been described as the 
cause of yellow fever, most prominent of them being the Bacillus ic- 
teroides of Sanarelli. The latest contribution to the etiology is by 
Noguchi who found a tiny organism, Leptospira icteroides, in blood and 
organs of yellow fever cases and transmitted the disease to lower animals. 

The Role of Mosquitoes. — The experiments of Reed, Carroll, and 
Agramonte demonstrated the importance of mosquitoes as agents 
in the transmission of the disease. It was definitely proved by Reed 
and his associates that a special form of mosquito, the Stegomyia fas data, 
carries the contagion from one person to another. The germ must 
pass a certain incubation period in the body of the mosquito, as the 
bite of the latter is not found to cause infection until after an inter- 
val of twelve days or more from the time it has fed on the yellow-fever 
patient. A bite at an earlier period after contamination did not confer 
immunity against a subsequent attack of the disease. This indicates 
that a cycle of development must occur in the mosquito. Without the 
Stegomyia fasciata there can be no yellow fever, as there can be no malaria 
without Anopheles. The mosquito must feed on a yellow-fever patient 
during the first three days of the fever, and after the twelve-day period 
is infective for #t least fifty-seven days. The spread of the disease is 
checked by preventing the mosquito from biting patients or by its whole- 
sale destruction. The blood of patients is infective even after passage 
through a Berkefeld filter. One attack confers immunity. Experiments 
were conducted directly on non-immune volunteers, and the transmissi- 
bility of the disease was positively proved. The incubation period 
of the disease, the time elapsing from the time of the mosquito '& bite up 
to the first definite symptoms, varied from forty-one hours to five days 
and seventeen hours. The results of the practical measures of quaran- 
tine instituted at Havana in accordance with Reed's work — destruction 
of all mosquitoes and careful exclusion of mosquitoes from the patients, 
with entire disregard of clothing, bedding, etc- — show that the disease 
is not directly contagious. Non-immune nurses attend yellow-fever 
patients with impunity. The disease can also be transmitted experi- 
mentally by subcutaneous injections of blood taken from patients in 
thefirst and second days of the disease, which proves the presence of the 
parasite, in the blood at least, in the earlier stages of the disease. The 

24 



370 



A TEXT-BOOK OF PATHOLOGY 



observations of Noguchi in 1918 record the discovery, by dark field 
microscopy and guinea-pig injection, of a minute spirochete, 4-9 m. long 
and about 0.2m. wide, with tapering ends; it exhibits a boring and rotary 
movement by which it moves within tissues. Inoculations of yellow 
fever blood into guinea-pigs results in an infection similar, during life 
and at post mortem, to the disease yellow fever. Cultivation from 
human blood and the body of guinea-pigs, has been successful in deep 
serum tubes with the addition of Ringer's solution and bits of tissue. 
The spirochete will pass through a porcelain filter or at least it can 
assume a fine granular form that will pass through, since the filtrate 
is infective for guinea-pigs. Serum of recovered cases will give a 
Pfeiffer reaction with the spirochete and animals are protected against 
subsequent infection by preliminary injections of immune blood. The 
organism does not stain well and can only be studied conveniently under 

the dark field. Its growth oc- 
curs best at 37°C. but it may 
remain alive at 26°C. for many 
months. Sunlight, drying and 
bacterial contamination soon 
kill it. It seems to disappear 
from the blood after the first few 
days of the attack but it prob- 
ably settles in the organs, since 
m guinea-pigs spirochetes are 
more numerous in the liver at 
the height of the attack. The 
urine may contain the organism. 

The work of Noguchi is in 
no way inconsistent with the 
reports of Reed but indeed helps 
to explain some points. For 
example the reason why mos- 
quitoes only become infected when biting early in the attack is because 
the organisms leave the blood and settle in the organs. The twelve 
day development period in mosquitoes is the time necessary for the few 
spirochetes ingested to accumulate sufficiently to infect a person. 

Pathological Anatomy. — The lesions of this disease are mainly 
those of the internal organs- — liver and kidneys. In the liver extensive 
fatty degeneration leads to swelling and light color of the organ, and 
on section there may be a mottled appearance due to the alternation 
of healthy and fatty areas. In the kidneys degenerative changes of the 
parenchyma and extravasation of blood are associated in varying pro- 
portions. The appearance may be that of an acute hemorrhagic nephri- 
tis or, more particularly, that of degenerative nephritis. Hemorrhages 
in the mucous and serous surfaces are frequent, particularly extravasa- 
tions in the mucosa of the stomach, whence probably come the dark 
brown fluid commonly met in this organ and which is ejected as " black 
vomit." The skin, mucous surfaces and organs are usually pigmented 
a distinct yellow-brown color. 

Pathological Physiology. — The organism of yellow fever probably 
produces abundant toxin. 




Fig. 142. — Leptospira icteroides in the 
blood of a guinea pig experimentally in- 
oculated with culture of strain from a 
patient. Fixed in methyl alcohol and 
stained with Wright's stain; X 1000. 
(Noguchi, in Journal of Exper. Med., 
Vol. xxix). 



DISEASES DUE TO BACTERIA 



371 



ENCEPHALITIS LETHARGICA 

A form of encephalitis sometimes appears in epidemic form, so 
closely connected with influenza, chronologically at least, that many 
observers associate the two diseases. There was a large number of cases 
after the last two pandemics of influenza and from many observers 
comes the report that the majority of their patients had had this disease. 
The lesions are so similar to certain other acute encephalitides that one 
can assume the existence of other factors and not limit the cause to 
the virus of influenza. The condition is expressed clinically by head- 
ache, nausea, vomiting, nervousness growing into delirium which is 
in turn succeeded by somnolence and then coma. Paralyses of the 
eye muscles are apt to occur and motor tract lesions have been observed. 
The spinal fluid is negative except that some writers report successful 
inoculation of monkeys by using it. A filterable virus is also found in 
the brain and cord and possibly in the blood. Bacteria have been found 
in cultures but they are not generally accepted as of importance. Grossly 
the brain and pia are deeply reddened and soft, but no localized lesions 
are to be found. In some cases the minute lesions are limited to the 
basal ganglia while in others the cortex is included; at all events gray 
and white matter are involved at all places. There are perivascular 
and diffuse infiltrations of round cells, while occasionally one sees large 
phagocytic cells perhaps derived from those just mentioned; polynuclears 
are scarce if present at all. Some authors report endo-arterial hyperpla- 
sia while others did not discover it. Hemorrhages are few but some 
seeping out of fibrin must occur for it has been seen in the focal collections 
of round cells. In some quarters great emphasis is placed upon peri- 
vascular and intramural round cell increase while in others equal weight 
is laid upon the diffuse infiltrate; it may be that the causative virus 
has been different. The spinal cord is rarely affected. 

TRENCH FEVER 

An infection bearing this name came into prominence during the 
late war when it represented perhaps the greatest single cause of in- 
validism. Since the louse has been convicted of conveying the disease 
this fact will not be astonishing. The incubation period is from one 
to three weeks. The fever is of a very irregular kind, sometimes appear- 
ing for a few hours never to return, at others running an irregular course 
for several days or weeks, at still others adopting a recurrent form of 
regular or irregular intervals. The onset is usually sudden with head- 
ache, muscular pain and often a conjunctivitis. There may be a rash 
suggesting typhoidal rose spots. The spleen is enlarged and firm. The 
blood shows a mild leucocytosis with mononuclears predominating; 
leukopenia may exist between paroxysms. Perhaps pain is the most 
important and valuable diagnostic sign since it is especially marked 
along the shin and in muscles, unaccompanied by swelling or acute 
tenderness. The disease is rarely fatal so that information of its essential 
pathology is not at hand. The virus seems to be transmitted chiefly 
by lice the feces of which contain it so that scratching may permit the 
penetration into the body. Blood and urine of patients are said to 



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A TEXT-BOOK OF PATHOLOGY 



contain the virus. By some observers, successful nitration of the virus 
is reported; by others this is denied. Heating up to 80°C. does not seem 
to destroy the power to transmit the disease. Experiments seem to 
indicate that after a louse bites it requires seven days before it is capable 
of infecting a human being and that this power lasts for twenty-three 
days; virus is not transmitted to offspring. While the louse has been 
convicted of being a carrier of this disease there is nothing in the present 
evidence to show that other methods of transmission may not exist. 
Spirochetes and bacteria have been thought the cause of the condition 
but no satisfactory data are now at hand concerning any one of them. 
No immunity follows an attack and very few persons have a natural 
immunity. 

MEASLES 

Measles, or rubeola, is an infectious and contagious disease, in 
all probability due to some micro-organism. A number of micro- 
organisms have been described. Several observers (Canon and Pielicke, 
Czajkewski) have found a bacillus somewhat resembling that of in- 
fluenza; others have found bacilli resembling the pseudodiphtheria bacil- 
lus, but the bacteriology is still unsettled. Doehle described a protozoan 
organism occurring in the blood. Hektoen has inoculated healthy per- 
sons with the blood from cases of measles and has demonstrated the 
transmissibility. 

The disease is at present regarded as due to an ultramicroscopic virus 
which will pass through a porcelain filter. The virus is present in the 
blood, buccal and nasal secretions from 3 to 4 days before the eruption 
appears remaining until the discharges from nose and throat cease, and 
can be transmitted to monkeys, in which it produces an atypical infection. 
It has not been cultivated. 

Mild catarrhal inflammations of the faucial, nasal, and conjunctival 
membranes and of the bronchial mucosa are customary lesions. With 
these conditions is associated some congestive and inflammatory enlarge- 
ment of the regional lymphatic glands. In severe cases pseudomem- 
branous inflammations of the throat are sometimes met with, and 
bronchopneumonia and parenchymatous nephritis are occasional com- 
plications. The lung involvement chiefly concerns the smaller bronchi; 
the walls and immediate surroundings are densely infiltrated, together 
with swelling arid degeneration of the epithelium . At times a productive 
change occurs within the air tube leading to its obliteration. There is 
in addition a very decided tendency toward interstitial pneumonia. The 
eruption of the skin is the visible evidence of a moderate dermal and sub- 
dermal inflammation. Mallory describes the histology of the changes 
in the skin as being a mononuclear or endothelial perivascular infiltration, 
the cells migrating therefrom to areas of softening high in the epiderm. 
Focal necroses of the liver have been described. Many of the lesions are 
doubtless caused by secondary infections. 

SCARLET FEVER 

Scarlet fever, or scarlatina, is an infectious and contagious disease 
probably due to a micro-organism. A variety of organisms have been 



DISEASES DUE TO BACTERIA 



373 



discovered in cases of scarlet fever, but none as yet has proved to be 
specific. Among other bacteria the pyogenic micrococci (streptococci) 
have been regarded as etiological agents. This, however, is by no means 
established. Protozoan organisms have also been described (Doehle). 
Mallory has described under the name of Cyclasterion scarlatinale struc- 
tures which present the appearance of protozoa. 

The virus is now believed to be filterable and ultramicroscopical. 
An atypical infection is produced in monkeys by injection of a patient's 
blood during the height of the attack. 

The lesions within the skin consist of leucocyte infiltration about the 
blood-vessels, moderate edema of the corium and great activity in the 
basal epithelium. 

Lesions of the mucous membranes and glands similar to those of 
measles, but usually more intense, are generally present. Suppuration 
of the glands of the neck is a possible termination, and severe inflam- 
mations of the throat, middle ear, larynx, and trachea, with endocarditis 
or pericarditis, are much more frequent than in measles. Many of these 
complicating conditions are caused by secondary infection with the Strep- 
tococcus pyogenes. Diphtheria (as contrasted with streptococcic lesions 
of the throat presenting a similar appearance) is not rare as a complica- 
tion. Glomerulo-nephritis is a lesion of great clinical interest, while 
focal necroses of various organs are observed in fatal cases. 

MUMPS 

The bacteriology of mumps is uncertain. Charrin and Capitan 
isolated a number of organisms, mainly micrococci and motile bacilli. 
A number of other authors subsequently obtained similarly indefinite 
results. Laveran and Catrin in 1893 found a diplococcus. 

The pathology of mumps is that of an acute inflammation of the 
parotid or submaxillary gland. This rarely terminates in suppuration 
or, on recovery, in induration of the gland. A rare but serious complica- 
tion is meningitis which assumes a serofibrinous form. 

VARIOLA AND VACCINIA 

Variola is an acute contagious disease characterized by a general 
cutaneous and mucous membrane eruption with symptoms of septicemia. 
Vaccinia is a localized cutaneous lesion with mild general manifestations 
due to the inoculation of variola virus after it has passed through a cow. 
The virus is apparently the same with, in the case of vaccinia, some modi- 
fication of virulence but not of immunizing power for its intentional 
introduction produces practically as great a resistance as naturally fol- 
lows the spontaneous disease variola. It has been propagated under 
careful laboratory conditions and will pass through a porcelain filter. 

A number of bacteria have been described from time to time in these 
diseases, and various micrococci in particular have been found in the 
pustules, but none of these can be considered as specific. Several bacilli, 
one form resembling the diphtheria bacillus, have been recently described. 

In 1887 Pfeiffer and van der Loeff independently described a proto- 
zoan parasite of the order Sporozoa, which occurs in the cells of the rete. 



374 



A TEXT-BOOK OF PATHOLOGY 



This organism was found in variola as well as in vaccinia. Pfeiffer, 
Guarnieri, and other investigators found that by inoculation of the 
cornea of rabbits large numbers of the supposed parasites make their 
appearance in the epithelial cells. These organisms are rounded bodies 
lying in the protoplasm of the cells, sometimes singly, sometimes in 
groups of two or three. Slow ameboid movements are visible and the 
organisms present one or more nuclei. Spore formation has been ob- 
served by several investigators. Guarnieri suggested the name Cytoryctes 
variolce seu vaccince. 

Councilman, Magrath, and Brinckerhoff in 1903 confirmed the find- 
ings of Guarnieri in 1892 and of Wasielewski some years later as to cell 
inclusions in lesions of vaccinia and variola. They look upon them as 
living organisms and the probable etiological factor of vaccinia and 
variola. In vaccinia the cytoryctes occurs as a structureless mass in 
the cytoplasm, where it is thought to undergo asexual division by break- 
ing up into small round segments. In variola the parasite is said to 
invade the nucleus also, undergoing there segmentation into ring-like 
bodies; this is supposed to be the sexual phase. 

The formation of the exanthem may be due to the infected endo- 
thelial cells of the capillaries or lymph-spaces being carried to the skin 
capillaries by the blood-current. No differential method of staining has 
as yet been offered. The nature and significance of these supposed 
organisms have not yet been positively determined. Some authorities, 
as Ewing, look upon them as products of cell degeneration. Lately the 
view has been defended that they are the Chlamydozoa of Prowaczek, 
probably due to a virus acting upon the chromatin, with lysis thereof. 

Secondary infections with various micrococci or other organisms are 
common in small-pox and vaccination, and may play an important part 
in pustulation, and in the more definite complications, such as septicemia, 
pneumonia, hemorrhagic septicemia, erysipelas, and the like. 

The disease is believed to be transmitted by direct personal contact 
or by objects freshly soiled with discharges from patients since the virus 
is present in skin scales, sputum, urine and feces; flies cannot be exempt 
from suspicion. After an incubation period of 12 to 14 days, a maculo- 
papular eruption appears upon the skin and occurs also upon mucous 
surfaces. This shortly becomes vesicular, then pustular, after which 
drying may form a crust over a dull red base. The skin lesion consists 
of hydropic degeneration of the prickle layer of epithelium, directly over 
the basal cells, which goes on to rupture of the cells and the collection 
of fluid. Fibers derived from the remnants of cells, support the vesicle 
thus formed and usually they remain until pus appears, during their 
existence causing a dimpling on the surface. Leucocytes appear late 
probably in response to pyogenic mixed infection. The rete is often not 
destroyed but when this happens, u pock marks" remain. Lesions of a 
similar nature occur upon mucous membranes causing shallow ulcerations. 
In the internal organs after death one usually encounters lesions that 
seem to be the effect of mixed infection but there are a few histological 
pictures which are the result of the virus of small pox. Such changes are 
seen in the bone marrow and testes in the form of mononuclear cell infil- 
trations which not infrequently go on to necrosis. 



DISEASES DUE TO BACTERIA 375 
VARICELLA 

The etiology of chicken-pox is even less definitely determined than 
that of small-pox. Pfeiffer discovered the same organism described by 
him in vaccinia and variola. Bacteria of one sort or another have been 
occasionally found. The pathology is essentially the same. 

TYPHUS FEVER 

An acute epidemic disease attended with a fairly typical clinical 
course and macular eruption, supposed to be transmitted by the louse, 
Pediculus vestamenti. The virus is found best in the blood toward the 
end of the disease, is filterable, and may be transmitted to monkeys. 
Many different organisms have been discovered and described, but none 
are now believed to be the real cause. The organism now receiving 
most attention is a non-motile rod with a palely staining central area, 
circulating in the blood. It is said to grow feebly under anaerobic con- 
ditions if cultures are made between the sixth and ninth day of the attack. 
Agglutinins and complement fixing bodies appear during an attack. 
Rocha Lima believes he has found a protozoon in the louse and that he 
can produce typhus in guinea-pigs with it. It has been suggested that 
the two organisms are the same but at different stages of development. 

The severe typhus of Mexico is called "tabardillo." There is a mild 
infection called "Brill's disease," after the observer, believed to be a 
sporadic form of typhus. It has been observed among the Hebrews of 
New York and other American cities. 

The lesions of typhus fever suggest an intense infection and intoxica- 
tion. The blood is often dark-colored and rapidly putrifies. Various 
organs, such as the liver, kidneys, and heart, show pronounced cloudy 
swelling or fatty degeneration of the cells. The spleen is notably en- 
larged, often quite soft, and may present infarctions due to thrombus 
formation. 

Inflammations of the mucous membranes, especially bronchitis, 
pharyngitis, and laryngitis, are common, and pneumonia is a frequent 
result. 

RABIES 

Etiology. — We have every reason to believe that rabies is due to a 
specific germ. In 1903 Negri described an organism which has received 
considerable recognition as the probable specific cause of the disease. 
The "Negri bodies" have been found in the large nerve-cells of the 
central nervous system, especially in the cornua ammonis, in various 
animals and human beings affected with rabies. They are absent in 
other conditions. In early stages of the disease the bodies are sparsely 
present and are exceedingly minute structureless spherules lying in the 
protoplasm of the nerve-cells. Later the bodies increase in number and 
size and contain one or more darkly staining granules. Stained by the 
Nocht-Romanowsky method the bodies are robin-egg blue, the granules 
darker in color. 

Virus. — In rabic animals the virus is found principally in the saliva 
and in the central nervous system. It is occasionally known to pass into 
other organs, such as the lacrimal gland and the pancreas. It is never 



376 



A TEXT-BOOK OF PATHOLOGY 



found in the blood or in the liver, spleen, kidney, or the muscle tissues. 
The contents of the stomach may contain it, owing to the swallowing 
of the saliva. It affects principally the central nervous system, and is 
found in the most concentrated form in the medulla oblongata. The 
virus is usually present in the saliva for three days before the animal shows 
any symptoms of madness, and it may be present eight days before any 
symptoms appear. It may be present in the central nervous system 
two days before the appearance of any symptoms. The symptoms do 
not show themselves until the poison or virus has remained in the nerv- 
ous tissue long enough to produce structural and functional change. 
After it is introduced into the body it undoubtedly " multiplies itself" 
during the period of incubation. It is a " solid body," as it may be 
removed from the saliva by filtration through porcelain. There is, how- 
ever, almost undoubtedly a stage of development of the virus when it is 
small enough to pass through the filter. An emulsion of brain of an 
infected dog will give a filtrate infective for rabbits. It is found in 
human milk, tears, aqueous humor, and cerebrospinal fluid. The virus 
penetrates to the nervous system by following the nerve-trunks from the 
site of injury to the spinal cord. This has been proved by comparison 
of portions of the cord and of the nerves at varying periods after inocu- 
lation. The virus is destroyed by drying and by the action of light. 

Noguchi has lately demonstrated that the virus of rabies may be 
cultivated upon anaerobic serum-cultures. It takes the form of minute 
masses of chromatin surrounded by a clear zone and a membrane, and 
as very minute granular and somewhat coarser pleomorphic chromatoid 
bodies. The former multiply by budding and division and suggest 
protozoa. Similar pictures may be found by dark-field examination of 
hydrophobia brains. The bodies are from 1 to 12 /x across. 

The loss of virulence by drying is gradual and regular; hence this is 
taken advantage of for the production of " vaccine." The virus is com- 
pletely destroyed at a temperature of 50° C. (122° F.) in one hour. It 
remains uninjured by exposure to extremes of cold — 10 or 20 degrees 
below zero. 

The Danger from Bites. — The richer the nerve-supply, the greater the 
danger, and punctures are more dangerous than lacerated wounds. The 
wolf, the cat, and the dog, in the order named, are the most dangerous 
animals. 

Period of Incubation. — 'Man, forty days; cats, fourteen to twenty- 
eight days; dogs, twenty-one to forty days. Other animals vary from 
fourteen to fifty-six days. 

The Season. — More frequent during the period from April to Sep- 
tember than any other part of the year. 

Preventive Inoculation. — Pasteur devised a method of treatment which 
consists essentially in successive inoculations with emulsions of spinal 
cords of increasing virulence. The virulence of the material used for 
the first inoculations is decreased by drying the cords for twelve to six- 
teen days; injections are given daily using at each successive dose a bit 
of cord dried for a shorter period, therefore increasingly virulent, until 
fifteen to eighteen injections are given. The virus used is called " virus 
fixe" because it is of uniform virulence, a condition obtained by repeated 



DISEASES DUE TO BACTERIA 



377 



passage through rabbits until it will always produce the disease in the 
same dose in the same time. There is no uniformity of virulence in the 
so-called " street virus," that is, the form isolated from individual eases 
among human beings and dogs. 

Pseudohydrophobia or Lyssophobia. — This is simply a condition of 
fright, and the patients invariably recover. 

Pathology . — Gross Appearances in Organs. — There is no gross lesion 
that can be considered specific of the disease. The cadavers are apt to 
be emaciated and to become putrid rapidly. The blood is usually dark 
and thick. The brain and the membranes may be congested, and may 
even show slight hemorrhages. The gastro-intestinal tract and the 
respiratory tract may be congested and also show slight hemorrhages. 
Rabid dogs frequently swallow wood, straw, stones, and the like, which 
are found in the stomach postmortem. 

Microscopical Appearance. — There is nothing distinctive outside of 
the nervous system. Changes are found in the ganglia of the cerebro- 
spinal and sympathetic systems, and are especially marked in the plexi- 
form ganglion of the pneumogastric nerve and in the Gasserian ganglion. 
Normally, these ganglia are composed of supporting tissue holding in its 
meshes the nerve-cells. These nerve-cells are surrounded by an endo- 
thelial layer and capsule. The rabic virus brings about an abundant 
multiplication of the cells lining this capsule, leading finally to the de- 
struction of the normal ganglion, and leaving in its place a collection of 
round cells. All ganglion cells are not markedly changed; some are 
slightly or not at all changed; others are entirely destroyed. These 
changes are particularly marked in the dog, less so in man, and still less 
so in the rabbit. The ganglion of the pneumogastric nerve is the one 
generally chosen for examination, and it should be removed immediately 
after death and placed in absolute alcohol or in formalin solution. 

RHEUMATISM 

Definition. — Acute articular rheumatism is probably an infectious 
condition; the nature of the infectious agent, however, is uncertain. 

Etiology. — The manifestations of rheumatism agree very well with 
those of infectious diseases, and some of the lesions frequently compli- 
cating the disease, such as endocarditis, are invariably infective. The 
relationship between tonsillitis and rheumatism has been explained by 
some as that between primary and secondary disorder. It is supposed 
that the infectious agents effect an entrance into the body through the 
tonsils, causing primary tonsillitis and secondary general infection, with 
localization in the joints. In other cases it has been held that the organ- 
isms enter through abrasions of the skin or in other ways. 

Leyden and others have described a streptococcus, and it has been 
shown that this organism is capable of producing arthritis, endocarditis, 
and pericarditis in experimental animals. A considerable number of 
recent investigators have isolated a micrococcus or streptococcus from 
cases of rheumatism and have succeeded in producing joint lesions, 
endocarditis, and pericarditis in animals inoculated with it. Others, 
however, have produced similar lesions with streptococci from other 
sources. 



378 



A TEXT-BOOK OF PATHOLOGY 



The organism now receiving most attention is the Streptococcus rheu- 
maticus of Poynton and Paine. This is a hemolytic acidifying diplo- 
coccus requiring blood for its best cultivation. It has been found in 
synovial fluids and tissues, in the blood, and in heart-valve vegetations. 
It produces arthritis and endocarditis in experimental animals. 

Achalme described a bacillus which he and others found in a number 
of cases of acute articular rheumatism, but it is so similar to Welch's 
bacillus that it has not been generally accepted. 

The fact that one organism or another produces inflammatory lesions 
in the joints, endocardium, or pericardium of animals when injected in- 
travenously does not prove a specific relation of the organism to rheu- 
matism. Doubtless various organisms are capable of producing such 
lesions, and it is not improbable that the clinical disease rheumatism 
may include a variety of infections. 

(For the pathological anatomy of rheumatism, see Diseases of the 
Joints.) 

In regard to the general pathology of the group of clinical pictures 
under the heading of infectious rheumatism, there are but two changes 
that deserve special discussion; one is the tendency to affect serous mem- 
branes other than the synovia, the other is the peculiar myocardial 
lesions discussed under acute myocarditis. The effects of the virus of 
the disease are primarily productive and not degenerative, as, for example, 
is seen in the adhesive pericarditis. 

DENGUE 

This is an acute infection common in the tropics, due to a filterable 
virus, transmitted by the mosquito Culex fatigans. The virus is in the 
blood. There are fever, with an intermission, rheumatoid pains, and 
varied skin eruptions. One attack gives no immunity. 

POLIOMYELITIS 

This disease of the central nervous system has assumed a position 
of great interest during the past decade, for during that time it has been 
pandemic, at least in Europe and North America. It was formerly 
known as a sporadic disease of childhood, but its recent manifestations 
have been those of a transmissible epidemic disease affecting almost 
any age, though especially frequent in childhood. 

The infection begins with a mild febrile attack, to which is shortly 
added muscular and joint pains, followed by palsy, and later by distinct 
paralysis. (For the pathology of the disease, see Nervous System.) 

Etiology. — The exact nature of the causative agent of this disease is 
not yet certainly known, but Noguchi has lately been able to cultivate 
from the central nervous system a tiny, poorly staining, bacterium-like 
body, with cultures of which he claims to be able to produce the disease 
in monkeys. Not only has this observer been able to grow these "globoid" 
bodies, but he has found them in sections of nervous tissue. Rosenow 
and his associates have reported the discovery in the same tissue as 
Noguchi used, of an organism which grows like a streptococcus and 
assumes in anaerobic culture, granular forms small enough to pass 



DISEASES DUE TO BACTERIA 



379 



through a filter. With cultures of this, it is claimed that all the tests of 
specificity may be used as with the foregoing globoid bodies. 

While little is as yet known of this tiny bacterium, much has been 
learned of the distribution and behavior of the virus. It is to be found 
in the brain, spinal cord, ganglia, spinal fluid, nasal mucosa, lymphatic 
organs, and intestinal contents. If emulsions of parts containing the 
virus be injected into the brain of a monkey the animal will develop 
symptoms, signs, and the pathology of poliomyelitis. If, instead of 
the emulsion, a filtrate of it, through a Berkefeld filter, be used, infection 
will also result; the virus is, therefore, filterable. Heating to 50° C. 
(122° F.) one-half hour destroys the virus, but it will withstand drying, 
50 per cent, glycerin, and tissue autolysis. The virus is said to be con- 
stantly in the nasal secretions of infected persons, sometimes in those of 
attendants, and also in surroundings, notably in dust. 

Transmission. — Two theories are proposed for the transmission of 
poliomyelitis: first, that it is spread by insects; and, second, that con- 
tact, direct or indirect, is responsible. 

The insect transmission theory is based upon the appearance of the 
disease usually in summer, and upon the discovery by Rosenau that it 
was possible to transmit the disease from monkey to monkey by the 
bite of the stable fly (Stomoxys calcitrans). 

The contact infection theory is based upon the fact that the virus 
is present upon and in the nasal mucosa of patients and healthy attend- 
ants. The latter are suspected of being carriers. Much more impor- 
tant than these, however, are the so-called "abortive" cases of polio- 
myelitis. These are instances in which only a mild febrile affection 
occurs, but which do not go on to palsies, or, at most, show only 
transient weakness, therefore, so atypical that they escape recognition, 
and, going abroad, actively disseminate the virus. 

The nose as a portal of entry gains somewhat in probability when one 
considers the short distance the virus has to travel to reach the central 
nervous system by passing along the olfactory tract. 

Immunity. — One attack of poliomyelitis, either natural or experi- 
mental, gives immunity, and the serum of recovered cases can be used 
therapeutically but no antiserum induced by inoculation of the lower 
animals is as yet reliable. The serum of an immune person or animal 
does, however, possess the power to neutralize the virus. If such a 
serum and a known virus be mixed, incubated, and injected into a mon- 
key, no paralysis will occur, while a control animal injected with the 
same virus not exposed to the immune serum will develop poliomyelitis. 
This test has made it possible to detect abortive cases, because no unin- 
fected person gives serum with this property. 

FOOT-AND-MOUTH DISEASE 

This infection of cattle may be transmitted to human beings who 
use milk from affected cows, or directly from infected animals. There 
is a vesicular eruption in the mouth and on the feet and hands com- 
parable to the lesions in cows. The virus is in the vesicular fluid; 
it has not been cultivated, but is filterable. One attack probably 



380 A TEXT-BOOK OF PATHOLOGY 

gives no immunity; the blood-serum has therapeutic and preventive 
properties. 

TRACHOMA 

This is a transmissible disease of the conjunctiva characterized by- 
tiny granulations on the palpebral surfaces, said by some to be due to 
an invisible filterable virus ; by others it is believed to be caused by an 
influenza-like bacterium. Some observers have found an intracellular 
body which they believe to be the cause. This has been placed 
among Prowaczek's Chlamydozoa. (See chapter on Eye.) 

ROCKY MOUNTAIN FEVER 

This is an acute transmissible disease characterized by evidences of 
general infection, severe pains, and a macular or erythematous erup- 
tion. It is transmitted by the tick Dermacentor venustus. It is practi- 
cally confined to the Rocky Mountain States and is most frequent and 
severe in Montana. It is a disease of adult life, occurring chiefly among 
those who work abroad, and is prevalent in summer. The tick obtains " 
the virus by blood-sucking, and transmits it to another person by biting. 
The female tick transmits it to the eggs and young. The virus is in the 
blood of the patient and is destroyed if this be heated to 50° C. (122° F.) 
or is dried; it will not pass a Berkefeld filter. The disease may be trans- 
mitted by the introduction of infected blood into a guinea-pig, rabbit, 
or horse, and the clinical course in these animals is closely comparable 
to that seen in man. The serum of experimentally infected animals 
has an immunizing value for other animals, but it possesses little if any 
therapeutic power. It has been shown that there is in the infected 
blood and ticks a minute diplococcoid body resembling an organism of 
the hemorrhagic septicemia group. No bacteriological cultivation has 
been successful, so that the cause of the disease is not known. One 
attack, in the laboratory animals at least, confers immunity. The 
essential pathology of the disease, as shown by Wolbach is to be found 
in the skin and testes, consisting in a productive endangitis from which 
arise areas of necrosis. Large mononuclears, probably endothelial in 
origin, dominate the picture, appearing in the intima of the cutaneous ves- 
sels, as a mantle about them, and very prominently in medullary zones of 
lymph tissue. The diplococcoid bodies may be found within those cells. 
Testicular lesions, inflammatory and necrotic, seem to depend upon the 
vascular changes. The organs generally show alterations probably 
dependent upon toxemia. 

THE CHLAMYDOZOA 

This is a name given by v. Prowaczek to certain intracellular bodies 
whose zoological position is not clear, but which have some characters 
suggestive of the protozoa. They undergo a change in appearance 
which has been interpreted by some observers as a metamorphosis. 
No exact life cycle has been accepted by all authorities as certainly 
pointing to protozoal nature. The group includes the Negri bodies of 



DISEASES DUE TO BACTERIA 



381 



rabies, the cytoryctes of vaccinia and variola, the cyclasterion of 
scarlet fever, the trachoma bodies, etc. Prowaczek and his followers 
interpret these chlamydozoa as the result of cellular infestation by 
ultramicroscopical bodies, in response to which the nucleus or nucleolus 
extrudes into the cytoplasm some of its material. The intracellular body 
seems at first to be either a clear space or a minute dot until it is sur- 
rounded by the chromatin material as above derived. The chlamydozoon 
then assumes the form of an irregular mass of chromatin with one or 
more clear spaces. It appears in any imaginable form, giving the im- 



Fig. 143. — Chlamydozoa. Trachoma bodies in infected epithelial cells of the 
conjunctiva, a, initial bodies (above) and cluster of elementary bodies (touching the 
nucleus); b, cluster of granules surrounded by mantles; X 2000 approx. (From 
preparation by Fantham.) (From Fantham, Stephens and Theobald, "The Animal 
Parasites of Man.") 

pression of metamorphosis. Cytoplasm seems to form, but if this be 
de novo or only a part of altered cell protoplasm is not known. The 
virus causing these protozoon-like changes within the cell is filterable, 
associated with colloids, and has a predilection for epiblastic tissues. 
Considerable progress in the proper understanding of these structures 
will doubtless be made shortly for some of them have been cultivated 
(Negri and trachoma bodies) and while in cultures were able to produce 
lesions in lower animals. This of course strengthens their claim to 
consideration as independent microbes but does not as yet settle their 
classification. 




CHAPTER X 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 

Protozoa 

Classification. 1 — Class I. JRhizopoda (Sarcodina), forms resembling the ameba, 
and characterized especially by the presence of pseudopods. 

Class II. Flagellata (Mastigophora), protozoa characterized by the presence 
of one or more long lash-like flagella, used for progression or acquirement of food. 

Class III. Sporozoa, forms living as parasites in the tissues of other animals, 
receiving their food only by osmosis. Reproduction by means of encysted spores. 

Class IV. Infusoria (Ciliata), cell-body of fixed shape with cilia; living free 
in water or as parasites. 

Class V. Suctoria, cell-body provided with suctorial tubes. Usually ecto- 
parasites in water animals and plants. 

The protozoa differ from the bacteria in producing a progressive 
disease without evidences of immunity. Trypanosome infection shows 
the presence of some immune bodies in the blood, but any increase of 
antiprotozoal power of the serum does not seem to limit the course 
of disease, nor can the serum be used to immunize another person. 

Some of the protozoa produce a toxin, but most of them exert their 
noxious power by mechanical injury or obstruction, acting with the 
products of tissue destruction or with bacteria. Protozoa do not as a 
class have a pronounced chemotactic power for leukocytes. They pro- 
duce proteolytic enzymes and their activity is followed by an increase of 
acid in their vicinity. 

Most protozoa have tissues of predilection, such as malaria Plas- 
modia, the blood; amebse, the colon and liver; sarcosporidia, the 
muscles. 

Rhizopoda 
entamceba histolytica 

Description. — This organism is an ameboid body from 20 to 30 /x 
in diameter, consisting of a clear protoplasmic refractive outer portion and 
a finely or coarsely granular protoplasm within (Fig. 144). It frequently 
shows vacuoles and sometimes a vesicular nucleus. It presents active 
ameboid movements when studied on a warm stage of the microscope; 
and frequently contains foreign bodies, such as bacteria, pigment-par- 
ticles, and portions of blood-corpuscles or other cells. 

In the movements of the organism pseudopodia are projected from 
some part of the periphery. These at first draw upon the clear periph- 
eral zone, but after their formation the granuloplasm flows into the 

1 Braun, Die tierischen Parasiten des Menschen, 1903, which is essentially the same 
as adopted by Fantham, Stephens and Theobald in the 1916 edition. 

382 



383 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



projected pseudopods. When in unfavorable surroundings the organ- 
ism undergoes a form of change called the encysted state. In this the 
body becomes spherical, the wall is eventually stiff and firm, and 




Fig. 144. — Entamoeba histolytica. Living organisms. Note absence of nucleus. 
All three of the parasites contain red blood-corpuscles; X 750 (Bulletin No. 1, Medical 
Department U. S. Army, 1913). 

usually presents a double contour. The division into a clear and a 
granular protoplasm is lost, the organism being uniformly granular; 
four generative spores are formed. 



Fig. 145. — Entamoeba tetragena. Living specimens. Note nucleus in upper enta- 
meba. The three lower entamebse contain red blood-corpuscles; X 750 (Bulletin No. 1, 
Medical Department U. S. Army, 1913). 






Schaudinn differentiates two forms of the dysentery amebse, calling 
them Entamoeba histolytica (Fig. 144) and Entamoeba tetragena (Fig. 
145). Craig and others now consider them to be different stages of 



384 



A TEXT-BOOK OF PATHOLOGY 



development of the same species, an opinion now held by most parasi- 
tologists. It should be mentioned that there are many genera and species 
which seem able to cause colitis in man and which are distinguished by 
close students of the subject on biological and pathological grounds. The 
one given here as the type is probably the most important and the best 
known. 

Distribution and Pathogenesis. — The parasites reach the bowel 
in contaminated water or in insufficiently cooked and raw food. They 
settle in the organ of predilection, the colon, penetrating by their pseudo- 
pods, between the epithelium to the depths of the mucosa and the 
submucosa. The organism in question has been found abundantly 
in the stools of patients suffering from dysentery. It is readily detected 
in the necrotic particles or the mucus of the stools, and has also been 
found in the tissues of the bowel wall adjacent to the dysenteric ulcers 
and in the liver abscesses secondary to dysentery. 

Liver abscess is a frequent complication or sequel of amebic dys- 
entery. The protozoa reach the liver through the blood-stream, prob- 
ably by penetrating radicles of the mesenteric vein, and are found in the 
wall of the abscesses. Whether they alone can produce pus is not 
known. There may be abscesses elsewhere. 

Musgrave and Clegg have cultivated amebae with cultures of bac- 
teria, and should a colony grow free of bacteria it may be kept alive 
for a short time an agar media to which extracts of tissue have been 
added. The injection of mucus containing the amebae into the rectum 
of cats and other animals has occasionally produced typical dysentery, 
but this does not prove the pathogenicity of the amebae. Lesions 
closely similar to the natural disease have been produced in monkeys, 
and a human case with very suggestive clinical course was caused by 
swallowing capsules containing amebae. The Entamoeba histolytica 
produces a moderately strong poison which causes cellular necrosis, 
but not much acute inflammation. 

ENTAMOEBA COLI 

This smaller ameba (10 to 20 m in diameter), also differing from the 
Entamoeba histolytica in having a less greenish color, less distinct ec- 
toplasm and endoplasm, less distinct pseudopodia, in the usual absence 
of vacuoles, the almost invariable presence of a nucleus and well-defined 
nuclear membrane, and in rarely ingesting red corpuscles, has been 
found in the feces of from 50 to 70 per cent, of healthy persons in various 
localities. Possibly under certain conditions the ameba may become 
pathogenic; usually it has been found in persons entirely well. Its 
cysts^contain eight spores. 

OTHER AUEBM 

Several other amebae of lesser importance have been discovered. 
Among these are the Entamoeba urinalis, found in the urine in cases of 
cystitis, and several forms met with in the mouth, especially about 
the teeth. Entamoeba buccalis has lately been held responsible for 
pyorrhoea alveolaris. An ameboid organism of uncertain pathogenic 
significance has been discovered in the abdominal fluid of cases of ascites. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



385 



It has been named Leydenia gemmipara. It has a pulsating vacuole 
and nucleus and multiplies by budding or division. 

MAST1GOPHORA (Fiagellata) 

CERCOMONAS HO MINIS 

This organism is a pear-shaped body with a sharp anterior extremity 
provided with a delicate short cilium. The broader posterior end is 
provided with a long, tail-like flagellum. A large and a small variety 
have been described (Fig. 146). The former is the variety usually found 
and is from 10 to 12 /x in length. A minute oval aperture has been 
found at the anterior extremity. 

* b 

Fig. 146. — Cercomonas hominis; A, large; B, small, variety (Davaine). 



Significance. — The organism has been discovered in great numbers in 
various diarrheal conditions, especially in cholera. It has, however, 
been found in the stools of from 10 to 25 per cent, of healthy persons 
in tropical countries and is not known to have definite pathogenic 
powers. 

Other closely allied cercomonads have been found in the urine 
(Bodo urinarius, Cercomonas urinarius). 

TRICHOMONAS INTESTINALIS 

This organism is pear shaped; from 10 to 15 m in length and 7 ix in 
breadth (Fig. 147). The anterior end is blunt; the posterior end is 
prolonged into a sharp, tail-like projection. The 
body is granular and contains one or two bodies 
resembling vacuoles. Near the anterior end at 
one side may be seen a row of ten or twelve 
cilia, which give the organism active motility. 

It has also ameboid movements. Fig. 1 4 7 .—Trichomonas 

Significance. — This organism has been found intestinalis (Zenker), 
in cases of diarrhea, and seems to be able to 

irritate the intestinal wall but that it initiates an infection is doubtful; 
it more likely continues one already established. 




TRICHOMONAS VAGINALIS 

This form is rather smaller than the last, with an attenuated caudal 
end and a more blunt anterior portion, provided with three or four 
flagella; there is a lateral undulating membrane with six or seven short 
cilia. 

Significance. — The organism has been found in cases of vaginitis 
due to various causes, always in the presence of an acid secretion; when 
this is changed by menstruation or treatment it disappears. They do 
not seem to be transmissible to males. 

25 



386 



A TEXT-BOOK OF PATHOLOGY 



OTHER FORMS OF TRICHOMONAS 

Sternberg has found several forms in the mouth, and especially 
about the teeth. These have been termed Trichomonas flagellata, 
T. caudata, and T. elongata. A trichomonas closely related to Tricho- 
monas vaginalis has been found in gangrene of the lung and in putrid 
bronchitis. 

LAMBLIA INTESTINALIS 

This organism in its active state is irregularly pear shaped, and 
presents at its broad end a cup-shaped depression situated obliquely at 
one side (Figs. 148 and 149). On the anterior edge of the depression are 





Fig. 149. 

Figs. 148 and 149. — Lamblia intestinalis from the intestines of a mouse (Grassi and 

Sehewiakoff). 



attached two long cilia, and at one point of the posterior lip are two pairs 
of cilia. In the base of the depression are seen two vesicular structures 
(nuclei) united by a band. The protoplasm is finely granular and is sur- 
rounded by a delicate capsule. When free the organism is capable of 
rather rapid motion, but in the intestine it is attached to the epithelial 
cells by its cup-shaped depression. The organism exists in this form 
in the duodenum and jejunum. In the colon or other unfavorable situa- 
tions it forms oval encysted bodies showing the nuclei and cilia within. 

Significance. — Lamblia is a frequent parasite of the mouse, but has 
been found in the intestines of other animals, and occasionally in man. 
It has been found especially in chronic diarrheal conditions, and at 
times appears in the stools in immense numbers. No definite lesions 
have been found, and the pathogenicity of the germ is uncertain. 

The foregoing organisms seem able to exist as commensals in the 
intestines of animals but when infection arises, they aggravate it. In- 
creased peristalsis frequently appears as an effort of the gut to discharge 
the organisms. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



387 



TRYPANOSOMA 

Several varieties of trypanosomes have been recognized in animals, 
notably in horses and cattle. Among these, Trypanosoma evansi (Steel) 
has been found in the disease " surra" in horses and mules in India 
and Burmah; the T. brucei (Plimmer and Bradford) has been found in 
"nagana," a disease of horses and cattle in Central Africa; a form prob- 
ably identical with T. brucei has been found in u mal de Caderas," a 
disease similar to surra and nagana in Central South Africa and Brazil; 
T. equiperdum (Doflein) or T. rougeti (Laveran) in the disease of horses 
known as "dourine" in Algeria and other countries. A comparatively 
harmless variety (T. lewisi, Kent) occurs in a large proportion of wild 
rats. It has been the form on which many of the studies of trypano- 
somes have been made. A few other forms have been recognized. 

The trypanosome was discovered in the blood of a human patient 
by Dutton. The earlier reported cases of Nepvieu are open to some 
doubt. Dutton 's patient, an Englishman, had been along the Gambia 
River, and his symptoms were much the same as those met with in 




Fig. 150. — Trypanosoma gambiense: (1) From the blood; (2) from serosanguinolent 
fluid; (3) form showing rounded posterior extremity and granular protoplasm; (4) dividing 
form; X about 2000 (Laveran and Mesnil). 

animals from the same parasitic invasion. Great wasting and weakness, 
especially in the legs; irregular relapsing fever; edema, especially about 
the eyes; injection of the skin and conjunctivae; enlargement and 
tenderness of the spleen, and frequent pulse and respirations, were the 
principal symptoms. 

The name Trypanosoma gambiense (Dutton) has been proposed for 
the parasite of man (Fig. 150). 

The trypanosome is a minute, worm-like body, difficult to see in 
the fresh blood with a magnification of 300 diameters. One end of the 
parasite is drawn out into a flagellum; the other end is bluntly conical. 
An undulating membrane is attached along the body, which is short, 
thick, and granular. Near the posterior end is found a refractile spot 
(vacuole). The parasite moves forward or backward by means of the 
flagellum, but usually toward the direction of the flagellated end. Re- 
production occurs by longitudinal fission, and, in addition, it is thought, 
can occur by sexual reproduction. The organism readily dies in fresh 



388 



A TEXT-BOOK OF PATHOLOGY 



preparations. In the stained preparation it was found 18 to 25 ju in 
length and from 2 to 2.8 n in width. 

Novy and McNeal succeeded in cultivating trypanosomes in arti- 
ficial media composed of 1 part of nutrient agar and 2 parts of fresh 
defibrinated or laked rabbit or rat blood. The organisms retain their 
virulence in cultures for long periods of time. 

The trypanosome of man has been found pathogenic for certain 
monkeys and for dogs, cats, and rats. 

Transmission of the Disease.- — The transmission of the parasite is' 
effected by various blood-sucking flies. The Trypanosoma gambiense is 
conveyed by the Glossina palpalis; T. brucei, mainly by the tsetse fly, 
G. morsitans; T. lewisi, by fleas. The fly conveying the human para- 
site acts as a host, for it becomes infective three days after biting, and 
remains so four weeks, thus indicating that some form of metamorphosis 
takes place. 

The organism may exist in the blood of man for a long time without 
causing symptoms. Later it enters the cerebrospinal fluid and then 
causes the characteristic manifestations. As a rule, there is first irregu- 
lar fever, later pains and swelling of the extremities, and finally coma. 

The lesions discovered at autopsy consist of cerebrospinal meningeal 
congestion with increased fluid, and enlargement of the spleen and liver. 
The cerebrospinal fluid is in excess and cloudy, but not purulent. The 

arachnoid may be lifted from 
the convolutions and the pia 
has been found abnormally tight. 
The lymph-nodes are almost 
jgfc s universally enlarged and the 

/QP '^sJ0S^ - / spleen frequently shows a mye- 

0 ^6|fk loid transformation. 

Immunization of animals has 
jfP I been accomplished by repeated 

inoculations and immune sera of 
decided potency have been 
produced. 

Human trypanosomiasis is 
transmissible to monkeys. 

Leishmaniosis. — This term 
■ _. may be given to a group of three 

Fig. 151— Leishmania donovani. Flagellated diseases prevalent in Africa and 
forms from a culture. Wright's stain; x 1800 Southern Asia, known as "kala- 
January" fois). ° ffice * Surgeon Genera1 ' azar" or "dumdum fever,'; "in- 
fantile kala-azar," and " oriental 
sore" or " Aleppo button." The causative organism is a near relative 
of the trypanosomes, among the Flagellata. The symptoms of the 
first two are moderate anemia and fever, associated with splenomegaly. 
The spleen shows little microscopical change aside from hyperplasia. 
The prognosis is grave. Oriental sore is characterized by the appearance 
on skin surfaces of spreading suppurating and ulcerating granulomata. 
These lesions tend to heal and leave disfiguring scars. 

The causative organism is known as Leishmania donovani, after the 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 389 

men who discovered and described it. It varies but slightly in the 
three clinical forms above, only differing in size and appearance upon 
cultivation. It may be grown upon the medium described for trypano- 
somes. In the body the parasite exists as an intracellular round or 
oval (2.5 by 3.5 ju) mass containing two more deeply staining large 
granules. The larger, or nucleus, lies excentrically, parallel to the 
long axis of the parasite. The smaller granule is probably the blepharo- 
blast. Vacuoles may be present. The parasites stain palely, while 
the granules are dark. They lie within lymphocytes and endothelial 
cells. They do not appear in any numbers in the circulating blood, 
but may be found in lymph-tissue and marrow (Fig. 151). 

The manner of transmission is not known, but insects and bedbugs 
are suspected. 

Histoplasmosis is a condition characterized by anemia, prostration, 
splenomegaly, fever, and emaciation, caused by the Histoplasma capsu- 
latum (Darling), a flagellate related to the trypanosomes. The organs 
may occasion spreading granulomata and the intestines show ulcera- 
tion. The organism is intracellular, has an irregular oval nucleus, 
vacuoles, and a wide capsule. The organism has not been cultivated. 
The disease was found in the Panama Canal Zone. 

Hemosporidia 
THE PARASITES OF MALARIA 

The organisms which are now recognized as the cause of malaria 
belong to the protozoa. Most authors regard them as Sporozoa, sub- 
order Hemosporidia. They are found in the blood and the vascular 
channels of the various organs, deriving their nourishment, for the 
most part, directly from the blood-corpuscles. 

Malaria, as the name implies, was ascribed by the ancients to a 
miasm arising from wet ground, a view that held in many quarters until 
the end of the nineteenth century despite plenty of observations to 
throw doubt upon it. In 1880 Laveran observed the parasites in the 
blood corpuscles and in 1884 made the suggestion that mosquitoes had 
something to do with the causation of the disease but it was not until 
1895 that Manson and Ross succeeded in convicting these pests with 
the principal role in the transmission. Thus was explained the asso- 
ciation of attacks with low illy drained ground and recent excavations 
and the inability of investigators to transmit the infection by contact. 
Other animals notably birds are also affected with hemosporidia trans- 
mitted by mosquitoes. 

Three distinct species have been identified in man: the organism 
of tertian fever (Plasmodium vivax, Figs. 152-155), that of quartan 
fever (P. malarice), and that of estivo-autumnal fever (P. falciparum or 
Laverania malarice) . Each of these has a double life cycle, one within 
the human host, the other in the body of the mosquito. In the human 
circulation, spleen, or elsewhere asexual reproduction (schizogony) of 
parasite occurs until it has exhausted its reproductive power or the 
antagonistic bodies have destroyed it, while in the mosquito sexual 
reproduction (sporogony) occurs by conjugation. 



390 



A TEXT-BOOK OF PATHOLOGY 



Plasmodium Vivax. — The C3 r cle of development in the blood of man 
begins with a small hyaline spherule (schizoni) about 2 p in diameter 
which is attached to and later within a red corpuscle. Soon pigment 
particles appear within the parasite, being derived from altered hemo- 




v 



0* 



Fig. 152. — Plasmodium vivax. Falf- 
grown parasite. Wright's stain; X 1500 
(Craig, Bulletin No. 6, War Depart- 
ment) . 



Fig. 153. — Plasmodium malariae. 
Half-grown parasite, the so-called band 
form. Wright's stain; X 1800 (Craig, 
Bulletin No. 6, War Department). 



globin. The pigment particles are more or less actively motile, due to 
currents in the protoplasm. Later the body increases in size and the 
corpuscle in which it is contained swells and becomes paler. Finally, 
the sphere increases to perhaps twice the size of a normal corpuscle. In 
all stages ameboid changes in the shape of the organism may be observed, 




W 



Fig. 154. — Plasmodium vivax. 
Fully developed macrogametocyte. 
Wright's stain; X 1800 (Bulletin No. 1, 
Medical Department U. S. Army, 1913.) 



Fig. 155. — Plasmodium vivax. 
Fully developed microgametocyte. 
Wright's stain; X 1800 (Bulletin No. 1, 
Medical Department U. S. Army, 1913). 



but become less and less marked as the Plasmodium enlarges. In the 
spleen, and to a less extent in the circulating blood, division of the para- 
site may be observed about the time of the expected paroxysm of the 
disease. The pigment collects in the center, the organism forms a 
rosette and then divides into fifteen or twenty rounded segments or 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 391 

merozoites. These escape from the destroyed red corpuscle and are then 
ready to attack a new corpuscle and begin the same cycle. 

In the earlier stages the hyaline body appears as a light area on an 
otherwise normal red corpuscle; somewhat later its rounded shape sug- 
gests a ring and the term " ring-bodies " is given. This is conspicuous 
in preparations stained with a chromatin stain such as in the Nocht- 
Romanowsky method. The body of the parasite is blue and at one 
point in the periphery may be seen red chromatin matter, thus suggest- 
ing a signet ring. Before segmentation the chromatin collects in the 
center and eventually divides, a portion being found in each of the 
merozoites. The cycle of development of this form occupies about forty- 
eight hours. 

Plasmodium Malarial. — The organism of quartan fever differs from 
the tertian in that it is less pigmented and the pigment is usually coarser, 
more characteristically arranged at the periphery of the parasite, and 
usually motionless. The segmentation is more regular, forming a wheel- 
like figure with nine to twelve segments which form the sporules or 
merozoites. The segmentation occurs only in the circulating blood and 
the cycle occupies seventy-two hours. The corpuscle containing the 
organism does not enlarge nor grow pale as in the case of the tertian 
form, but instead presents a greenish appearance. 

Plasmodium Falciparum or Laverania Malar ice, — The organism of 
estivo-autumnal fever is believed by Italian and tropical investigators 
to occur in two forms: a tertian and quotidian, which have certain dis- 
tinguishing features. The organism is characterized by its tendency to 
develop marked signet-ring forms, by its relatively small size, and by its 
fine granulation and highly refractive protoplasm.' Segmentation in to 
7 to 10 parts occurs in forty-eight hours and takes place mainly in the 
spleen, bone-marrow, liver, and capillaries of the brain, the schizonts 
having disappeared from the blood usually well before the time mentioned. 

Sporogony. — A certain number of the plasmodia of any one of the 
three varieties, when of mature size, instead of undergoing segmentation 
become differentiated as male and female forms or gametocytes. In the 
tertian and quartan varieties the male form, or microgametocyte, is a 
rounded body with centrally placed nucleus, having an abundance of 
chromatin and a considerable amount of actively motile and diffused 
pigment matter (Fig. 155). The macrogametocyte, or female form, has 
an excentrically placed nucleus with less chromatin and coarser pigment 
arranged in clumps about the periphery of the organism (Fig. 154). In 
the case of the estivo-autumnal parasite the gametocytes first appear as 
oval bodies within the red corpuscles, but soon they assume the well- 
known form of crescents, which even when quite mature may present on 
the concave border remains of the red cell in which they developed. The 
crescent contains rod-shaped pigment in a cluster either at its center or 
one pole, and a male and female form can be distinguished. These 
sexual forms (gametocytes) of malarial plasmodia are less abundant in 
the earlier stages of infection than later when schizogony or asexual 
division becomes less active. 

When blood is drawn and kept for a time under a cover-glass further 
changes take place in the gametocytes, which are similar to those which 



392 



A TEXT-BOOK OF PATHOLOGY 



occur in the body of the mosquito. The microgametocyte presents 
active movements of its pigment and finally a protrusion of several 
flagella which extend to two or three times the diameter of the cell. 
These flagella, or microgametes, the male element concerned in the process 
of fertilization, become detached from the cell and penetrate the female 
organism, macrogametocyte, after the latter has undergone a prepara- 
tory change (certain nuclear extrusions) and has thus been converted 
into a macrogamete. Further stages in the sexual cycle of reproduction 
occur only in the body of the mosquito. 

Parthenogenesis. — It has been claimed by Schaudinn, but denied by 
others, that parthenogenesis of the macrogametocyte may restore to the 
blood a new generation of merozoites when schizogony is becoming 
feeble. According to this view, the gametocytes represent resistive 
forms which are able to withstand unfavorable conditions developed in 
the course of an infection (antibody formation?). The female, or macro- 
gametocyte, is particularly resistive, may remain in the blood after 
other forms have disappeared, and may then by a process of partheno- 
genetic segmentation produce a new generation of merozoites. This 
theory would explain certain cases of late reappearance of infection after 
apparent recovery. 

Bass has lately succeeded in cultivating the asexual cycles in the 
species of vivax and falciparum by using equal parts of 0.5 per cent, 
glucose bouillon and blood, or Locke's fluid minus calcium chlorid plus 
ascitic fluid. The blood is defibrinated in flat-bottom tubes of such 
size that the clear fluid layer above the cells is at least J£ inch in height. 
The parasites grow in the upper layer of red cells and can be transferred 
by a pipet to fresh tubes of uninjured cells for a secondary growth. 
Leukocytes and serum are prejudicial to the growth of the Plasmodium; 
the former by phagocytosis, the latter by lytic effects. 

The Relations of the Mosquito to Malaria. — It has been positively 
demonstrated that when certain mosquitoes of the genus Anopheles are 
allowed to feed upon malarial patients and later upon normal individuals, 
the latter acquire the disease. Also, it has been shown that susceptible 
persons may live in the most malarious districts without acquiring the 
disease, provided they are carefully screened from mosquitoes. Some 
of the earlier investigations in this direction failed because specimens of 
Culex and other genera (not Anopheles) were used. The Anopheles 
claviger, maculipennis, or quadrimaculata and others of this genus alone 
seem capable of conveying the disease. When the mosquito takes the 
blood of the malarial patient into its stomach (midintestine), flagellate 
forms (microgametocytes) are developed, and the flagella (microgametes), 
each containing some part of the nuclear substance of the parent cell, 
are discharged, and, moving toward other of the parasites which do not 
form flagella (macrogametes) , fertilize these by penetration. The fertil- 
ized parasites then invade the intestinal walls, entering between the epi- 
thelia, and lodge in the surrounding tissues, where they segment and 
develop a distinct capsule. The cystic structures so formed (oocysts) 
contain numerous minute rods or sporozoites that have resulted from 
the segmentation of the parasite. The oocysts project into the ccelom 
cavity of the mosquito and eventually rupture into this, whence the 



PLATE 3 




4fe 



// /? ^ /* 



r r LI 



/5 /T" 



18 19 20 21 22 



23 24- 25 26 27 

* i 

4 i< < 



Various forms of malarial parasites (Thayer and Hewetson): Figs. 1 to 10 inclusive, 
tertian organisms; Figs. 11 to 17 inclusive, quartan organisms; Figs. 18 to 27 inclusive, 
estivo-autumnal organisms. 

Fig. 1. — Young hyaline form; 2, hyaline form with beginning pigmentation; 3, pig- 
mented form; 4, full-grown pigmented form; 5, 6, 7, 8, segmenting forms; 9, extracellular 
pigmented form; 10, flagellate form. 

Fig. 11. — Young hyaline form; 12, 13, pigmented forms; 14, fully developed pig- 
mented form; 15, 16, segmenting forms; 17, flagellate form. 

Figs. 18, 19, 20. — Ring-like and cross-like hyaline forms; 21, 22, pigmented forms; 
23, 24, segmenting forms; 25, 26, 27, crescents. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 393 

sporozoites, discharged into it, are carried to different parts of the body 
and eventually to the salivary glands, from which they are introduced 
into any person subsequently stung by the insect. In this manner the 
extracorporeal cycle of development of the organism is completed and 
the perpetuation of the disease provided for. 

The recognition of the relation of the mosquito to malaria explains 
certain hitherto obscure facts regarding the conditions that favor the 
development of the disease. This knowledge has also led to the intro- 
duction of sanitary measures that have proved extremely useful. 

Pathological Anatomy. — The most important fact in malarial 
infection is the destruction that it occasions in the blood. Rapid anemia 
with liberation of the hemoglobin (hemoglobinemia) and the appearance 
of granular pigment in the blood are among the results. The pigment 
accumulates in the spleen, liver, bone-marrow, and in other situations. 
Extreme disorganization of the blood may occasion hemoglobinuria and 
widespread pigmentation. Congestive enlargement of the spleen, and, 
after long-continued attacks, cirrhotic changes in that organ, may be 
observed. Thrombi of the capillaries and arterioles are not rare, and to 
these, in part at least, are due the focal necroses observed in the liver 
and elsewhere. In the bone marrow there is a moderate amount of 
mononuclear increase but more characteristically a large number of 
phagocytic cells like endothelia, containing plasmodia or pigment gran- 
ules. Cytologically these large mononuclear phagocytes are the out- 
standing feature of tissue sections, originating mostly from vascular 
endothelia but also from sinus cells in lymph nodes and Kupffer cells in 
the liver. They frequently contain plasmodial remnants and always 
pigment granules, sometimes so closely packed that the nucleus is 
obscured; the cells may be so thick in certain tissues as to give a dark 
appearance to them (bluish black spleen). 

Pathological Physiology. — -The curiously paroxysmal seizures of 
malaria are probably the result of the liberation of toxic substances at 
the time of segmentation of the hematozoon. The periodicity depends 
upon the cycle of development of the organism. A single group of 
tertian organisms causes a tertian fever (a paroxysm every other day) . 
Infection with two groups of tertian organisms, maturing on alternate 
days, produces a quotidian fever (a paroxysm every day). One group 
of quartan organisms causes quartan fever (a paroxysm every third day) ; 
three groups (maturing on successive days) cause quotidian fever. The 
febrile course in estivo-autumnal infection is more irregular, and this is 
explained by the discovery of organisms of various ages in the blood. 
Thus there results a constant succession of maturations and segmenta- 
tions with less distinct periodicity, because the intervals which occur in 
tertian and quartan infection are wanting. 

The anemia is usually ascribed to the continued attacks of the para- 
sites upon successive numbers of erythrocytes; some late observations 
lay the hemolysis to the circulation of free hematin, which substance, 
if injected into rabbits, produces a blood-picture like that seen in human 
malaria. 

Texas Fever of Cattle. — This disease is of interest in connection with 
malaria because of the relationship of the parasitic cause. The organism 



394 



A TEXT-BOOK OF PATHOLOGY 



is a small, actively ameboid body which occupies the red blood-cor- 
puscles. Frequently it occurs in pairs in the corpuscles, and the name 
Pirosoma bigeminum was given to it on this account. Texas fever is 
characterized by acute fever and frequently by hemiglobinuria. The 
spleen is enlarged and hemorrhages are observed in various organs. 
When the blood of a diseased animal is injected into a healthy one, the 
latter acquires the disease. Transmission has been traced to the cattle 
tick {Ixodes bovis). The mother tick, after its detachment from the in- 
fected animal on which it has fed, transmits the infectious agent to its 
larvae through the ova. The young ticks then convey the infection to 
healthy cattle. 

Sporozoa in Birds and Cold-blooded Animals. — Many blood para- 
sites have been studied in birds, reptiles, and other cold-blooded animals. 
In birds two species, Hcemoproteus danilewskyi and Halteridium danilew- 
skyi, have been closely studied, thus throwing much light on the life 
history of the malarial organisms. 

Coccidia 

COCCIDIUM CUNICULI 

Description. — The coccidia are small bodies from 30 to 40 m in 
length and from 15 to 20 n in width, having a delicate outer coating, 
and within this a tough, double-contoured capsule. The body is filled 
with granular material, which is not rarely aggregated in the center. 
Outside the body sporulation takes place. The granular protoplasm 
divides into four rounded capsulated spores, each containing a granular 




Fig. 156. — Coccidium oviforme, showing method of reproduction. 



resting body lying in the concavity between two sickle-shaped daughter- 
spores. Sometimes endogenous sporulation is said to occur, the para- 
site simply breaking up into a large number of sickle-shaped bodies. 
The term psorospermice is applied to the rounded spores found in the 
coccidium (Fig. 156). 

The coccidium can also pass through a sexual reproduction (sporog- 
ony) with a cycle comparable to that of malarial parasites in the devel- 
opment of young and adult male and female forms. 

Occurrence and Pathogenesis. — The coccidium is a frequent para- 
site of rabbits and certain other animals. It leads to the formation of 
yellowish nodules in the liver. It is an intracellular parasite, first in- 
vading the cells of the biliary passages and afterward the surrounding 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



395 



hepatic cells as well (Fig. 157). Less frequently it occurs in the intes- 
tinal tract, giving rise to nodular thickenings or ulcerations. 

The parasite escapes from the body in the stools and then undergoes 
sporulation. Other animals are probably infected by ingestion of the 
spores or sporulating coccidia. Occasionally the disease decimates rab- 
bits or guinea-pigs kept in confinement. The animals become languid, 
lose their appetite, emaciate, and have fever. Later they surfer from 
convulsions, stupor or coma, and die in this condition. 




Fig. 157.— Coccidia in the wall of the bile-duct. The cut shows in the center active pro- 
liferation of the wall of the duct, with numerous ovoid coccidia massed in the tissue. 

A few cases of coccidial disease of the liver have been observed in 
man. The lesions present themselves as cystic nodules springing from 
the bile-ducts, or less commonly as a diffuse involvement of the liver 
with cirrhosis and causing jaundice. Coccidial lesions of the intestines 
have also been discovered in man, and less commonly invasion of the 
heart, of the kidneys, and other parts. 

The close association of the organism with the lesions, and the num- 
ber of organisms discovered in the tissues, justify the belief that it is the 
specific cause of the lesions. 

The coccidium of the intestinal tract is generally smaller and the 
sporulation more rapid than that of the hepatic form. It was, therefore, 
supposed by Leuckart to be a special variety, and has been called Cocci- 
dium perforans or C. hominis. More recently this has been regarded as 
identical with the ordinary form. 

Isospora bigeminal (Stiles). — This variety has been found in dogs, 
cats, pole-cats, and man. The cyst divides into two parts and then forms 
four spores. 

Eimeria Hominis. — Eimeria is characterized by the formation in 
each adult parasite of a single spore containing an indefinite number of 
sporozoites. The Eimeria hominis was discovered in the purulent exu- 
date of a case of pleurisy. The spores were of large size and contained 
from ten to twenty sporozoites, accompanied by a protoplasmic rem- 



396 



A TEXT-BOOK OF PATHOLOGY 



nant. The exact origin of the organisms in this case was not determined. 
Somewhat similar organisms were found by Virchow in a tumor of the 
liver, and by Severi in the lung. 

SARCOSPORIDIA 

The sarcosporidia, also called "K,aineyV and " Miescher's tubes," 
are met with in a number of mammals. The organism is composed of a 
protoplasmic mass covered with a capsule, and forming at the stage of 
maturity a large number of sickle-shaped or falciform sporozoites. The 
organisms usually occur in muscles, either within or between the muscle 
bundles, and are, therefore, elongated or tubular in shape. In connec- 
tive tissues the organism may be rounded and sometimes grows to the 
size of a small cherry. Several varieties have been described, and a few 
observations have been made in man, where the heart muscle is often 
affected. 



Infusoria 

BALANTIDIUM COLI 

Balantidium or Paramecium coli is a rounded body from 0.07 to 
0.1 mm. in length and slightly less in breadth (Fig. 158). It is sur- 
rounded by a coat of cilia closely set. There is an oral 
aperture at one end and an anal opening at the other. 
The substance of the parasite is granular, and contains 
a bean-shaped nucleus, within which is a round nucleolus 
and two contractile vacuoles, besides various foreign 
matters. The parasite possesses ameboid motion. 
Encysted forms with a thickened capsule have been 
described. 

Significance.- — The hog is the natural host of this 
parasite. Man is probably infected through drinking- 

Balantidium coli . ~ , r , , „. T * • * j 

(Maimsten). water or contaminated food-stuns. It is tound par- 
ticularly in the northern countries of Europe, and occurs 
in cases of diarrhea, principally involving the large intestine. The parasite 
penetrates between the epithelial cells by its ameboid motion. Chronic 
catarrhal inflammation and dysenteric lesions have been described. The 
lesions are chiefly purulent, necrotic, and ulcerative in the colon. The 
parasite may be found mixed with the degenerative mass. Occasionally 
liver abscess is seen and a penetration to the blood-vessels has been ob- 
served. It is possible for it to penetrate the lymph-nodes of the intestinal 
wall or as far as the mesenteric glands. The organism is probably irritat- 
ing, but whether pathogenic or not is unknown. Epidemics have been 
observed in monkeys, the manifestation being prolonged diarrhea. 

Balantidium ' Minutum. — This species resembles the Balantidium coli, but is 
smaller (40 /j, long), has a more prominent mouth, and but one vacuole. It has been 
found in association with Strongyloides, Ankylostoma, and Amoeba. Its significance 
is uncertain. 

ANIMAL PARASITES AND MOLLUSCUM CONTAGIOSUM 
Definition. — Molluscum or epithelioma contagiosum is an infectious 
disease of the skin marked by the appearance of white and pink papules. 




ANIMAL PARASITES AND DISEASES CAUSED BY THEM 397 

Etiology. — The cause of this disease is, no doubt, a micro-organism 
of some sort. Its contagiousness is evidenced by the occurrence of epi- 
demics in houses or asylums, by the occurrence of accidental inocula- 
tions, and by direct experiments. The incubation period seems to be a 
long one — sometimes extending to several months. The lesions have 
been found to contain small bodies whose resemblance to coccidia was 
long ago pointed out by Virchow. It is uncertain whether these are 
really parasites or epithelial degenerations. Some authors are positive 
regarding the parasitic nature of the bodies; others are equally con- 
vinced of their non-parasitic character. The most ably defended theory 
for the parasitic nature of the virus ascribes it to an organism called 
Strongyloplasma hominis. 

It has been shown that the virus is filterable, and many consider 
it should be placed among the Chlamydozoa. The large pale body, 
with the later appearance of internal structure, seen only by appropriate 
staining, strongly supports this view. 

Appearances. — The disease occurs as single or, more frequently, 
multiple papules,, at first quite small, but later becoming nodules of con- 
siderable size. In the larger a central depression or umbilication is seen, 
and on pressure cheesy matter may be expressed from this. After reach- 
ing about 3 or 4 mm. in diameter the papules remain stationary, or 
undergo softening and suppuration. In exceptional cases the tumor 
may reach the size of a small orange. 

Seats. — This disease occurs on the face, neck, chest, genitals, or 
sometimes scattered over the whole body, sparing only the palms and 
soles. The lesions have occasionally been found on the mucous 
membranes. 

Structure. — 'Microscopically, the lesions of this disease are found to 
consist of epithelial proliferations having a somewhat acinous arrange- 
ment, a hair-follicle occupying the center of each group of cells The 
interior of the nodules is filled with soft, cheesy matter which may be 
expressed. The epithelial cells are arranged in several layers, the upper 
being normal cells with large nuclei, the deeper layers showing, besides 
the nucleus, small droplets, Or rounded spherules, the so-called molluscum 
bodies. These bodies grow in size and may be so large as to fill the cell, 
pushing the protoplasm and nucleus to one side. In this process the 
cell wall and protoplasm become horny, and practically the entire body 
consists of the enlarged molluscum corpuscle. Certain granulations 
and more or less definite segmentations within theses bodies have been 
described as sporulating conditions. (See Skin.) 

Vermes 

Trematodes, or Fluke- worms 

The fluke-worms are usually flattened organisms, somewhat tongue 
shaped, and provided with powerful suckers and occasionally with 
hooklets. The intestinal canal begins in the oral orifice anteriorly, and 
the excretory openings may also be there but a few genera have a single 
posterior outlet. Reproduction may take place directly or by the for- 
mation of an intermediate organism which is parasitic to certain lower 



398 



A TEXT-BOOK OF PATHOLOGY 



animals. In this stage they are actively motile, swimming about in 
water, and are known as the cercarise. Nearly all forms are hermaphro- 
ditic. Their action is irritative and obstructive. In the following pages 
there are given several of the principal species known to have caused 
some form of disease in man but the list is by no means complete since 
full discussion would require more space than can be allotted in this work; 
the reader is therefore referred to systems on parasitology for extended 
reading. 

FASCIOLA HEPATICA OR DISTOMUM HEPATICUM 

The Fasciola hepatica, or liver-fluke, is from 15 to 35 mm. in length 
and 6 to 20 mm. in breadth; it is pointed at either end, and anteriorly 




Fig. 159. — The common liver-fluke Fig. 160. — Ventral view of a compressed 

(Fasciola hepatica) , enlarged to show the specimen of a lung-fluke (P. wfestermanii) from a 
anatomical characters (after Stiles). hog; greatly enlarged (after Stiles and Hassall). 

is provided with two suckers, one at the head and one upon the ventral 
surface, somewhat posterior to the first (Fig. 159). The genital pore lies 
between the two suckers. The eggs are oval in shape, 0.14 to 0.15 mm. 
in length, and provided with a lid at one pole. 

The adult organism occupies the biliary ducts and is a frequent 
parasite of sheep. It is occasionally met with in man, usually occurring 
in considerable numbers. It gives rise to obstruction of the biliary pas- 
sages and consequent enlargement, congestion, and later degeneration 
of the liver. The gall-ducts above the point of obstruction have 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



399 



sometimes been found considerably dilated or cystic. Clinically, ascites 
and jaundice have been found, with gastro-intestinal symptoms and 
fasciola eggs in the stools. 

OPISTHORCHIS FELINEUS 

This form varies in size with the degree of contraction, but is usually 
8 to 11 mm. in length and 1.5 to 2 mm. in breadth. The two suckers are 
far apart, and the genital pore is just in front of the ventral sucker. The 
eggs are oval, operculated, measuring 0.03 mm. in length and 0.01 mm. 
in breadth, and contain a ciliated embryo when deposited. This parasite 
inhabits the gall-bladder and bile-ducts of the domestic cat in particular, 
but is also found in the dog, fox, and man. It has been observed in 
France, Germany, Russia, Holland, Italy, and Japan. 

CLONORCHIS SINENSIS 

This parasite resembles the Opisthorchis felineus. The length is 
10 to 14 mm.; the breadth, 2.4 to 3.9 mm. The eggs are oval with 
a sharply denned operculum at the pointed pole; they measure 0.030 
mm. in length and 0.017 mm. in breadth. This parasite inhabits the 
bile-ducts and gall-bladder of domestic dogs and cats as well as of 
human subjects. It is found frequently in Japan, also in China and 
India. 

SCHISTOSOMUM HAEMATOBIUM OR DISTOMUM HAEMATOBIUM 

This organism, sometimes called Bilharzia, occurs in sexually dis- 
tinct forms, the male and female, however, occurring together. The 
male is 12 to 14 mm. in length and 1 mm. thick, and the body back of the 
large ventral sucker is somewhat flattened and curved ventralward to 
form a groove, in which the female is attached (Fig. 161). The latter is 




Fig. 161. — Schistosomum haematobium, with eggs (von Jaksch). 



16 to 18 mm. long, and 0.13 mm. thick. The eggs are 0.135 to 0.180 
mm. long and 0.055 to 0.060 mm. broad, not operculated, and having a 
spine at one end or at the side of one end. The adult parasite occupies 
the portal vein and the veins of the spleen, mesentery, and the plexuses of 
the bladder and rectum. The eggs of the organism may be found in any 
of the organs, notably in the- liver, in the intestinal walls, and in the 
mucous membranes of the urinary passages. They probably occupy the 
vascular system ordinarily, but cause rupture of the walls of the vessels 
and thus escape into the tissues. 

The pathological changes caused by this parasite and included in 
the term " bilharziasis " are more strikingly seen in the ureters and blad- 
der in acute cases. Hyperemic spots or small hemorrhages may be seen 
in the mucous membrane, and the surface is covered with blood-stained 



400 



A TEXT-BOOK OF PATHOLOGY 



mucous containing the eggs. In cases of longer standing roughness of the 
mucous membranes and usually small ecchymotic elevations or out- 
growths, suggesting papillomata, are observed (Fig. 162). Section 
through these shows that they consist of proliferated cells with enlarged 
blood-vessels, from which the adult worm may be removed. The 
tissues surrounding the vessels may contain eggs in enormous numbers. 
The mucous membrane is frequently covered with a calcareous deposit 
composed of urate and oxalate of sodium, and the 
excrescences may be converted into calcified polyps. 
Among the final results may be cicatricial strictures 
of the ureter, pyelitis, and distention of the pelvis of 
the kidney, with atrophy of the kidney substance. 
Similar pathological processes may be found in the 
rectum. When the portal vein is occupied the eggs 
of the Bilharzia may be abundant in the liver sub- 
stance. Schistosomum hcematobium is a parasite oc- 
curring with enormous frequency in northern Africa 
and neighboring countries. It is comparatively rare 
in other parts of the world. A closely related variety 
causing essentially -the same lesions is Sch. mansoni. 

SCHISTOSOMUM JAPONICUM 

Schistosomum japonicum, or S. cattoi, has recently 
/U been discovered in eastern Asia and Japan. This 

parasite inhabits the arterial side of the portal system. 
It is somewhat smaller than Schistosomum hcematobium, 
and the male is distinguished by his non-tuberculated 
integument. The ovum has no spine, is regularly 
oval, perfectly smooth, and with a much thinner shell. 
It resembles closely the ovum of Ankylostoma duodenale. 
The ova are deposited in the mucosa and submucosa 
of the large and small intestine^ especially the former. From here they 
escape with the feces. No more is known of the life-history from this 
point than is the case with the Schistosomum hcematobium. It causes 
a peculiar kind of chronic enteritis and anemia, associated with enlarge- 
ment of the spleen and liver, terminating in a fatal cachexia. Cats 
are susceptible to this parasite as well as man. 




Fig. 162— Papil- 
lary thickening of the 
mucous membrane of 
the bladder, showing 
schistosomum eggs in 
situ (Mosler and 
Peiper) . 



PARAGONIMUS RINGERI 

This organism is from 8 to 10 mm. in length and from 5 to 6 mm. in 
breadth. The eggs are brownish, and from 0.08 to 0.1 mm. in length. 
It is claimed by Nakagawa that, after reaching the jejunum, the parasite 
penetrates the gut wall and the diaphragm whence they gain the lung. 
Penetration to other organs may occur but only in the pulmonary tissue 
do they gain full development. The worm occurs in the lungs, occupying 
excavated spaces, usually near the periphery of the organ. These cavities 
contain reddish or quite hemorrhagic mucopurulent liquid and abundant 
eggs. The cavities are in communication with the bronchi, and clinically 
the disease is marked by cough and hemorrhagic expectoration or even 
repeated hemoptysis. The parasites themselves are rarely coughed up. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



401 



The small tumors or burrows have also been found in the scrotum, liver, 
and brain. In the brain they may give rise to grave nervous symptoms, 
often simulating those of intracranial tumor. This parasite occurs very 
frequently in Japan, China, and Corea, and has been observed several 
times in this country. Related varieties are Par. westermanii and Par. 
kellicotti. 

OTHER FLUKE-WORMS 

Among other forms of fluke-worms of less importance are Fasciolopsis 
buskii, met with a few times in the intestine; Agamodistomum ophthalmo- 
bium, found in the lens of the eye; Parapisthorcis caninus, occurring in the 
liver; and the Monostomulum lentis, occurring in the eye. The Gastro- 
discus hominis occurs in the intestinal tract. Fasciolopsis rathouisi is a 
fluke found in the intestinal canal of Asiatics. Clonorchis endemicus occurs 
in central Japan, appearing in the intestinal tract after using infected fish. 

Cestodes, or Tapeworms 

General Biology. — The life-history of the different forms of tape- 
worms is much the same. They have two states of existence, the larval, 
which is generally found in one species of animals (the intermediary 
host), and the adult, usually occurring in another species (the host). 
It. is supposed that in the case of one or two tapeworms an inter- 
mediary host is unnecessary, but this is doubtful. The adult worm, or 
tapeworm (strobile), occupies the intestinal tract of man or the lower 
(vertebrate) animals. It consists of a head (scolex), by which the worm 
fastens itself to the mucous surface; and after the head, a neck of greater 
or less size and length, and a body consisting of separate links or pro- 
glottides. The latter represent complete organisms, containing a com- 
plicated genital apparatus, hermaphroditic in nature, which produces 
numerous eggs. The eggs are partly discharged from the segments in 
the intestinal tract through a genital pore, but especially escape into 
the outer world when the ripe segments are separated from the body 
of the worm, are discharged from the bowel, and subsequently rupture 
and scatter the contained ova (Fig. 163). The egg or ovum encloses an 
immature larval organism, which, when received into a suitable inter- 
mediary host, penetrates the walls of the stomach or intestine and 
finds its way to the muscles or organs, where it embeds itself and forms 
the well-known measles (Figs. 163 and 164). These are seen with 
the naked eye as small cyst-like bodies lying between the muscle-fibers. 
They contain a scolex or head, like that of the adult worm, inverted into 
a sac filled with clear, watery liquid. When the measles or cysticerci 
occur in hollow cavities, such as the ventricles of the brain, they may 
reach considerable size. They differ somewhat in different forms . of 
tapeworm, as will be described in connection with the individual species. 
When flesh infested with larval tapeworms is eaten by man or some 
suitable animal, the cysts are dissolved and the scolex fastens itself 
upon the mucous membrane of the intestine. The body of the worm 
is then slowly or rapidly formed. 

26 



402 



A TEXT-BOOK OF PATHOLOGY 



Man is the host of tapeworms of adult or of larval type, most fre- 
quently the former. In one case, the Tcenia echinococcus, only the 
larval worm occurs in the human body, in the form of hydatid cysts. 




l F2 3 

Fig. 163. — Segments of (1) Taenia saginata; (2) Bothriocephalus latus; and (3) Taenia 
solium, showing arrangement of uterus. 



Pathological Physiology. — Adult tapeworms may exist in the intes- 
tines of man without causing disturbances of any kind. Frequently, 
however, digestive disturbances and pain and various reflex manifes- 




Fig. 164. — Eggs of various worms found in the alimentary canal of man: a, Ascaris 
lumbricoides; b, c, Oxyuris vermicularis; r>, Trichocephalus trichiurus; e, Ankylostomum 
duodenale; f, Fasciola hepatica; g, Dicrocoalium lanceatum; h, Taenia solium; 1, Taenia 
saginata; k, Dibothriocephalus latus; X 400. 

tations arise. These may be caused by the action of the worm as a 
simple foreign body, or may result from poisonous agents generated by 
the worm in its normal life, or as a consequence of death and degenera- 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



403 



tion of the segments. When there are many worms (as in the case 
of Hymenolepis nana) the disturbances of digestion may be largely 
mechanical; under similar circumstances, or when a single worm be- 
comes coiled and forms a mass, intestinal obstruction may be occasioned. 
In the case of Dibothriocephalus latus poisonous substances are un- 
doubtedly produced, and to these must be ascribed the severe forms of 
anemia caused by this worm. The toxic substance is produced by the 
worm and is within its body, but can be absorbed by the intestine. 
That such occurs is indicated by the precipitation reaction between 
blood of patients and extracts from the worm. The poison is a hemo- 
lytic lipoid body. Other tapeworms rarely occasion anemia, and never 
the pernicious type just referred to. 

TiENIA SOLIUM 

This form, sometimes called the pork tapeworm, occurs in the adult 
state in man as a worm 2 or 3 meters in length ; and in the hog or rarely 
in man in its larval condition. The head is about the size of a pin-head 
and very dark. Anteriorly it has a rostellum armed with a double row of 
from twenty-two to thirty-two hooklets. At the sides of the head are 
four suckers (Fig. 165). Attached to the head 
is a neck of thread-like appearance, which termi- 
nates at once in the fairly developed segments 
of the anterior part of the body. The segments 
at first are broad and short, but become longer 
in proportion to the breadth toward the posterior 
end. The sexually mature segments are found 
at the middle and the posterior end of the worm. 
They contain a uterus consisting of a median 
tube and six to twelve lateral branches (see 
Fig. 163, 3). The genital pore is found at one 
side of the segment, irregularly alternating in 
successive proglottides. The eggs, which may 
be squeezed from the segments or obtained free 

in the feces, are either oval or spherical, from Taenia solium (Mosier and 
0.030 to 0.035 mm. in diameter, and consist of a Peiper). 
peripheral striated zone and a central granular 

portion, showing indistinctly six lines representing hooklets (see Fig. 163). 
Groups of segments may be discharged from the bowel from time to 
time, but this is not frequent; the discharge of single segments is quite 
unusual. The proglottides have independent movement, and may 
sometimes be seen to move about upon the bed-clothes. 

The cysticercus stage which gives rise to the Tcenia solium lives nor- 
mally in the intramuscular connective tissue and organs of the domestic 
pig, but it is known to exist also in a few other mammals as well as in 
man. 

The Larval State in Man. — When the ova are taken into the stom- 
ach the shell is digested and the embryo with its six hooklets is set free. 
This penetrates the wall of the stomach or intestine, and in some un- 
certain manner reaches the muscles or organs, where it effects a lodg- 
ment. The hooklets are discarded and a little cyst containing clear 




Fig. 16 5. — Head of 



404 



A TEXT-BOOK OF PATHOLOGY 



liquid is formed, and at one point may be found a bud-like projection 
into the sac. This develops a scolex or head, which eventually becomes 
identical with the head of the fully formed worm. The cyst may be 
surrounded by a wall of reactive connective tissue. The duration of 
this process of formation of this so called cysticercus cellulosce varies 
somewhat (five to ten or twelve weeks). The size of the cysts in the 
muscles varies from minute points to that of a pea. In the ventricles of 
the brain the cysticerci may be as large as a small cherry. Occasionally 
compound or racemose cysticerci are met with. 

In some cases the adult worm and the larval form have been found in 
the same individual (man). This is explained by the assumption that 
the eggs have reached the stomach, where the larvae have been set at 
liberty to penetrate the wall of the stomach and thus reach the tissues 
of the body. 

Among the seats of special interest are the brain, the muscles, espe- 
cially the peripheral muscles, tongue and heart muscle, and the sub- 
cutaneous tissues. 

The Adult Worm in Man. — When measled meat (hog, occasionally 
that of deer, sheep, and other animals) is eaten in insufficiently cooked 
form by man the capsules of the cysticerci are dissolved, the scolex 
attaches itself to the mucous membrane of the small intestine, and the 
worm is developed. Usually there is but one worm; occasionally 
several occur in the same case. The worm may remain in the intestine 
for years, despite repeated efforts to dislodge it. In other cases it is 
spontaneously discharged. Reverse peristalsis may cause portions 
to be carried to the stomach, whence they may be discharged by vomiting. 

Geographical Distribution. — -The Tcenia solium is an exceedingly 
rare parasite in America. It seems to be more common in certain parts 
of Europe. 

TiENIA S A GIN ATA 

This form, sometimes called the beef tapeworm, is the common 
tapeworm of man. It is larger than the preceding form, being from 

4 to 8 meters in length, though it may reach 
a length of 35 meters. The head is large 
(2 mm. broad), cuboidal, and provided with 
four suckers. There is an abortive rostellum, 
but no hooklets (Fig. 166). The neck is 
rather long and slender and the segments 
rapidly become broader than long, but in the 
posterior half of the worm, where the sexually 
mature proglottides are found, the segments 
are longer than broad. The uterus is formed 
like that of the Tcenia solium, but the 
lateral branches are more numerous (twenty 
to thirty, and often dichotomously branched; 
see Fig. 163, 1). The eggs are rather more 
oval and larger than those of Tcenia solium, 
but otherwise closely resemble the latter. 

The larval form, or cysticercus, occurs in the ox and sometimes 




ANIMAL PAKASITES AND DISEASES CAUSED BY THEM 



405 



Fig. 167. — Cysticercus 
of Taenia saginata; nat- 
ural size (Leuckart). 



in the giraffe. The measles are found in the muscles, liver, lungs, and 
occasionally in other organs (Fig. 167). 

The adult form occurs only in man, and occupies the small intes- 
tine. The presence of the worm does not seem to occasion any definite 
disease of the intestines, except in rare cases, when 
a number are found present in a coiled mass, or ! r . # 

when one worm is similarly coiled. This may j % J | : Y'[;| 
cause intestinal obstruction, and possibly in ex- j \ v | | 
ceptional instances rupture of the bowel. 

The symptoms ascribed to tapeworms are some 
of them doubtless reflex; but it is noteworthy that 
they are often absent until the patient discovers 
segments in the stools. (Further reference to 
possible pathological results is made in the dis- 
cussion of Dibothriocephalus latus.) It is the 
most frequent tapeworm in America, frequent in 
Southern Europe but is more or less commonly found in all parts of 
the world. 

There is probably no precipitin reaction in the blood, but a comple- 
ment-fixing body has been found. 

HYMENOLEPIS NANA 

This form, sometimes called the dwarf tape- 
worm, in its adult state is 1 to 1.5 cm. in length 
(may reach 2.5 cm.) (Figs. 168 and 169). It has 
a rounded head, with a rostellum that may be 
protruded or retracted and that bears a single 
circle of twenty-two to thirty hooklets. The 
mature segments of the posterior end of the 
worm have a yellow color. The genital pore 
is on the same side in all the segments. The 
eggs are oval in shape, whitish and transparent; 
they are from 0.036 to 0.056 mm. long and 
0.032 to 0.042 mm. broad. 

The intermediary host of this form is not 
certainly known, but is supposed to be some 




Fig. 168. — Hymenolepis nana, about 
natural size (Mosler and Peiper). 



Fig. 169. — Hymenolepis nana, much 
enlarged (Mosler and Peiper). 



form of insect or snail. In the rat the larval form occurs in the in- 
testinal walls at the< base of the villi in the form of a cysticercoid, 
which discharges its contained embryo into the intestine, where it 



406 



A TEXT-BOOK OF PATHOLOGY 



matures. The same sequence may occur in man. The adult parasite 
alone occurs in man. The head attaches itself deeply in the mucous 
membrane of the bowel, and may cause considerable local disturbance. 
There are usually several or many worms associated ; sometimes 
there may be several thousands. 

HYMENOLEP1S DIMINUTA 

This form (probably identical with Taenia flavopunctata) is from 
20 to 60 cm. in length; the head is elongated and verges gradually 
into the neck. The suckers are small, but there is neither rostellum nor 
hooklets. The segments are marked by a yellowish spot which repre- 
sents the male genital organs. It seems to be commonest in children. 
The intermediate host is a species of small moth (Asopia farinalis.) It 
has also been found in several other small insects. 

DIPYLIDIUM CANINUM 

This form is identical with the worm formerly known as Tcenia 
elliptica, and is a common parasite of dogs and cats. The length is from 
15 to 30 cm. ; the head is provided with a rostellum 
bearing sixty hooklets ranged in four rows; the 
rostellum may be protruded or retracted. At the 
junction of the segments there is a considerable 
contraction of the diameter of the worm, giving 
the body a markedly linked character (Fig. 170). 
The mature segments have a reddish-brown color 
from the presence of the eggs. Each proglottis 
has a double sexual apparatus, with a genital 
pore at each side. The intermediary host is 
probably the louse of the dog and occasionally the 
flea. The adult worm usually occurs in numbers 
in the intestinal tract, and in some cases seems 
to produce inflammatory disturbances. 

DAVAINEA MADAGASCARIENSIS 
This form is from 25 to 30 cm. in length; the 
head is marked by four large suckers and a 
Fig. 170.— Dipyiidium rostellum bearing about ninety hooklets. 

caninum (Mosler and 

Peiper). TAENIA ECHINOCOCCUS 

The Tcenia echinococcus or Echinococcus granu- 
losus in its adult form occurs in the upper part of the intestine of the dog, 
less commonly of the wolf and jackal, the larval condition occurring in man 
and in some of the lower animals. The mature worm is about 2.5 to 5 mm. 
in length, and consists of four segments (Fig. 171). The head, which 
constitutes the first, is provided with four suckers and a rostellum bearing 
two to four dozen hooklets in a double row. The second segment is 
about the breadth of the head, but somewhat shorter. The third is 
considerably larger and the fourth is the largest of all, constituting about 
one-half or two-thirds of the entire worm. The uterus consists of a 
median portion with a few lateral branches. The eggs are oval, from 
0.030 to 0.036 mm. in diameter, and the shell is rather thinner than in 
the eggs of other tapeworms. 




ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



407 



These eggs, deposited in water, or on vegetables, or conveyed by 
tactile communication from the body of the dog, are received into the 
mouth of man, and several of the lower animals and a few birds. From 
the stomach or intestine the embryo, liberated by solution of the egg 
capsule, bores its way into the vascular system, by which it may be 
conveyed to any part of the body of its host. 



Echinococcus Cysts. — When the eggs reach the stomach or, more 
probably, the intestine of man the embryo is freed and penetrates the 
mucous membrane. From each egg a single scolex or several scolices 
may arise (Fig. 173). The scolex is carried by the blood or lymphatic 
stream to the liver or other organs, where it develops an echinococcus cyst 
(Fig. 174), of which there may be several varieties. The wall of the cyst 
is composed of two layers, an outer cuticular and an inner parenchyma- 
tous, granulocellular layer. The whole is surrounded by an adven- 
titious capsule of fibrous tissue derived from the organ of the host. 
Within the cyst is a clear, limpid, sometimes amber-colored fluid, having 
a specific gravity of from 1009 to 1015, of neutral or alkaline reaction, 
and containing no albumin or only traces, but a considerable quantity of 
chlorid of sodium, cholesterol, and lipase have been found. A carbo- 
hydrate is sometimes found in the fluid. Hooklets are usually present 
and are of considerable diagnostic value. Such a cyst may increase in 
size, but with no alteration in its general structure, thus forming an 
acephalocyst (Lsennec). This form is found in some of the lower animals 
and in cattle, where it may attain the size of an apple or an orange. 

In other cases large numbers of small hollow " brood capsules" 
are formed within the internal space, in which the order of layers is 
just the reverse to what it is in the parent cyst, that is, they are lined 




Fig. 171. — Tsenia echinococcus, 
enlarged (Moslerand Peiper). 



Fig. 172. — Hooklets of echinococcus. a, of Echino- 
coccus veterinorum; b, of Taenia echinococcus, three weeks 
after infection; c, of the adult Taenia echinococcus; d, the 
three forms of hooklets outlined one within the other. 
600/1 (After Leuckart) . 



408 A TEXT-BOOK OF PATHOLOGY 

inside by a thin cuticle and have the parenchymatous f layer on their 
external surface. From the " brood capsules" the scolices or echino- 




Fig. 173. — Finer structure of wall of echinococcus cyst, showing scolices in delicate cysts 
(from a specimen in the collection of Dr. Allen J. Smith). 

coccus heads develop as external protrusions, at the distal end of which 
the suckers and hooklets of the scolex are formed (Fig. 175). Some 
claim that the scolices may develop directly from the cyst wall without 




Fig. 174. — Echinococcus cyst of the liver (from a specimen in the Museum of the Philla- 

delphia Hospital). 



the medium of the brood capsules. To this form is given the term 
Echinococcus veterinorum or E. scolicipariens. It occurs chiefly in 
domesticated animals. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



409 



In man and only rarely in cattle the mother-cyst may develop 
" daughter-cysts/' which, though smaller than the parent, resemble it in 
the structure of their walls, which are covered externally by a stratified 
cuticle and internally by the parenchymatous layer. They arise from 
small detached portions of the parenchymatous layer in the strata 
of the cuticle of the mother-cyst; they may bulge inwardly or outwardly 
and may separate themselves entirely from the mother-cyst. The 
" daughter-cysts" may remain sterile or may produce brood capsules 
and scolices or other cysts (" granddaughter-cysts")- To this cyst the 
term " hydatid," or Echinococcus hominis or E. altricipariens is applied. 




Fig. 175. — Formation of "brood Fig. 176. — Echinococcus multilocularis 

capsules" upon the parenchymatous (Luschka). 
layer (Leuckart). 

There is another form of echinococcus occurring in man as well as 
in animals and termed Echinococcus multilocularis (Fig. 176). It varies 
from the size of a fist to a child 's head, presents a collection o£. cysts 
from 0.1 to 5 mm. in diameter, and is embedded in a connective-tissue 
stroma. Each cyst is covered with stratified cuticle, and according 
to the size contains either solid cellular contents or a cavity lined with 
a parenchymatous layer. The fluid in this cavity may be transparent 
or opaque, due to the presence of fat globules, bile-pigment if the cyst 
be in the liver, hematoidin, and fat crystals. The cysts are usually 
sterile, though scolices may be" present in some. In man the center of the 
mass disintegrates, leaving a large cavity filled with a brown or greenish 
fluid containing shreds of the wall, calcareous bodies, small cysts, scolices 
and hooklets, fat, hematoidin, margarin, cholesterin, and concretions 
of lime. Nothing positive is known as to the development of this 
form, that is, whether it springs from a single oncosphere or from a 
number of oncospheres", or whether its conformation is brought about 
by peculiarities in its surroundings. 

Echinococcus cysts may continue to grow until they have reached 
huge dimensions without undergoing any secondary changes. In 
other cases the parasite may die and the growth may cease, or active 
proliferation of the tissues around the cyst may lead to early destruction. 
In still other cases suppurative change occurs in the cyst or its wall. 
In all cases when the cyst reaches a certain size the tissues around it 
produce a connective-tissue capsule of greater or less thickness. When 
the parasite dies, inspissation of the liquid occurs, and it may eventually 
disappear or be converted into a thick whitish material; the cyst walls 
and the connective-tissue capsule at the same time shrivel and present 



410 



A TEXT-BOOK OF PATHOLOGY 



peculiar concentric lamellations that are very characteristic. Eventu- 
ally calcification of the wall of the cyst and, to a certain extent, of its 
contents takes place. 

The blood of patients suffering from hydatid disease will fix the 
complement away from the hemolytic series if the contents of a cyst be 
used as antigen. This complement-fixation may be used diagnostic ally. 
The contents of the cyst seem to be toxic, for if they escape in the body 
a severe intoxication results, taking the form of local irritation, inflam- 
mation, fever, and urticaria. 

Seats. — Echinococcus cysts are most frequent in the liver. They 
also occur in the lungs, kidneys, spleen, and omentum, and less frequently 
in the brain or other parts of the nervous system. The pathological 
effects are usually produced by direct mechanical pressure, but may be 
due to the toxin as noted above. 

The geographical distribution is extensive, but the disease is com- 
mon only in restricted localities, especially in northern countries (north 
of Europe, Iceland). 

DIBOTHRIOCEPHALUS LATUS 

The Dibothriocephalus latus is the largest tapeworm of man, reaching 
the length of from 2 to 9 meters or more. The head is flattened and club 
shaped and presents two groove-like suckers at. its 
sides (Fig. 177). The neck is thin and gradually 
increases in diameter. The ripe segments are quad- 
rate, and are distinguished by a rosette-like forma- 
tion of the uterus, which is plainly visible in the 
center of each proglottis (see Fig. 163, 2). The 
genital pore is upon the flat surface of the segment 
and always upon the same side of the worm. The 
eggs are oval in shape and enclosed in a shell pre- 
senting a hinged lid at one pole. The intermediary 
and neck of Diboth- nos ^ * s some form of fish, most frequently the pike, 
riocephalus latus The eggs first undergo a certain amount of develop- 
(Leuckart). ment in water, the embryo becoming free and floating 

about, or being propelled by a ciliated outer covering, 
and then entering the digestive tiact of fish. Transmission of the 
parasite to its human host is believed to be confined to the eating of the 
flesh of infected fish imperfectly salted or cooked. 

The toxic effect of this worm is believed to be due to a hemolytic 
lipoid which is excreted by the worm or liberated by its enzymes when 
acting upon detached proglottides. Extracts of the worm have a marked 
digestive power on protein. 

The geographical distribution is comparatively restricted. It is 
frequent in certain northern countries, as in Sweden and in parts of 
central Europe, especially in Switzerland. It is only occasionally met 
with in America in immigrants. 

DIBOTHRIOCEPHALUS CORDATUS 

This variety is much smaller than the last, the maximum being 
from 1 to 1.25 ii. The head is short, broad, and heart-shaped, and the 




ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



411 



suckers are placed upon the flat surface. The uterine structure differs 
from that of Dibothriocephalus lotus in being narrower and more elon- 
gated, and also in having lateral branches. The body of the worm con- 
tains granular calcareous matter. This parasite is found commonly 
in the seal, the walrus, and the dog in Greenland and Iceland, occa- 
sionally in man also. No doubt its larva lives in fishes. 

DIPLOGONOPORUS GRANDIS 

This parasite measures up to 10 meters in length. The scolex is 
unknown. On the ventral surface are two grooves in which lie the 
genital pores. The ova are brownish, oval, 
measuring 0.063 mm. in length and 0.048 mm. 
in width. It has been observed in Japan. 

Nematodes, or Round-worms 

The round-worms discussed in the following- 
pages are given as the principal representatives 
of this class and as examples of the pathogenic 
capabilities of such organisms. It would be 
impracticable to discuss in a book of this size 
all the forms known to infest man, some sixty 
odd in all, for details of which the student is 
referred to systems on the subject. 

ASCARIS LUMBRICOIDES 

The Ascaris lumbricoides, or ordinary round- 
worm, is one of the most frequent intestinal 
parasites. The male may reach a length of 25 
cm. and a thickness of 2 to 4 mm.; the female 
is longer, up to 40 cm., and thicker, up to 5 or 
6 mm. The body of the worm is brownish or 
sometimes pinkish in color, and presents parallel 
ridges or rings somewhat like those of the earth- 
worm. The head is provided with three rounded 
prominences or lips, between which the mouth 
is placed (Fig. 178). The male shows two 
chitinous spicules at the cloaca. The eggs of 
the worm are produced in great numbers; they 
are elliptical, measuring 0.05 to 0.07 mm. in 
length, and 0.04 to 0.05 in breadth and are 
covered with a tough shell, surrounding which 
is a clear material in an irregular mass. The 
contents of the eggs consist of a granular ma- 
terial, sometimes showing the linear outlines of 
an embryo. 

The ascaris develops in man from swallowing the eggs in infested 
drinking-water or food; personal contact may play a role, it is thought 
by some. The parasites may be present singly or in numbers. Some 
recent studies upon the development of this parasite have led observers 
to conclude that its whole history may occur within man. It is thought 
that the eggs when swallowed hatch in the intestine and shortly migrate 




Fig. 178. — Ascaris lum- 
bricoides: A, female; B, 
male; C, egg, magnified 300 
diameters; b, head, magni- 
fied (after Perls). 



412 



A TEXT-BOOK OF PATHOLOGY 



to other organs, notably the lungs, whence they return to the gut tract 
by coughing and swallowing since they irritate the pulmonary tissue 
enough to set up a bronchitis or pneumonia. After reaching their 
usual habitat they grow to mature size. The fully developed worm may 
migrate from the intestinal tract to the gall-ducts, the stomach, the 
esophagus, and even the larynx or nasal cavities. 

Pathological Physiology. — Ascarides may give rise to violent 
symptoms by obstruction of various passage-ways, and when in numbers 
or united in masses even intestinal obstruction may be caused. It 
is probable that ascarides produce irritating secretions, as it has been 
observed that considerable dermatitis sometimes arises in persons 
handling them. The toxic action has been ascribed to fatty acids and 
irritating volatile aldehyds which have been found in them. Occasionally 
abscess cavities containing lumbricoids are found in connection with 
ulcerations and perforation of the intestines. The abscesses are in part 
due to bacteria gaining entrance with the worms, partly by their se- 
cretions or excretions and partly by their mechanical action. 

OXYURIS VERMICULARIS 

The oxyuris, seat-worm, or pin-worm, is one of the commonest para- 
sites of man. The male is 2.5 to 5 mm. in length; the female, 10 to 12 
mm. (Fig. 179). The posterior end of the male is 
blunt and curved upon itself; in the female it is 
elongated. The eggs of the oxyuris, which are 
produced in great numbers, are oval or elliptical 
and about 0.05 mm. long. The embryo is visible 
within as a lobulated body. The parasite is de- 
veloped directly from the eggs. When these are 
verSculari S :'^?emaS swallowed the outer coating is dissolved in the 
b, male (Mosler and stomach and the embryos escape, to reach their 
Peiper). full development in the small intestine. The im- 

pregnation occurs in the small intestine within a 
short time after the swallowing of the eggs. After impregnation and 
ripening the female parasites move toward the rectum and may be 
discharged, or may leave by their own movements. 

It does not attach itself tightly to the mucosa but seems to injure 
this membrane, possibly by biting, for small hemorrhages are produced. 
Migration out of the anus, about which severe pruritus and eczema may 
arise, is common and the worm may enter the vagina there causing 
inflammation. Autoinfection is believed to arise by scratching the 
irritated perineum and transferring the worms or eggs to the mouth. 
The appendix has been entered also by the parasite, producing true 
inflammation some observers claim. 

TRICH1NELLA SPIRALIS 

This organism occurs . in its larval form in the muscles or organs of 
man and in the lower animals; in the adult form it is found in the intes- 
tines of man or animals. 

The adult male is about 1.5 mm. in length and 0.04 mm. in thick- 
ness. At the posterior end there is a retractile cloaca flanked by two 




ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



413 




projections. The female is 2 to 4 mm. in length and 0.06 mm. in thick- 
ness. The eggs are provided with a very thin shell, and the embryos 
escape from this within the uterus. They are produced in immense 
numbers. The young embryos found in the intestinal tract are from 
0.1 to 0.16 mm. in length, the anterior end being thicker than the 
posterior. 

In part they escape with the feces and die; the greater part pene- 
trate the intestinal wall and are carried to various parts of the system, 
embedding themselves especially in the muscles, where they undergo 
further changes. Here the organism coils itself and becomes surrounded 
with a capsule, which is at first transparent, 

but may subsequently undergo calcareous ijjj 
change and become opaque (Fig. 180). 

Trichinellae are acquired by man by eating 
improperly cooked ham. The capsules are 
digested and the larval trichinellaB set free. 
In the small intestine they reach their ma- 
turity in about three days ; here impregnation 
takes place, after which the males die, while 
the females either bore more or less deeply FlG iso.— Trichineiia cap- 

into the villi or, by way of the glands of sule with its connective-tissue 

Lieberkuhn, penetrate the mucous membrane, 00 YV? n f- a ' f ar1 ^ sta s e - b > 

i wi i i i , -i calcified (Leuckart). 

and so reach the lymphatic spaces, where they 

deposit their young. These are disseminated throughout the body by 
their own migrations or by means of the lymph- and blood-streams. 

The favorite seat is the striated muscle tissue, and they lie within 
the muscle bundles themselves or, less frequently, between them. They 
reach their destination in ten days after the primary invasion, but sub- 
sequent crops are deposited as the young continue to mature in the in- 
testines. In two or three weeks they begin to become encysted in the 
muscles, where they remain alive, capable of development for many years. 

When the embryos are liberated in the stomach and intestines they 
occasion violent gastro-intestinal irritation, with vomiting, diarrhea, and 
Dften more or less pronounced collapse. In their later migration the 
worms set up intense muscular pains of rheumatoid character, with 
edematous swelling and fever. The disseminated disease is called 
"trichiniasis." The pathology of this condition includes, besides myo- 
sitis and gastro-enteritis, fatty liver, nephritis, and infarcts. There is 
undoubtedly an irritative toxin produced, but whether this is wholly 
within the worm or in part made from the degeneration of muscle tissue 
is not certain. There is usually a marked eosinophile increase, the cells 
arising in the bone-marrow from toxin action. The worm uses the 
glycogen stored in the muscles during its growth. No passive immunity 
can be produced with the blood of injected animals. 

Trichiniasis is common in all parts of the world, but has been largely 
reduced by greater care in the cooking of pork. 

ANKYLOSTOMA DUODENALE OR UNCINARIA 
DUODENALIS 

The Ankylostoma duodenale is a cylindrical worm, the female being 
from 12 to 18 mm. in length; the male, from 8 to 10 mm. The head is 



414 



A TEXT-BOOK OF PATHOLOGY 



rounded, bent back like a hook, and is armed with six sharp, hook-like 
teeth, two pairs ventrally, one pair dorsally. The female is usually of 
a brownish or reddish color, due to the absorption of coloring-matter 
from the blood. The elliptical eggs are easily distinguished, from 0.056 
to 0.063 mm. in length and 0.036 to 0.04 mm. in thickness. The shell 
is separated from the contents, and the latter have a granular appear- 
ance, are brownish, and in a state of segmentation. The eggs may 
appear in the stools in great numbers. If now they meet with the proper 
conditions, chief of which are a warm climate and damp earth, they 
hatch out and the active embryo is set free. It rapidly acquires organs 
of digestion and, after casting its skin several times and undergoing 
other evolutionary changes, is ready to re-enter a human host. Loos 
has proved quite conclusively that, while the organism may rarely enter 
the human alimentary canal by the mouth, the probable method of 
entrance is far more complicated. 




Fig. 181. — Ankylostoma duodenale: a, Male, natural size;"*?), female, natural size; c. male, 
magnified ; d, female, magnified ; e, head, greatly magnified ; /, /, /, eggs (von Jaksch) . 

After completing its exogenous phase of development, a suitable 
opportunity offering, the little worm penetrates the skin, generally of 
the feet and legs, of the coolies or others working in or passing through 
the contaminated earth in which the ankylostome ova had been pre- 
viously deposited. The embryo enters the skin through some follicle, 
thence passes into a blood-vessel, and so is carried finally to the lungs. 
Here it leaves the blood-vessels and, undergoing further changes to en- 
able it to resist the gastric juice, enters an air vesicle, passes to a bronchus, 
and so, by way of the trachea, esophagus, and stomach, finally arrives 
at the small intestine. Sexual characters are now assumed and repro- 
duction commences, the ova falling into the contents of the gut and so 
passed out in the stools. 

The adult worm may be present in small or large numbers, and is 
usually rather firmly attached to the mucous membrane. Changes in 
the latter, however, are not pronounced. 

The method of entrance of the ankylostome to its human host throws 
important light on the condition known as " coolie itch" or "ground 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



415 



itch," which often is a forerunner of the intense anemia and other symp- 
toms of the condition known as ankylostomiasis; " coolie itch" is a sort 
of papulopustular dermatitis generally attacking the feet and legs, and 
at times other surfaces as well, of the coolie laborers on plantations. It 
is probably caused by the passage of the ankylostome embryos through 
the skin. Ankylostomiasis or uncinariasis is characterized by severe 
and intense anemia, abdominal discomfort or pain, general wasting, 
often followed by death. This parasite was also found in many cases 
of Egyptian chlorosis, and was the cause of the intense anemias (perni- 
cious anemia) of the laborers engaged in building the St. Gotthard tunnel. 

NECATOR AMERICANUS OR UNCINARIA AMERICANA 

This parasite is shorter and more slender than the Ankylostoma 
duodenale, the male being 6 to 9 mm. long, and the female 8 to 15 mm. 




Fig. 182. — A, Dorsal view of head end of Ankylostoma duodenale; B, dorsal view of head 
end of Necator americanus. (Drawn to scale to show difference in size. A. J. Smith.) 

long. There are also minute differences in the head and body, though 
the general structure of the two parasites is the same. In place of the 



L 



''"3 





Fig. 183. — A, Caudal bursa and tail of male Ankylostoma duodenale; B, caudal bursa 
and tail of male Necator americanus. (Drawn to scale to show difference in size. A. J. 
Smith.) 

ventral and dorsal oval teeth there are plates or suckers, while deep in 
the mouth opening there is one central tooth and one pair of narrow 



F 



L 



Fig. 184. — Ova of (A) Ankylostoma duodenale; (B) Necator americanus. (Drawn to 
scale to show comparative size. A. J. Smith.) 



straight teeth ventrally and dorsally. The ova are larger than those of 
the Ankylostoma duodenale, being 0.068 mm. in length and 0.038 mm. 
in breadth, otherwise they are similar. This form has been found 



416 



A TEXT-BOOK OF PATHOLOGY 



especially in tropical and subtropical America and in the West Indian 
islands. The conditions produced by the American hookworm are 
similar to those caused by the Old World form, but are probably less 
intense. 

The pathological effect of uncinariasis is toxic. The worms remove 
some blood from the gut wall for their nourishment, but not enough to 
cause the severe anemia of the disease. Small hemorrhages appear in 
the gut. A weak hemolysin is formed, can be extracted from the worm, 
and is probably absorbed by the intestine. There is also an active 
coagulating body in the head of the dog hookworm. There are to be 
found in the body fatty degeneration and hyperplasia of the bone- 
marrow. 

STRONGYLOIDES IN TESTINALIS 

This parasite occurs in two generations or types: the parasitic, 
in which the individual of female habitus represents both sexes and 
reproduces by parthenogenesis; and the free living generation, in which 
the two sexes are represented by different individuals. The parasitic 
generation (Strongyloides intestinalis) lives in the upper intestinal tract, 
boring deeply into the mucous membrane and frequently into the epi- 
thelium of Lieberkuhn's glands both for nourishment and oviposition. 
This form is 2.2 mm. in length and 0.034 mm. in breadth; the mouth is 
surrounded by four lips, the esophagus is almost cylindrical and a quar- 
ter the length of the entire body; the eggs measure 0.050 to 0.058 mm. 
in length and 0.030 to 0.034 mm. in breadth. The eggs develop in the 
intestinal wall, and the rhabditiform larvae, which measure 0.2 mm. in 
length, reach the lumen of the intestine and grow to double or three 
times that size until they are passed out with the feces. With the 
proper temperature (26° to 35° C; 78.8°-95° F.) they develop in about 
thirty hours into the free living generation (Strongyloides stercoralis) . 
This form is sexually differentiated; its body is smooth and cylindrical, 
with pointed tail end. The mouth has four distinct lips; the esophagus 
is short with a double (rhabditic-like) dilatation; there are three small 
curved spicules at the base of the tail. In the males the posterior end is 
rolled up, in the females it is straight and pointed. The males measure 
0.7 mm. in length and 0.035 mm. in breadth. The females measure 1 mm. 
in length and 0.05 mm. in breadth. The ova are thin shelled, yellowish, 
and measure 0.07 mm. in length and 0.045 mm. in breadth. The embryo 
as it emerges from the egg often within the uterus measures 0.22 mm. 
in length and resembles the parent form. After growing to about 0.55 
mm. in length it moults and then takes on the characteristics of the 
parasitic form (strongyloid or filariform larvae). In the European 
strongyloides the free living generation is absent. This may also be 
true in the strongyloides of tropical origin where external conditions are 
unfavorable to the development of the rhabditic form. 

There are, as has been mentioned, two methods of reproduction: 
that by direct transformation of the rhabditiform larvae into filariform 
and then into adults, and the indirect, through the intermediate genera- 
tion. By this arrangement the parasite may reproduce directly if ex- 
ternal conditions are unfavorable, and indirectly when conditions are 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



417 




favorable. The latter method seems to be more common in the tropics 
than in colder countries. The adult form alone is parasitic in the true 
sense, the other form representing only a stage for the perpetuation of 
the species. Unlike the ankylostome, eggs of strongyloides are rarely 
found in the stools excepting after purgation. Infection probably occurs 
through tainted water and food, but some experiments seem to indicate 
that the embryo may penetrate through the skin and thus gain access 
to the body. 

Strongyloides is common in tropical countries, and was first dis- 
covered in cases of Cochin China diarrhea. It is probably capable of 
causing intestinal irritation, and seems rarely present in healthy persons, 
but its pathogenicity is still uncertain. It has recently been discovered 
in the United States. 

TRICHURIS TR1CHIURA 

The anterior portion of this parasite is thin and thread-like, while 
the posterior portion is thicker. The length of the worm is from 4 to 
5 cm., the male being somewhat the smaller. The thicker part of the 
male is curled upon itself and blunt at 
the end, while that of the female is 
straight and more pointed (Fig. 185). 
The eggs are very characteristic, being 
brownish in color, covered with a thick 
capsule, and having at either pole a 
button-like projection (see Fig. 164, d). _ „ m '. 

mi . r. VvrA x r\ a • i ±1 Fig- 185. — Trichuns tnchiura; 

The egg is 0.050 to 0.054 mm. m length natural size . a Female; b, male 
and 0.023 mm. in breadth. (Heller). 

The parasite, commonly known as 
the " whip-worm," occupies the cecum in man, occasionally the 
vermiform appendix, and sometimes the small intestine. It is one of 
the most common intestinal parasites in this country and appears to 
be well distributed over the entire surface of the globe, being particularly 
frequent in children in Syria and Egypt. It does not, as a rule, 
produce serious disturbance, but may cause intestinal or reflex nervous 
symptoms. Recently it has been claimed that the parasite causes 
considerable disturbance by abstracting blood and producing a soluble 
toxin. 

FILARIA MEDINENSIS 

The Filaria or Dracunculus medinensis is a round-worm infesting the 
subcutaneous tissue and the skin. The male has not been recognized 
with certainty, though two observers have found a smaller degenerated 
and partly calcified form in association with the female filaria. The 
female sometimes reaches a length of 50 to 80 cm.; it is yellowish in 
color and exceedingly elastic; the anterior extremity is roundish, the 
posterior terminating in a spine. In general appearance it resembles a 
string of catgut. The body of the worm contains a highly developed 
uterus, which practically fills the cavity of the worm, the intestinal tube 
being crowded to one side. The uterus is found to contain innumerable 
small embryos; these escape when the parasite is ruptured. 

27 



418 



A TEXT-COOK OF PATHOLOGY 



The process or place of impregnation is unknown. When ovulation, 
however, is completed the parasite moves down to the leg or foot of her 
host, whence she will be better able to deposit her young in water, which 
is absolutely necessary for their development. Here she drills a small 
hole in the derma, but does not penetrate the epidermis. Over this a 
small blister or bulla forms which soon ruptures, disclosing the small 
opening in the center of a superficial erosion. When the host now enters 
the water a portion of the uterine tube is forced out through the mouth 
of the worm by the contraction of the musculocutaneous integument 
and ruptures, setting free myriads of the embryo worms. This is re- 
peated at intervals until the entire uterus is expelled and parturition is 
completed. This takes, as a rule, two to three weeks. The worm now 
dies, and is expelled or pulled out bit by bit or entire, with or without 
suppuration. Forcible attempts at removal of the worm from the tissues 
may result in its rupture, thus setting free millions of embryos in the 
tissues, whose presence, associated with suppuration, which usually 
follows, results in a condition of considerable danger to the patient. It 
is, therefore, better to wait until parturition is completed before attempt- 
ing removal of the worm. 

The embryos having been deposited in the water take up their abode 
in the intermediary host, the body cavities of a species of cyclops. They 
enter by penetrating the delicate membrane that unites the plates of the 
ectoskeleton of the crustacean. The life-history from here on is a blank. 
It has been thought that after proper development the parasite is swal- 
lowed in drinking-water while still in the body of the crustacean, or it 
may be after it has escaped from this intermediary. Or it may obtain 
entrance to its human host by boring its way through the skin. 

The organism occurs very abundantly in tropical countries of the Old 
World, notably Arabia, along the coast of the Caspian Sea, in Abyssinia, 
and Guinea. The parasite is sometimes called the Guinea-worm. 

FILARIA BANCROFTI 

Several varieties of filarise have been found in the blood and are 
included under this generic term. The discovery of the organism or, 
rather, of the embryos was made by Wucherer in a case of hematuria. 

The embryos of Filaria bancrofti or F. sanguinis hominis appear in 
the blood, urine, the lymph, and the tissues as thread-like structures, 
varying in size in the different varieties. The ordinary form has a 
thickness of about the diameter of a red corpuscle, and is as much as 
0.13 to 0.3 mm. in length. It consists of a transparent sheath, almost 
completely filled with the embryo, the ends, however, projecting a little 
beyond the organism in a sac-like fashion (Fig. 186). The embryo is 
actively motile, squirming, thrashing, or curling and uncurling itself 
rapidly, and thus producing more or less agitation of the corpuscles or 
solid bodies in its vicinity. 

The number of the embryos found in the blood varies greatly; in 
many cases a search through several cover-glass preparations may be 
necessary to detect a single one. Usually they are more abundant. 
A feature of importance is that they swim in the blood stream at definite 
times of the day according to the species (see below) . 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



419 



The adult worms occupy the lymphatic channels, the male and female 
being found together. The male is colorless and measures about 40 mm. 
in length and 0.1 mm. in thickness. The cephalic extremety is a little 
thickened, the posterior extremity is bent and rounded, but not spiral. 
The female is brownish, 76 to 80 mm. in length and 0.2 to 0.3 mm. in 
thickness. Both extremities are rounded. Almost the entire body 




Fig. 186. — Filaria embryo, alive in the blood (F. P. Henry). 



is occupied by the two uterine tubes, in which may be seen the ova and 
already developed larval filarise. These enter the circulation and are 
discharged in various ways, especially in the urine. The common 
tropical mosquito (Culex fatigans) has been found to act as the inter- 
mediary host in which the embryo reaches its fuller development. The 
embryo filarise are taken into the midgut of the mosquito together with a 
certain amount of blood at a time when the filariae are found in the 
peripheral circulation. Here in the thickened plasma the embryos 
are able by their active movements to break through their sheath. 
Now, by means of a short delicate spine and a circle of hooked lips at 
the head end, the organism bores its way to the thoracic muscles of the 
mosquito. Here in the course of one to three weeks it goes through a 
series of changes and increases considerably in size. It now works its 
way to the head of the mosquito, and finally passes down into the 
labium or sheath of the proboscis, where it awaits the opportunity to 
enter a human host when the mosquito next feeds on man. It then finds 
its way into the lymphatic trunks, where the sexes come together and the 
young are born. 

Filariasis is particularly common in the warmer climates, but is 
occasionally met with in this country, especially in the Southern States. 
One of its most frequent forms is • characterized clinically by hemato- 
chyluria. The embryos in these cases may be found in the blood and also 
in the chylous urine. Pathologically, no gross changes may be found, 
but there may be in other cases evident distention of the lymphatic 
channels and blood-vessels of the pelvis of the kidneys, ureters, or 
bladder; and the embryos may be found in the substance of the kidneys 
or in the walls of the blood-vessels. Another form of filariasis is ele- 
phantiasis. In these cases there is obstruction of the lymphatic vessels 
in consequence of the presence of the parasites, of thrombi, or of inflam- 
matory lesions, and as a result of these conditions dilatation of the 
peripheral lymphatic, vessels occurs. The skin may be ruptured and 



420 



A TEXT-BOOK OF PATHOLOGY 



chylous liquid may exude. The embryos may be found in this on micro- 
scopical examination. 

Varieties. — Manson has described three varieties of embryonal 
filarial — the original form, or Filaria nocturna; a second variety, in 
which the embryos are found at any time, night or day, called Filaria 
perstans, characterized also by its small size (0.2 mm. in length), great 
motility, and absence of a sheath; this he believes is the cause of certain 
skin diseases (craw-craw) of Africa; the adult worm is unknown. The 
third form is the Filaria diurna, which appears in the blood only during 
the day. The last is probably the embryo of Filaria loa, a wandering 
form frequently occurring in the eye, lying under the conjunctiva. It 
is found in Africa and tropical America. Manson believes that the 
mangrove fly is the intermediary host. 

OTHER FORMS OF FILARIA 

The Filaria lentis was found in the lens in a case of cataract; the 
F. labialis was discovered in a pustule on the lip of a student in Naples; 
the F. hominis oris was found by Leidy in the mouth of a child; and 
F. restiformis was found in the urine of a patient by the same observer. 
The F. immitis is the common filaria of the dog, and has been found in 
man. The F. ozzardi was found in the blood of Caribs of British Guiana; 
it is the same as F. demarquayi; is shows no periodicity being, present 
in the blood at all times of day. The F. loa is confined to Western 
Africa. The F. bronchialis was found in the bronchial lymphatic glands 
in a case of phthisis, and has also been found in the trachea and bronchi. 
F. conjunctivas, F. lymphatica, and F. romanorum-orientalis are others 
that have been described. 

ECHINORHYNCHUS GIGAS 

This is a large round-worm, the body being marked by distinct, 
transverse, parallel rings. The male may be from 7 to 10 cm. in length, 
the female from 31 to 50 cm. There is a retractile rostellum, with six 
rows of hooklets at the anterior end, each row composed of eight spicules. 
The parasite occupies the small intestine of the hog, and has been found 
occasionally in man. The intermediate host seems to be the grub of the 
cockchafer and the June-bug. 

Other varieties of echinorhynchus have been described, but are not 
well-determined species. 

EUSTRON GYLUS GIGAS 

The female of this species may reach a length of 1 meter; the male is 
but one-third the size. The anterior end of the worm is retracted and 
the mouth surrounded by six papillae. The posterior end is expanded 
and provided with a spicule projecting from the cloaca. The color of the 
worm is brownish or blood red. The parasite is found in the pelvis of the 
kidneys, ureters, and bladder of dogs, horses, cattle and other animals, 
and rarely in man. Among its results are enlargement of the pelvis of the 
kidney and atrophy of the kidney substance. 



ANIMAL PARASITES AND DISEASES CAUSED BY THEM 



421 



STRONGYLUS APRI 

This parasite was found in the lungs of a child. It resembles the 
strongylus met with in the lungs of sheep and other animals. 

STRONGYLUS SUBTILIS 

This organism has been described by Loos as being found in the 
intestines at autopsies of natives of the Egyptian lowlands. 

Annelides 

Two forms of leeches are of some pathological importance. The 
Hirudo ceylonica is a form occurring with great frequency in Ceylon 
and other islands, and in parts of South America. It is found in vegeta- 
tion, and attaches itself to the skin of the legs and to other parts of man 
by means of a sucker and its short teeth. It may give rise to painful 
ulcerations when removed. The Hirudo vorax is met with in parts of 
Europe and Africa. It gains access to the mucous membranes of the 
mouth, larynx, trachea or nasal chambers, and leads to inflammatory 
troubles. It is not able to effect a lodgment upon the skin. 

Arthropoda 

A number of parasites belonging to the groups Arachnoidea and 
Insecta are met with in man. Most of these, however, are purely 
external parasites, and are fully described in works upon diseases of the 
skin. There are two forms, however, that merit brief description here: 
the Linguatula rhinaria, its larval form of Pentastoma tcenioides; and 
the larvae of various flies, the presence of which in the gastro-intestinal 
tract and other parts of the body is termed myiasis. 

LINGUATULA RHINARIA 

This parasite is occasionally found in the liver, and rarely in the 
spleen, intestinal walls, lungs, and kidneys of man. It is discovered in 
small nodular lesions, which consist of the more or less degenerated 
parasite lying in a cheesy or semicalcified material, surrounded by a 
fibrous or calcareous capsule. The parasite is from 4 to 5 mm. in length 
and 1.5 mm. in breadth; has a rather rounded body, which is encircled 
by parallel rings armed with spicules; and is provided with two pairs of 
stout chitinous hooklets, one pair lying on either side of the mouth. 
The adult form, Linguatula rhinaria, resembles its larva in structure, 
but is considerably larger, the male being from 16 to 18 mm. long, the 
female from 80 to 100 mm. This form lodges in the nasal cavities and 
frontal sinuses of the dog and other animals, and produces eggs contain- 
ing the embryos, which escape with the nasal secretion and eventually 
gain access to the alimentary tract of other animals or of man. 

POROCEPHALUS CONSTRICTUS 

This species has been discovered in man in a few cases, and only 
in its larval form. It differs from Linguatula rhinaria in being larger 
(10 to 14 mm. in length) and having a smooth surface. It has been found 
in the peritoneal cavity, intestines, liver, and lungs. 



422 



A TEXT-BOOK OF PATHOLOGY 



MYIASIS 

A number of flies, of the orders Estridae, Musca, Lucilia, and Sar- 
cophaga, may deposit their eggs in wounds or in cavities of the body to 
which they gain access, such as the nasal or pharyngeal chambers and 
the communicating passages. The eggs so deposited are hatched, and 
the larval insects may be retained and may occasion intense irritation. 
Sometimes the larvae are found in the gastro-intestinal tract, the eggs 
having been swallowed with food. Immense numbers may be discharged 
from the intestines, and in some cases the larvae seem to occasion intes- 
tinal irritation. The term myiasis is given to the invasion of these 
larval insects. 

The foregoing are accidentally parasitic but other ectoparasites with 
definite activity for the human being are to be found among the wingless 
acarians and mites. The former are represented by lice, Pediculus cap- 
itis, corporis and pubis, the latter by the itch mite, Sarcoptes scabiei 
and Dermacentor venustus. The former group bite or suck the skin but 
do not enter; lesions of the skin where they bite are due wholly to 
scratching. The mites penetrate the epithelium while beneath their 
"burrow" a slight infiltration of the corium arises, to which may be added 
any lesions due to scratching. t 



CHAPTER XI 



THE METHODS OF TRANSMISSION OF THE COMMUNI- 
CABLE DISEASES 

The develpment of a communicable or infectious disease requires 
the entrance of a disease-producing agent into the body, which agent 
must exist in nature in such a form that it can be conveyed to or 
into the body. The paths of infection have already been discussed, 
and it remains to be considered here how the viruses are brought to 
these paths. Sanitarians have supplied data which permit the classi- 
fication of the transmission of disease as direct, indirect, and through 
an intermediate host in which the virus must pass through some cycle 
of development. 

The sources from which diseases are disseminated are human beings 
and lower animals'. There are a few conditions, like ergot-poisoning and 
pellagra, exhibiting a clinical and pathological course much like an infec- 
tion, which seem at this time to be traceable to the vegetable kingdom. 

The diseases that pass from human being to human being far out- 
number those contracted from animals, and many are truly specific 
for man; for example, the acute exanthemata are diseases of the human 
race alone, and only very exceptionally can be transmitted experimentally 
to the Tower races. As a natural corollary it follows that man is the 
greatest disseminator of infectious disease among men. Many infec- 
tions more or less specific for the lower animals are transmissible to 
man, but do not, as a rule, assume epidemic forms, while acute infections 
peculiar to man and spread by him tend to appear epidemically or 
endemically. In like manner, animals are the most important means 
of dissemination of infection among animals. 

The transmission of disease from man to man occurs by direct con- 
tact, such as handling or kissing; indirectly, as in the use of infective 
linen, eating utensils or taking infective material into the mouth, or by 
an intermediate host, as the mosquito in malaria. 

From animals men are infected chiefly by handling or by the par- 
taking of infected milk or meat. Biting is of great importance, as 
exemplified by rabies. Man is infected by plants usually by eating, but 
simple handling of some plants, like poison ivy, produces a condition akin 
to infection in susceptible persons. Diseases are propagated among 
animals chiefly by direct contact or by infective food. When one 
animal of a herd or flock becomes infected it is easy for it to infect the 
common food supply, be it pasture, crib, or pan. The importance of 
this lies in the fact that a milk-giving herd may be infected throughout 
by one new member and render the milk unfit for human use. 

423 



424 



A TEXT-BOOK OF PATHOLOGY 



Direct Infection. — Contact Infection. — This group embraces those 
diseases which demand for their dissemination a rather intimate personal 
relation of the sick and well, either by touching or the intervention of 
air or droplets in the expired air. It is doubtful if any infection is trans- 
ferred in this manner only, but certain diseases are so contracted in 
the vast majority of cases. For example, the venereal diseases — lues, 
gonorrhea, and chancroid — are practically always acquired by the intro- 
duction of the germs into skin or mucous membrane abrasions by direct 
inoculations from infected persons. Their causative organisms survive 
exposure to conditions outside the human body for a very short time. 
Drying is fatal to the Spirochceta pallida and the gonococcus in a few 
hours. Chicken-pox is an acute infection that seems at the present day 
only transmissible directly, that is, it is not carried by a third person. 
Rabies is a good example of direct infection, for it is obligatory that the 
fresh virus be introduced beneath the skin. While the exact means of 
transmission of leprosy is not known, it is probable that direct contact 
is necessary for its acquisition. 

Aside from these contact infections, direct transmission is air borne 
by the dissemination of bare germs or those contained in finely divided 
droplets of sputum or saliva, or carried in dust. It is to be emphasized 
that no sharp line can be drawn between direct and indirect transmission, 
because all those diseases which may be carried by f omites and food can 
be acquired by the direct passage of infective matter from the sick to 
the well. Since we have learned that methods of transfer of a virus 
must permit of a retention of its virulence and that this disease producing 
power declines after leaving the body, it follows that objects freshly soiled 
with secretions or excretions are the most dangerous. There are some 
infections, like diphtheria, scarlatina, mumps, small-pox, and measles, 
whose spread is possible merely through the air and yet can be carried 
by f omites and by a third person, particularly if the exposure to the patient 
has been recent. These may be called the air-borne infections when 
emanations from the sick person are carried to the well merely through 
the air. The exact course of travel is not known for those diseases whose 
causative agent has not been isolated, e. g., small-pox. In the bacterial 
diseases, like tuberculosis, diphtheria, pneumonia, plague, influenza, 
micro-organisms are loosened from the patient's person by coughing, 
or the drying of secretions or excretions, and blown about by air cur- 
rents. They may settle upon surfaces, whence they are again carried 
to the well by air or contact. The most important factors in dis- 
semination of bacteria by such means are coughing and sneezing, 
which forcible expiratory actions project infective matters considerable 
distances. It is said that tubercle bacilli may be thrown twenty feet 
in front of a coughing consumptive. Few, if any, micro-organisms are 
to be found in the breath during quiet respiration. The bacteria are 
carried by droplets of sputa: These fall and dry upon surfaces, to be 
pulverized and removed by air or contact. Dust is also a carrier of germs 
and serves as a protection for them, as it keeps away light. The viruses 
of communicable diseases are for the most part quickly destroyed by 
exposure to direct light, but if protected by some envelope, as mucus 
about a tubercle bacillus, their infectivity is indefinite. Disease germs 



METHODS OF TRANSMISSION OF THE COMMUNICABLE DISEASES 425 

are common in dust and dirt that dry upon floors and walls of public 
places. In public places or conveyances, houses, hospitals, schools, 
and workshops this sputum and dust transmission is of great importance. 
Bacteria are not widely disseminated out of doors by air currents, since 
they soon perish by exposure. It is a common belief that odors from 
sewers carry with them dangerous bacteria. While germs may be pro- 
pelled several feet by the bursting of bubbles in sewage, the number of 
pathogens escaping has been found to be practically none so that this 
means of producing illness is negligible. 

Indirect Transmission. — This takes place when the agent passes 
from the sick to the well by some conveyance which permits the virus 
to grow or at least to sustain life. The vehicle may be water, food, soil, 
insects or human beings, or more passive carriers, called fomites, like 
infected bed or body clothing, towels, drinking cups, and eating utensils. 
In these transmissions we assume that the germs are simply carried by 
the vehicle as a passenger and that the vehicle itself exerts no influence 
upon them. By a prolonged existence in the vehicle and, therefore, ab- 
sence from the human body, the pathogenic organisms may become 
reduced in virulence, so that freshly soiled things are the most dangerous 
as was noted before. 

Water transmission, according to present knowledge of disease, is 
confined to typhoid, cholera, and perhaps dysentery, both of the bacil- 
lary and amebic type. No definite limit can be set for the life in water 
for the germs of these diseases, but it may be months. 

Food Transmission.— The most important food-carrier of disease 
is milk. Typhoid fever, diphtheria, septic sore throat, and scarlatina 
are carried by milk when contaminated during collection and dis- 
tribution by persons suffering from these diseases or by carriers. In- 
fected water used to wash cans or to dilute milk may introduce typhoid 
bacilli. Diseases originating in the animals supplying the milk, as tuber- 
culosis, foot-and-mouth disease, and Malta fever, are transmissible to 
man. The transmission of tuberculosis by milk of tuberculous animals 
cannot be doubted. 

Vegetables convey disease only when contaminated by surround- 
ings in cultivation or in the process of preparation for food. Oysters 
and other shell-fish when taken from polluted water may convey typhoid 
fever and cholera. Meat conveys animal parasites and acute bacterial 
and toxin diseases like paracolon and paratyphoid fever, botulism, and 
ptomain-poisoning. Tuberculosis is undoubtedly transmissible by in- 
fected meat. 

Soil Transmission. — There are many organisms in soil, but few of 
the varieties are pathogenic for man. Certain pathogens, like typhoid 
and plague bacilli and cocci, are occasionally to be found, but are of little 
importance in hygiene. In plague centers the soil is said to be fre- 
quently infected with plague bacilli. The organisms most frequently 
found in the soil that produce specific infections in man are those of 
tetanus, anthrax, malignant edema, gas bacillus poisonings and sympto- 
matic anthrax. The life of these germs in soil is favored by their spore 
formation. 



426 



A TEXT-BOOK OF PATHOLOGY 



Insect Transmission. — This may be direct or indirect. The former 
includes those transmissions in which the insect acts as an interme- 
diate host of the virus, permitting some developmental phase in it, 
a subject to be considered later. Indirect or mechanical transmis- 
sion occurs when the insect becomes infested , with human pathogens 
and carries them passively to situations where they can infect human 
beings. Thus, flies may carry typhoid bacilli upon their bodies from 
dejecta to food; fleas transfer plague bacilli from human cases or infected 
rats. There is a class of disease transmitted by biting insects in which 
it seems that the virus does not pass through a cycle of development 
in the body of the insect. The virus remains in an infective condition 
within the intermediate host for various lengths of time and may be 
transmitted to the young. In this class may be included typhus, re- 
lapsing fevers, Rocky Mountain fever, and trypanosomiasis. It may be 
found later that a cycle of development occurs in these insect bearers. 

Animal Transmission. — Animals may act as passive carriers of such 
diseases as diphtheria, scarlet fever, or measles by association with in- 
fected persons. The cat is one of the commonest of such conveyors; it 
is frequently responsible for the spread of the mycosis favus. Animals 
act as active carriers of various worms. Certain diseases, like actino- 
mycosis and rabies may be transmitted to man by animals. 

Human Transmission. — Human beings transfer infection in one of 
three ways: (a) when actively suffering from disease; (b) passively from 
sick to well upon person or clothing, and (c) as "carriers." The opera- 
tion of the first and second methods is obvious; it is to be understood 
that under the second heading the conveying person is not ill with 
the disease he is transmitting. "Carriers" are persons who having 
suffered from a disease have not destroyed or discharged all the virus 
from the body when recover took place. This virus has remained in 
some locality protected from the action of the blood-serum, or by long 
sojourn in the body has become immune or "fixed" or "fast" to the 
bodily defenses. Under certain circumstances it may leave the body 
and infect others. Thus, after typhoid fever, typhoid bacilli may re- 
main in the alimentary tract for years, passing out with feces and con- 
taminating surroundings or the water and food supply. This also 
occurs after cholera and diphtheria; in the latter case Klebs-Loffler 
bacilli remain in the throat a long time. These persons might be called 
"chronic carriers," while the persons who merely passively transfer 
infection might be termed "accidental carriers." During an 
infectious disease the patient is, of course, a carrier, and might be spoken 
of as an "infected carrier." The term "carrier" has, however, lately 
acquired a wider meaning covering persons who have in their body 
the virus of a disease, and thus the power of infecting others, although 
the carrier has never suffered with the infection in question. It has 
been found that a considerable percentage of people may have in their 
nose and throat the coccus of meningitis, the bacillus of diphtheria, or 
in the intestinal tract the organism of the typhoid fevers without being 
aware of this state and without knowledge of how it was acquired. Such 
individuals, "hidden carriers," are obviously of great danger to the 
public and are doubtless responsible for the continued presence of com- 



METHODS OF TRANSMISSION OF THE COMMUNICABLE DISEASES 427 

municable disease in crowded communities. Instances of this sort are, 
besides those already mentioned, dysentery and poliomyelitis; perhaps 
later we shall learn that the same thing holds good for measles, mumps, 
scarlatina and the like. 

Transmission by inanimate objects or fomites is purely mechanical. 
It is of importance in all infectious diseases except those only transferred 
by insects. 

Insect Transmission with a Cycle of Development in the Interme- 
diate Host. — This is a group differing from the indirectly insect-borne 
diseases, in that a period of time must elapse between the reception of 
the virus in the body of an insect until it becomes infective for man. 
The diseases whose transmission by this means seems now proved beyond 
doubt are malaria, yellow fever, filariasis, and dengue. Mosquitoes are 
the "intermediate host" and man is called the "definitive host." Ticks, 
flies, and other insects also transmit disease and may permit some 
form of development, but this is not yet proved. 

Despite the fact that in all insect-borne diseases the viruses do not 
have the same biological history, there are many analogies among them. 
The insects concerned are biting or suctorial, and include mosquitoes 
carrying the viruses above mentioned; ticks, transmitting relapsing 
fever, Rocky Mountain fever, and tick fever; flies, transmitting trypano- 
somiasis; and lice, believed to convey typhus. 

The viruses of dengue, and the tick fevers have not yet been isolated, 
but epidemiologically their connection with insects is well established. 
The insect transmitting African relapsing fever is known, but the other 
forms are still in doubt. (See page 357.) 

These insect-borne diseases are transmitted always by the same 
species of intermediate host, and the virus seems specific for species in 
the definitive host. One insect seems to carry only one form of virus. 
The contagium does not harm the carrier so far as known. The diseases 
appear only where their respective insects live, and when they spread 
it is the definitive host which carries them, since the insects do not 
travel far. These infections are not directly communicable. There is 
a definite and quite constant incubation period peculiar to each disease 
for both the intermediate and definitive host. Ticks are the only 
ones that transfer the virus to their young. 



PART II 



SPECIAL PATHOLOGY 



CHAPTER I 
DISEASES OF THE BLOOD 
ANATOMY 

The blood -is a liquid tissue composed of corpuscles or cells and a 
fluid intercellular substance. The cells are of three kinds: the red 
corpuscles, or erythrocytes; the white corpuscles, or leukocytes; and the 
blood-plaques, or platelets. The fluid element of the blood, the liquor 
sanguinis, or plasma, is an albuminous and saline liquid of a slightly 
varying composition. The blood as a whole is red in color, rather viscid, 
and alkaline to ordinary indicators, though actually neutral in reac- 
tion. The total quantity is about one-thirteenth of the body-weight. 

The erythrocytes, or red corpuscles, are biconcave disks averag- 
ing 7 m in diameter and having a yellowish or amber color. They are 
quite uniform in size and regularly rounded. Histologically they are 
composed essentially of an albuminous substance containing hemoglobin 
embedded in a delicate stroma. The hemoglobin is the important ele- 
ment, and constitutes about 95 per cent, by weight of the corpuscles. 
In early fetal life most of the red corpuscles are nucleated, but the nu- 
cleated forms later decrease in number and are comparatively scanty at 
the time of birth. Within the first few months of postfetal life all of 
them disappear, and in subsequent years nucleated corpuscles are 
present only in cases of disease. According to some recent investiga- 
tions it would appear that the red cells of adult human blood always 
contain nuclei demonstrable only by certain staining methods. The sup- 
posed nuclei shown in some of these methods are certainly artefacts. 
As to others, further investigation is needed. 

There are about 5,000,000 red corpuscles in the cubic millimeter of 
the blood of normal individuals. The figures vary slightly at different 
times in the same individual, and many influences contribute to the 
production of more lasting changes in number (see pp. 436, 446). The 
volume of the red corpuscles in»a given bulk of blood is dependent upon 
their number and their size. Observers have reached varying results in 
studying the volume, but it may be placed at between 40 and 50 per 
cent, of the total bulk of the blood. 

429 



430 



A TEXT-BOOK OF PATHOLOGY 





DISEASES OF THE BLOOD 



431 



Skeined Cells. — The method of vital staining that has been recently 
introduced discloses certain varieties of erythrocytes that have excited 
discussion. A drop of blood is mixed with oxalated sodium chlorid solu- 
tion, to which brilliant cresyl-blue has been added. The sedimented 
red corpuscles are then placed under a cover-glass and examined. 
A certain proportion of the erythrocytes are found to present a skeined 
or reticulated appearance, which is due to the presence of granules con- 
nected by fine threads or a variously arranged network of threads or 
granules stained by the coloring-matter used. These cells have been 
regarded by some as degenerative forms, but are more probably young 
cells. In various anemias in which active hemogenesis is going on, the 
skein cells are more abundant than in normal blood. 

The leukocytes, or white corpuscles, are rounded or spherical 
bodies presenting a more or less granular appearance in the fresh state. 
They vary in size from the diameter of the red corpuscles to several 
times the size of the latter. There are several more or less distinct 
varieties of leukocytes, but as transitional forms occur classification is 




Fig. 189. — Unstained leukocytes. 



difficult (Fig. 189). The terminology introduced by Ehrlich is still in 
quite general use, though recent authorities have disputed many of his 
views regarding the relationship and source of different forms. Refer- 
ence will be made to these points in the discussion of the origin of leu- 
kocytes. 

Ehrlich distinguished the following forms in normal blood: (1) 
Lymphocytes; (2) large mononuclear; (3) transitional; (4) polymorpho- 
nuclear; (5) eosinophils, and (6) basophiles. The last occur in only 
very small numbers in normal blood, and when in larger proportions 
signify pathological conditions. 

1. Lymphocytes. — These are, on the average, about the size of red 
corpuscles, some a little larger, others smaller; they are spherical in 
shape and contain a relatively larger round nucleus surrounded by a 
narrow band of protoplasm often so slight that it is scarcely visible. 
The nucleus is rich in chromatin, staining deeply with basic stains, and 
containing one or two nucleoli. Occasionally it is oval or slightly in- 
dented on one side. Frequently and often quite strikingly the nucleus 
is surrounded by a clear zone occasioned by lesser density of the intra- 
protoplasmic network in that situation. The protoplasm is slightly 
basophile and with Giemsa or Leishman's stain may present somewhat 
sparse, fine or coarse granules (azur granulation). The lymphocytes 
constitute 20 to 25 per cent, of the normal leukocytes. 

2. Large Mononuclear Leukocytes. — These are called by some 
" large lymphocytes," and, undoubtedly, with certain stains a distinction 



432 



A TEXT-BOOK OF PATHOLOGY 



between the larger forms of lymphocytes and certain large mononuclear 
forms is impossible. Other names such as endotheliocytes and splenocytes 
have been suggested by authors who claimed a definite origin for these 
cells. The size varies from 15 to 25 ju; the cell is ovoid and contains a 
rather large (7 to 10 /a) round nucleus which is relatively poor in chromatin, 
so that in the stained blood it is much paler than that of the lymphocyte. 
There is no nucleolus. The protoplasm is feebly basophile, with only 
occasional granulation (azur granules). The clear non-granular charac- 
ter of the protoplasm has suggested the term " hyaline cell. " With deep 
Giemsa staining the protoplasm is said to contain an abundant fine 
granulation regarded by some as azur granules and by others as a special 
sort. 

3. Transitional Leukocytes. — These are similar to the last, but 
differ in that the nucleus is indented or somewhat irregular in outline. 
It is very often impossible to determine satisfactorily whether a certain 
cell is a large mononuclear or a transitional form, and the two may be 
considered as practically the same. The protoplasm may be free of 
granules, or may present fine neutrophilic granulation. The large 
mononuclear and transitional forms together make up 4 to 8 per cent, 
of the normal leukocytes. 

4. Polymorphonuclear Leukocytes; Polynuclear Leukocytes; Neu- 
trophiles. — These are the most numerous forms. They are somewhat 
smaller than the large mononuclear elements, being from 10 to 12 fi 
in diameter, and are distinguished by a polymorphous nucleus which 
is richer in chromatin than that of the large mononuclear form, though 
less rich than that of the lymphocyte. The nuclei are elongated and 
variously curved or distorted, so as to resemble the letters S, U, V, Z, 
etc, and in some cases they are wreath shaped. Frequently, parts of 
the nucleus are so thin that they are scarcely visible, or actually be- 
come broken, and the term " polynuclear" was, therefore, applied. 
This name is, however, less accurate than the term "polymorphonu- 
clear." The amount of chromatin in the nucleus varies greatly, and 
the size of the nucleus is correspondingly variable. The protoplasm 
usually contains fine granules, which are closely set and almost com- 
pletely fill the cell. These granules have a strong affinity for neutral 
mixtures of anilin or other stains, especially for the triacid stain, and 
have, therefore, been called the neutrophilic granules (see p. 434). 
The polymorphonuclear neutrophiles constitute 60 to 70 per cent, of 
the normal leukocytes. 

5. Eosinophiles.— -These are slightly larger than the polymorpho- 
nuclear neutrophiles, their nuclei are polymorphous, though not so 
much divided and not so basic in staining affinity as the nuclei of the 
neutrophile. The protoplasm contains large granules which stain in- 
tensely with acid stains. In pathological conditions certain other cells 
containing eosinophile granules are met with (see Myelocytes). They 
constitute 1 to 4 per cent, of the leukocytes of the normal blood. 

6. Basophiles. — These are polymorphonuclear cells the nucleus of 
which stains poorly with basic stains. The protoplasm contains irregu- 
lar sized granules of intense basic affinity. Not over 0.5 per cent, of the 
leukocytes of the normal blood are of this type. 



DISEASES OF THE BLOOD 



433 



Pathologically, certain other forms of cells of the leukocytes series 
occur in the blood. • Among these are: (a) Myelocytes, (b) plasma cells, 
and (c) leukoblasts. Occasionally myeloplaxes, or marrow giant cells, 
are present. 

(a) Myelocytes. — -These are large cells identical with the large 
granular cells of the bone-marrow. They are often three or four times 
the size of the red corpuscles, and are distinguished by a large, pale, 
oval nucleus generally placed close to one side of the cell. The proto- 
plasm is sometimes entirely free of granulations, but usually contains 
fine neutrophile granules. Eosinophile and basophile myelocytes are 
less frequent, but are sometimes seen in fairly considerable numbers in 
leukemia. The nucleus is frequently somewhat irregularly outlined, 
and not rarely suffers degenerative change. Smaller cells, resembling 
the typical myelocyte in the character of the nucleus and protoplasm, 
are sometimes observed, and are difficult to classify. Myelocytes occur 
in exceedingly small numbers, if at all, in normal blood. They are abun- 
dant in certain forms of leukemia, and also occur in pernicious anemia 
and various infectious and systemic diseases. 

(b) Plasma Cells, Stimulation Cells, Irritation Cells (Turck). — 
These are oval cells, varying in size from 5 to 15 /* in diameter; and 
contain an eccentrically placed round or oval nucleus. Both nucleus 
and cytoplasm are decidedly basophile, especially the latter. There 
are no true granules, but the deeply stained cytoplasm often presents an 
indefinite granular appearance. Great variation in the character and 
staining reactions have been noted by different investigators, and an 
accurate definition is, therefore, difficult. 

(c) Leukoblasts. — in various blood diseases, especially in acute leu- 
kemia, there are found certain spherical cells varying in size from 8 to 
20 m in diameter, and containing a large, somewhat eccentric nucleus, 
poor in chromatin, and a non-granular cytoplasm. These cells have 
been regarded by some as lymphocytes and by others as non-granular 
myelocytes, but are now more generally considered as primitive or 
mother-cells of the leukocyte series, and have, therefore, been named 
leukoblasts, primordial cells, myeloblasts, or lymphoblasts. 

(d) Myeloplaxes, or megakaryocytes, are large cells, sometimes sev- 
eral times the size of myelocytes, containing a large, highly polymor- 
phous nucleus, and a moderately granular cytoplasm. These cells are 
occasionally found in the circulating blood in severe anemias. 

The granules of the leukocytes are classified according to their be- 
havior with the anilin stains. Ehrlich distinguished four important 
types of granules. 

(1) a-Granules, Eosinophile Granules, or Oxyphile Granules. — These 
are coarse granules giving the appearance in the unstained blood of 
minute fat-droplets; they are highly refractive, and have been shown 
to be composed of albuminous material. They are distinguished by their 
strong affinity for acid stains, and in particular for eosin. This circum- 
stance has given rise to the names eosinophile and oxyphile. 

The eosinophile granules in the normal blood occur only in poly- 
morphonuclear leukocytes. 



28 



434 



A TEXT-BOOK OF PATHOLOGY 



(2) 7-Granules ; Mast-cell Granules. — -These are intensely basophilic, 
coarse granules, occurring in mononuclear cells. The mast-cell is iden- 
tical with Waldeyer's plasma-cell of the tissues. It is present in small 
proportions in the normal blood. 

(3) 5-granules are fine basophilic granules occurring in the lympho- 
cytes or large mononuclear cells. • 

(4) e-Granules; Neutrophilic Granules. — These are the most abun- 
dant and the most important of all the forms. They occur as fine granu- 
lations, filling up the protoplasm of the polymorphous cells, and they 
are occasionally present in transitional leukocytes. They are distin- 
guished by their affinity for the neutral mixtures of Ehrlich. It must 
be recognized, however, that these granules are, in reality, faintly 
oxyphilic, receiving the acid stains, such as eosin or acid fuchsin, more 
readily than basic stains. 

In recent years by newer methods (Leishman, Giemsa) a special 
form of granule, "azur-granules," has been distinguished and has been 
regarded as highly significant, especially of cells of the lymphocytic 
series. This view, however, is far from being established. Not im- 
probably immature granules of myeloid cells also present this staining 
reaction. 

Altmann and, later, Schridde and others have described certain 
fuchsinophile extranuclear granules which are regarded by some as 
highly characteristic of the lymphocytic series of cells. The significance 
of these granules is very uncertain. 

The nature of the granules of the blood is still obscure. They are 
undoubtedly connected in some way with the specific function of the 
leukocytes, but whether they are specific cellular secretions (Ehrlich) or 
essential anatomical structures (Altmann) is unknown. 

While there are wide variations in the classifications of the types of 
leukocytes and in the views of investigators as to their origin and rela- 
tion to each other, for practical purposes we may consider them in three 
classes : 

(1) Lymphocytes or lymphoid elements, derived from lymphatic 
nodes or lymph-adenoid tissues, 

(2) Polymorphonuclear (granular) cells — neutrophilic, eosinophilic 
or basophilic derived from the bone-marrow, and 

(3) Large mononuclear and transitional — cells of uncertain origin. 
Many attempts have been made to devise staining methods by which 

cells of one series might be certainly distinguished from those of another 
such as those in which azure granules or fuchsinophile bodies are shown. 
Most of these have thus far proved entirely unsatisfactory. The demon- 
stration of oxydases in cells of the myelocytic series (oxydase staining) 
seems at present the most reliable distinguishing feature between these 
cells and lymphocytes. 

The number of leukocytes in the normal blood varies considerably. 
The average number, however, is between 6000 and 8000. Alterations 
in the number under various circumstances will be discussed later. 

Proportions of the Different Forms.- — The relative proportions. (" dif- 
ferential count") of the different leukocytes are determined by counting 
large numbers and calculating the percentage proportion of each form. 



DISEASES OF THE BLOOD 



435 



Approximately there are 20 to 30 per cent, lymphocytes, 60 to 70 per 
cent, polymorphonuclear forms (neutrophiles and eosinophils), 4 to 8 
per cent, transitional and large mononuclear. About 1 to 3 per cent, 
of all the leukocytes contain eosinophile granules, and occasionally a 
larger proportion is met with in normal blood. Not over 0.5 per cent, 
of the normal leukocytes are basophilic. 

Blood=plaques or Platelets. — These are small disks somewhat 
resembling the red corpuscles, though smaller and without the character- 
istic biconcavity of the latter. They contain a chromatic body and have 
been described as nucleated by some observers. They rarely exceed 
3 At in diameter, and are often much less. They are viscid, and tend to 
adhere to the other corpuscles or to become agglutinated in clusters. 
The total number has been estimated at from 150,000 to 500,000 per 
cubic millimeter. The origin of the platelets is still uncertain. Accord- 
ing to some they are derived from the erythrocytes by a process of ex- 
trusion from the cytoplasm of the latter; others have held that they are 
formed by the breaking down of leukocytes. Wright claims to have 
shown that they are products of the megakaryocytes of the bone-marrow. 

The plasma of the blood is an albuminous liquid containing mainly 
serum-albumin and serum-globulin and various saline compounds. The 
relative proportion of serum-globulin to serum-albumin is as 1 to 1 or 
1}^. Of the saline constituents, sodium salts are most important, the 
phosphates, carbonates, sulphates, and chlorids being most abundant. 
Various other nitrogenous and non-nitrogenous substances are present 
in small proportions. Reference will be made to some of these below. 

BLOOD FORMATION 

The process of blood formation is still a matter of uncertainty in 
some particulars. The prevailing opinion is that all of the blood-cor- 
pucles, erythrocytes and leukocytes, are derived from mesoblastic cells 
which become differentiated to form the lining endothelia of blood- 
vessels and lymphatics. From the former group the primitive cells 
which give rise to erythrocytes and the granular leukocytes take their 
origin; from the lymphatic endothelia are developed the primitive cells 
which originate the lymphocytic series. The earliest clearly differen- 
tiated blood-cell is a large hemoglobin-containing cell with pale nucleus, 
found in the mesoblastic columns in which the blood-vessels are differ- 
entiated. This is the primitive erythroblast. According to older investi- 
gators the erythroblasts were derived from this cell. More recent 
investigations, however, seem to show that this is but a temporary phase 
in fetal blood formation. Later, the endothelia of the blood-vessels give 
rise to (1) certain basophilic erythroblasts, containing no hemoglobin, 
from which the red cells are derived; and (2) myeloblasts from which 
the myelocytes and their derivatives take their origin. The lympho- 
cytic series, by a similar process of differentiation, is derived from the 
endothelia of lymphatic channels. 

During the earlier portion of fetal life the liver is the principal seat 
of blood formation; after the third month the spleen and bone-marrow 
participate, but the spleen ceases to be active somewhat before the end 
of fetal life and the liver shortly after birth. The lymphatic glands are 



436 



A TEXT-BOOK OF PATHOLOGY 



the chief source of lymphocytes in intra- and extra-uterine life. It is 
noteworthy that in many anemic conditions a return to fetal processes 
of blood formation is observed. 

PATHOLOGICAL CHANGES IN THE RED CORPUSCLES 

The size of the red corpuscles varies in diseases of different kinds. 
The term anisocytosis has been suggested for this irregularity. There 
may be dwarf corpuscles, 2 to 4 or 5 ju in diameter (microcytes) ; or, on 
the other hand, giant cells (megalocytes) , from 9 to 15 /x or even 20 ju in 
diameter. The small forms frequently have a spherical shape rather 
than the disk-like form of the normal corpuscle, and may be deeply 
pigmented. The large corpuscles are often irregular in shape, and are 
prone to be paler and more basic than normal corpuscles, and usually 
appear without the concavity of the normal cell. Some observers have 
found that the average size of the red corpuscle is greater in certain 
diseases than in health. This is sometimes the result of hydropic 
conditions. 

The shape of the corpuscles often suffers great change, and many 
forms of irregularity may be observed. The term poikilocytosis is ap- 
plied to this condition. Some of the poikilocytes may be exceedingly 
small and may present active movements. These have been termed 
"pseudobacilli" by Hayem. These changes of form in red corpuscles 
are regarded by many authorities to be the result of degenerative changes 
in the protoplasm with consequent ameboid movement which occasions 
irregular projections. The small forms are doubtless in many cases the 
result of fragmentation. Ehrlich used the term "schistocyte" to indi- 
cate this fact. 

Dust=corpuscles. — Muller described certain small spherical bodies 
somewhat resembling the leukocytic granules, but lying free in the 
plasma and often activity motile. These he termed hemokonice, or dust 
corpuscles. They occur in normal blood as well as in that of various 
diseases. A number of theories have been offered regarding the nature 
of these bodies. Some authors regard them as extruded leukocytic 
granules; others, as portions of protoplasm of the leukocytes. Our own 
belief is that they are fragments of red corpuscles, similar to those that 
may be produced by heating fresh blood under a cover-glass to destruc- 
tive temperatures. Under these circumstances small, bud-like processes 
are formed on the periphery of the red corpuscles, and some of these 
may break off and float free in the plasma. 

Visible ameboid movements may sometimes be observed under 
the microscope, especially in severe anemias, such as pernicious anemia. 

Nucleated Red Corpuscles, or Erythroblasts. — The red corpuscle 
when first formed is always nucleated, and throughout fetal life a dimin- 
ishing proportion of the erythrocytes remains so. At birth and through- 
out extra-uterine life the erythrocyte is non-nuclear. The loss of the 
nucleus was formerly attributed to a process of extrusion, but is now 
believed to be always due to pyknosis, karyorrhexis, and karyolysis 
within the cell. 

Nucleated erythrocytes occur in the severe anemias as in fetal blood. 
They are more frequent in the severest cases, and in particular in the 



DISEASES OF THE BLOOD 



437 



anemias of children. Some are exceedingly small (microblasts) , some 
about the size of the normal red corpuscle (normoblasts), and some large 
and irregular (megaloblasts) . The stained nucleus of the normoblast is 
darker and more compact than that of the megaloblast, and is often 
near the periphery of the cell or apparently partly extruded. The 
smaller forms appear first and in the more moderate anemias; occasion- 
ally they occur in great numbers or crops from time to time (blood crises). 
Degenerations of nucleated red corpuscles may occur, and very fre- 
quently are seen in the circulating ery throblast . The usual f orms are kary- 
olysis — solution of the chromatin; karyorrhexis — fragmentation of the 
nucleus ; and pyknosis — clumping or condensation of the nuclear structure. 
Granular degeneration, vacuolation, and nuclear atrophy also occur. 

Howell-Jolly bodies are small round bodies sharply differentiated from 
the protoplasm of erythrocytes and staining like the chromatin of nuclei. 
They seem to be undoubtedly nuclear remains and have been found in 
various types of anemia, occurring in otherwise normal red cells or by 
the side of the nucleus of erythroblasts. 

Karyokinetic figures are occasionally seen in the nuclei of erythro- 
blasts, in pernicious anemia, in leukemia, in dibothriocephalus anemia, 
and in certain anemias of children. 

Shadow corpuscles are red corpuscles that have lost their color 
almost completely and are scarcely visible. They may be observed in 
severe anemias, and especially in cases of intoxication with blood- 
poisons. 

Ring Bodies. — Cabot, by means of Wright's modification of Irish- 
man's stain, has demonstrated in the red cells of anemic blood the 
presence of ring bodies, which he is inclined to believe represent the 
remains of a previously existing nucleus. They were found in 3 cases 
of pernicious anemia, 3 of lead-poisoning, and 1 of lymphatic leukemia, 
in all of which normoblasts were also found. The rings appear to be 
made up of a series of granules in some cells; in others, of a continuous 
line. They usually stain red, though blue is not uncommon. 

Polychromatophilia. — The normal red corpuscle has a special 
affinity for acid stains. In anemic conditions certain erythrocytes show 
a distinct affinity for basic stains when stained with mixtures of acid and 
basic dyes. Thus in staining with eosin and hematoxylin the 
affected corpuscles may present a purplish or violet color, instead of a pink. 
This altered staining reaction seems to occur in "young" cells and to be 
most pronounced where increased and perhaps pathological marrow acti- 
vity is present. 

Vacuolation and pigmentation of the red corpuscles are rare forms 
of degeneration. The pigmentation is due to separation of the hemo- 
globin in the form of irregular granules. 

Basic granulation is a form of degeneration in which minute or 
rather coarse granules that stain with certain basic stains are found in 
the substance of the red corpuscles. The number of granules in the 
cell may be small or large; the cell may be otherwise little altered; it 
may be polychromatophilic. The condition has been found in various 
diseases, such as leukemia, pernicious anemia, and malaria, but is most 
frequent in lead-poisoning. Some observers, by using certain special 



438 



A TEXT-BOOK OF PATHOLOGY 



staining methods, claim that the basic granules are nuclear fragments 
and regard the process as regenerative rather than a degeneration. It 
is very probable, however, that the granules seen in these studies have 
not been those now under discussion. 

Alterations of Isotonicity. — All forms of cells have certain osmotic 
relations, in consequence of which they retain their constituent elements 
in the presence of surrounding liquids of certain osmotic tension. If the 
osmotic relations vary or the surrounding liquids are altered, the consti- 
tuents of the cell may be extruded. In the case of blood-corpuscles 
distilled water rapidly abstracts the hemoglobin and other substances, 
but saline solutions of certain strengths do not so affect the corpuscle. 
The exact strength of a certain saline solution may be determined which 
will preserve the corpuscle, and this is known as the isotonic strength of 
the corpuscle expressed in percentage terms of the saline used. Degen- 
erated corpuscles more readily yield their constituents, and the isotonic 
saline solution is, therefore, of higher percentage. In normal blood the 
isotonicity of the red corpuscle is generally 0.46 to 0.48 per cent. NaCl; 
that is, in solutions of common salt of this strength the red corpuscles 
hold their hemoglobin. In certain anemic diseases the isotonic strength 
of salt solution may be from 0.5 to 0.6 per cent., but often, on the con- 
trary, solutions from 0.40 to 0.44 per cent, may be isotonic. 

PATHOLOGICAL CHANGES IN THE LEUKOCYTES 

Very frequently degenerations of the nuclei of the leukocytes are 
observed in the form of fragmentations or karyolytic change. Atten- 
tion has been called (Neusser) to the presence of basophilic granules 
about the nucleus in certain forms of disease, such as leukemia, gout, 
and lithemia in its widest sense. These granules are supposed to be sig- 
nificant of disintegration of the nuclei in the process of uric-acid forma- 
tion. Their nature and significance, however, are unsettled. Occasion- 
ally vacuolization and fatty degeneration of leukocytes are observed, 
and sometimes, as in infectious fevers and in suppuration, glycogen may 
be found in abnormal quantities. In cover-glass preparations the leuko- 
cytes are sometimes found broken or fragmented; or fenestrated, basket- 
like, pale-staining forms are seen. The latter doubtless occur to some 
extent in the circulating blood and are frequently spoken of as " leuko- 
cytic shadows." 

Iodophilia.- — This term is applied to a condition of the blood in 
which there are found in the leukocytes or the plasma granules that 
stain with iodin, like glycogen. The term " glycogenic reaction" was 
formerly applied, though recently some doubt has arisen as to the 
glycogenic nature of the granules in question. The leukocytes involved 
in this form of granulation are chiefly the polymorphonuclear. Baso- 
philic leukocytes may be affected, but never the eosinophiles. The 
intracellular material is found in the form of small granules of regular 
shape and size, which stain a yellowish-red or brown color with iodin. 
Less commonly the leukocytes may be diffusely stained, the granules 
being wanting or so small as to be indistinguishable as granules. The 
extracorpuscular granules are found in more advanced cases. They 
resemble the intracorpuscular granules in appearance. 



DISEASES OF THE BLOOD 



439 



The significance of iodophilia has not been positively determined. 
The condition is found in association with leukocytosis or less commonly 
in the absence of leukocytosis, but it bears no quantitative relation to 
the degree of leukocytosis. It has been found in various forms of tox- 
emia, in grave anemias due to loss of blood or to other causes, in fevers, 
and in various other conditions. 

The blood-film, without previous fixation, is stained with iodin and 
iodid of potash in a gum-arabic solution. 

PATHOLOGICAL CHANGES IN THE PLASMA 

Various disorders of the plasma have been studied. These are 
mainly of a chemical sort, and consist of the presence of abnormal sub- 
stances or of normal constituents in excessive quantity. Urea and other 
nitrogenous bodies are present in large quantities in some cases of ne- 
phritis and uremia. Uric acid occurs in small quantities in health ; but 
in larger quantities in gout, lead poisoning, leukemia, in some forms of 
leukocytosis, and during resolution of pneumonia. Sugar is found in 
excessive quantities in diabetes, in cases of high blood-pressure, in thy- 
roid diseases, and, according to some observations, in cases of carcinoma. 
Levulose and other carbohydrates are rare constituents of the plasma. 
Fatty acids may be present in leukemia, diabetes, acute yellow atrophy 
of the liver, and some other diseases. 

The plasma retains its albuminous composition with much tenacity 
in the presence of severe disease or starvation and also its inorganic con- 
stituents, especially sodium chloride. Reference has been made in the 
discussion of Acidosis to the loss of sodium and to the consequent loss in 
the power of the blood to carry C0 2 . The presence of toxic substances 
in the blood plasma, the result of bacterial action is referred to in the dis- 
cussion of bacteria. 

Hypertonicity oj the serum is a term indicating that the salinity of 
the plasma or serum is such that the blood may be somewhat diluted 
without destruction of the corpuscles. By graduated dilutions the de- 
gree of hypertonicity may be estimated, and is found less in certain 
diseases than in health. (See Isotonicity of the Red Corpuscles.) 

Hyperinosis and hypinosis are terms designating increased and de- 
creased capability for fibrin formation. The former is met with at 
times in chlorosis, leukemia or other anemic affections, and in certain 
infectious diseases. The latter is notably present in leukemia, perni- 
cious anemia, and some cases of hemolysis. There has been much 
theorizing in regard to these conditions, but very little knowledge of 
practical importance has been acquired. 

PLETHORA 

r This is the name applied by the older writers to a condition in which 
the total quantity of blood was supposed to be excessive. It is now 
recognized that plethora is much less frequent and permanent than was 
formerly believed Several varieties were described. 

Plethora vera was the name given to the condition in which the 
quantity of the blood was supposed to be increased without change in 
its quality. Persons supposed to have this condition are described as 



440 



A TEXT-BOOK OF PATHOLOGY 



robust, with high color and vigorous circulation. They are generally 
individuals living in luxury. The term " full-blooded" is still applied, 
but it is recognized that the fulness of the superficial vessels is the result 
of peculiarities of the circulation rather than of increase in the quantity 
of blood. 

Plethora apocoptica is the term given to conditions in which there is 
local increase in the blood. 

Plethora hydremica is a condition in which the total quantity of the 
blood is increased by dilution. This was regarded as frequent in cases 
of cachexia, after hemorrhages, etc. 

Experimental evidence might be referred to to substantiate the view 
that plethora in the strict sense does not often occur as a lasting condi- 
tion. Temporary plethora is produced by the drinking of large quanti- 
ties of liquid, but the excretory organs soon dispose of this excess. 

OLIGEMIA 

This is a term indicating reduction in the quantity of blood. This 
is met with temporarily after hemorrhage, but very soon serous liquid 
from the tissues enters the blood-vessels and restores the original quan- 
tity. At the time of the hemorrhage the quantity may be immediately 
reduced to a very great degree without causing death. Serious conse- 
quences are averted by the activity of the vasomotor system, the blood- 
vessels accommodating themselves by contraction to the reduced quantity 
of blood. Subsequently when liquid of the tissues is absorbed into 
the blood-vessels the latter dilate and their natural volume is soon re- 
stored. The blood, however, becomes hydremic, or watery. Oligemia 
or quantitative anemia may possibly occur in certain cachectic and 
anemic diseases, but this has not been proved, and the relative propor- 
tion between the mass of blood and the weight of the body is certainly 
not much disturbed in any case. 

llie possibility that rapid loss of fluid from the blood vessels and 
consequent reduction in the volume of blood may be an important 
factor in the pathology of shock has been much discussed (see " Shock"). 

HYDREMIA AND ANHYDREMIA 
Hydremia, a diluted or watery condition of the blood, may occur 
from excessive consumption of water, but active excretion of liquid 
soon restores the blood to its previous condition. Hemorrhage leads to 
hydremia in the manner above described; and in the chronic anemias 
there is possibly some dilution of the serum. It has never been shown, 
however, in any of the many experiments made to determine this point 
that the plasma in anemias is less rich in solid consituents than normal 
plasma. The reduction in solid matter in the blood as a whole is due to 
the diminution in the number of red corpuscles and changes in their 
composition. 

Anhydremia is a condition in which the plasma of the blood is 
thickened by the loss of watery elements. This may occur in con- 
sequence of excessive sweating or excessive discharge of water from the 
bowels, kidneys, etc. The number of red corpuscles in a given bulk of 
blood increases. The specific gravity and the solid residue of the blood 
as a whole increase correspondingly. 



DISEASES OF THE BLOOD 



441 



LIPEMIA 

This is a pathologic condition in which fat occurs free in the blood- 
plasma. Fat is always present as a normal constituent of blood, and 
is in slight excess during the process of digestion. Lipemia occurs in 
cases of chronic nephritis, diabetes, pulmonary tuberculosis, alcohol- 
ism, and some 'other conditions, and may reach marked grades of sever- 
ity. The blood may have a milky appearance to the naked eye, and 
under the microscope highly refractive droplets or granules are observed. 
The latter stain black with osmic acid (Fig. 190). 




Fig. 190. — Blood from a case of lipemia, stained with osmic acid : upper half of field 
cleared with oil of turpentine; lower half shows the fat-droplets and granules stained 
with osmic acid between the blood-corpuscles; enlargement, 100 diameters (after Gum- 
precht; Deutsch. med Woch., Sept. 27, 1894). 

The appearance of fat in the blood is ascribed by some to an altera- 
tion in its character when being transported and to a decrease in tissue 
and blood lipase. It may appear in conditions of reduced nutrition 
when the fat is transferred from fat depots to other situations for meta- 
bolic use. 

MELANEMIA 

This condition is distinguished by the occurrence of dark pigment 
or granular matter in the circulating blood. It occurs in cases of malaria 
and certain other fevers. The pigment may be free in the plasma in the 
form of yellowish or blackish granules; or may be found as small par- 
ticles in the leukocytes. 

HEMOCYTOLYSIS— HEMOGLOBINEMIA 

Definition. — Hemocytolysis is the term applied to the conditions 
in which the red blood-corpuscles are destroyed. The name hemolysis 
is generally employed in the same sense, though strictly speaking it 



442 



A TEXT-BOOK OF PATHOLOGY 



refers to destruction of all of the elements of the blood. In this condition 
hemoglobin is liberated and is dissolved in the plasma. To this the term 
" hemoglobinuria" is applicable, but the name "methemoglobinemia" 
is more appropriate, as the hemoglobin is usually present in the serum 
in this altered form. 

Etiology. — Hemolysis constantly takes place in the liver, the 
coloring-matter of the blood being converted into bile-pigments. Path- 
ological hemolysis results from the action of various infectious and toxic 
agents. It occurs in the course of severe malaria, relapsing fever, pneu- 
monia, and various hemorrhagic infections; and is occasioned by many 
poisons (see Blood-poisons). Excessive cold may be a contributing 
cause, as seems to be the case in some instances of paroxysmal hemo- 
globinuria (q. v.). 

The serum of certain animals has more or less hemolytic effect when 
injected into other animals. By repeated injections the serum of the 
animal under experiment may acquire hemolytic properties. Anti- 
hemolysins have also been produced in experimental investigations and 
promise to be of practical use, as in the case of certain hemolytic venoms. 
The explanation of hemolysis elaborated by Ehrlich and later con- 
firmed by Flexner and Noguchi is referred to in the section on Immunity. 

Pathological Anatomy. — The blood may present striking morpho- 
logical changes in the red corpuscles, such as microcytosis, megalocytosis, 
poikilocytosis, fragmentation, and vacuolation. Shadow corpuscles may 
be abundant, and in the later stages of the process beginning regeneration 
of the blood causes the presence of nucleated red corpuscles. The blood 
as a whole is often dark in color. 

Associated changes are frequently met with in the liver, kidneys, 
and skin. The hepatic cells are often swollen and more or less degener- 
ated and bile stained. Excessive production of bile (polycholia) may 
occur. This overproduction, with the swelling of the hepatic cells and 
the consequent obstruction of the biliary channels, occasions reab- 
sorption of bile and consequent jaundice (so-called " hematogenous jaun- 
dice"). The excess of hemoglobin, which cannot be disposed of by the 
liver, may be excreted in the urine (hemoglobinuria). Sometimes 
hemoglobin infarcts are met with in the renal tubules; and thrombosis 
of the renal or other blood-vessels is occasionally observed. Acute 
nephritis is a rare result. 

Pathological Physiology. — Hemocytolysis leads to more or less 
pronounced disturbance of the internal or tissue respiration, as the al- 
tered hemoglobin is incapable of carrying oxygen. Dyspnea and various 
nervous symptoms are the result. The liberation of cellular constituents 
(from destruction of the red and white corpuscles) occasions increased 
coagulability of the blood and the formation of thrombi in arterioles 
and capillaries. Fever and other general symptoms may be due to 
the same cause (ferment intoxication). 

POLYCYTHEMIA 

Polycythemia, or erythrocytosis, is a condition in which the number 
of red corpuscles in a given bulk of blood is increased. It is met with 
in a variety of conditions, including certain cardiac diseases with slow 



DISEASES OF THE BLOOD 



443 



failure of compensation, and especially in congenital cyanosis; in car- 
bon-monoxid poisoning and other forms of cyanosis; in residents of high 
altitudes; in the newborn; and in cases of cholera or other diseases in 
which liquid discharges cause inspissation of the blood. The explana- 
tion of the increased number of corpuscles in some of these conditions 
has occasioned considerable controversy. It is manifestly possible 
that erythrocytosis may be relative when the number of corpuscles is not 
actually increased, but their proportion in a given bulk of blood en- 
hanced by diminution in the amount of plasma; or actual when there- is 
an increase in the total number of red cells in the body. It does not 
seem probable that relative erythrocytosis could have more than a 
brief duration, as in cases of cholera. It is possible, however, that in 
certain conditions in which the peripheral circulation is stagnant the 
number of corpuscles in a given bulk of blood drawn from the finger or 
ear might be relatively increased, without any actual general erythrocy- 
tosis. The higher count of red corpuscles in the blood of dependent 
parts or in a finger congested by constriction or cold lends some color 
to this view. Recent investigators tend toward the opinion that lasting 
erythrocytosis is an evidence either of stimulation of the bone-marrow, 
as a result of conditions which interfere with oxidation, or of abnormal 
conditons of the spleen. The association of marked splenic enlargement 
is some cases is cited as evidence of the latter view; but convincing proof 
of the relationship is lacking. 

Polycythemia with Chronic Cyanosis and Enlarged Spleen. — A 
clinical entity comprising these symptoms, together with weakness, 
prostration, and vertigo, has recently been recognized. No explanation 
has thus far been given for this condition. In some cases the spleen 
was found to be tuberculous; in others only chronic hyperplasia was 
found. 

Besides the conditions before referred to as causing cyanosis and 
polycythemia, certain pulmonary diseases, such as emphysema and 
chronic poisoning with coal-tar products, such as acetanilid and anti- 
pyrin, must be recalled. In some of these cases the spleen may be 
enlarged and the condition may simulate the one just under considera- 
tion. In the reported cases of chronic cyanosis with polycythemia, 
however, these causes of the polycythemia and cyanosis as well as the 
ones before referred to are wanting. 

LEUKOCYTOSIS 

The term " leukocytosis'' is given to a more or less transient, but ex- 
ceptionally chronic, increase in the number of leukocytes, under the 
stimulus of a foreign agent, bacterial or toxic, or of diseases outside 
the blood-making organs. The terms " polymorphonuclear leuko- 
cytosis," "lymphemia," "eosinophilia," and "myelocythemia" are used 
to designate increase of the polymorphonuclear leukocytes, lympho- 
cytes, eosinophils, and myeloid elements respectively. 

Etiology. — The causes of leukocytosis are varied. An excessive num- 
ber of leukoctyes in comparison with the figures found in adults is gen- 
erally observed as a normal condition in the newborn, the number of 
corpuscles remaining in slight excess during the first year of life. "Phys- 



444 



A TEXT-BOOK OF PATHOLOGY 



iologic leukocytosis" also occurs in many cases of pregnancy; and is 
quite constant during the period of digestion in healthy persons, protein 
food being more striking in the effect than a farinaceous or mixed diet. 
In some diseases of the stomach postdigestive leukocytosis seems not 
to occu . 

Inflammatory and Infectious Leukocytosis. — Among the strictly 
pathological forms of leukocytosis the most important are those due 
to inflammations and infections of various kinds. Croupous pneu- 
monia occasions considerable increase of leukocytes in most cases, and 
this is continuous until the final decline of the fever. Suppurations of 
all kinds act in a similar manner. Inflammations of the serous mem- 
branes — peritonitis, pleurisy, meningitis — may be attended by moderate 
or severe leukocytosis. Among the acute infectious fevers there are 
some in which leukocytosis occurs and others in which this is wanting, 
and this fact often proves valuable to the clinician. Among those in 
which the leukocytes do not increase in number are typhoid fever, in- 
fluenza, malaria, and acute miliary tuberculosis. 

Cachectic leukocytosis occurs in a variety of marantic conditions, 
and toward the end of life in any case of wasting disease there may be a 
great increase in the number of leukocytes. This agonal or terminal 
leukocytosis is either cachectic (toxic) in nature or it may be due to 
terminal infections. 

Malignant tumors frequently cause leukocytosis. 

Hemorrhage may occasion increase in the number of white corpuscles, 
more or less proportioned to the quantity of blood lost. 

Mechanical and Thermal Causes. — Massage and cold baths fre- 
quently cause increase in the number of leukocytes for a time. 

Medicinal leukocytosis, or that due to the introduction of various 
drugs, is probably allied to infectious and cachectic leukocytosis in the 
manner of its production. 

Pathogenesis. — The nature of leukocytosis has been the subject of 
much controversy. The earliest view regarding the pathogenesis of 
leukocytosis was that in some manner excessive production of leuko- 
cytes took place either in the blood or elsewhere. Later some investiga- 
tors claimed that there was evidence that the leukocytes were not de- 
stroyed as rapidly as in health. Still later the presence of che'motactic 
substances, positive or negative, in the blood was regarded as the cause 
of increase or decrease of leukocytes. At present it seems correct to 
interpret leukocytosis as a reaction of the blood-making tissues to 
agents which stimulate them to overactivity. Such influence is most 
frequently manifested in the bone-marrow (which occasions the preva- 
lent type of leukocytosis — polymorphonuclear), but sometimes the 
lymphatic glands are principally affected and lymphemia results. 

Dormant myeloid elements in the spleen or elsewhere may be stim- 
ulated to activity and may play a considerable part in the development 
of leukocytosis. This is more likely to be the case in more chronic 
types. 

According to present conceptions, the explanation of leukocytosis on 
the basis of chemotactic effects of circulating toxic agents, the blood- 
making organs being only passive participants, must be abandoned. 



DISEASES OF THE BLOOD 



445 



As a reaction on the part of blood-making tissues is the important 
feature in the process, it follows that toxic agents too feeble to excite 
such reaction may fail to produce leukocytosis; and overactive irritants 
may have a paralyzing effect. 

Character of the Blood. — The blood in leukocytosis varies consider- 
ably in character. The number of leukocytes may be only moderately 
increased (10,000 to 20,000) or may be excessive (50,000 to 100,000). 

In the majority of cases of leukocytosis the polymorphonuclear 
elements are in relative as well as actual excess, the mononuclear ele- 
ments being actually increased in number, but relatively deficient. 
The proportion of polymorphonuclear elements is frequently 80 to 85 
per cent., and sometimes 90 or 95 per cent., instead of 65 to 70 per cent. 
In the leukocytoses following hemorrhage, in cachectic leukocytosis, 
in septic leukocytoses, and in that due to malignant tumors the poly- 
morphonuclear cells are usually increased, while in the leukocytosis 
of the newborn and early childhood and in association with some tumors, 
especially lymphomata, the mononuclear elements predominate. Lym- 
phemia is occasionally met with in infections in which ordinarily poly- 
morphonuclear leukocytosis would occur. Some unknown factor, 
perhaps individual, operates in such cases. Lymphemia is also observed 
in pertussis, syphilis, typhoid fever, and scarlatina. Eosinophilia has 
been observed in a variety of skin disease, in animal parasitism, especially 
trichinosis, in anaphylaxis, asthma, etc. Myelocythemia has been 
found in various severe infections (notably in unfavorable cases of diph- 
theria) and in cases of metastasis of tumors to the bone-marrow. It 
is often pronounced in the so-called pseudoleukemia infantum. 

Pathological Physiology. — Leukocytosis certainly exercises some 
profound influence upon the system, but the exact nature of this influence 
is unsettled. Those who contend in favor of the phagocytic theory of 
immunity claim, more or less directly, that the increase of leukocytes 
is a protective process, the purpose being the removal and destruction of 
irritants. This view seems to have gained ground with increased 
knowledge of the mechanism of infection. Others believe that leuko- 
cytosis is part of the cellular processes concerned in the production of 
immunizing substances. There is certainly more active destruction of 
leukocytes in leukocytosis than in health, as is evidenced by the increase 
of xanthin bases and uric acid in the urine; and it may be that in this 
destruction protective substances are liberated. 

LEUKOPENIA 

This is a condition in which there is deficiency in the number of 
leukocytes. This is met with in moderate degree in various diseases, 
such as tuberculosis, typhoid fever, some cases of cachexia, inanition, 
splenomegaly, progressive pernicious anemia, etc. The nature of the 
condition is not entirely clear. Some have held that it is due to destruc- 
tion of leukocytes (leukolysis), while others claim that it is the result 
of altered distribution of the leukocytes. It has been shown by experi- 
menters that the injection of certain micro-organisms or toxic sub- 
stances may produce, first, a decrease in the number of leukocytes, and 
then an increase. The primary leukopenia is explained by some as the 



446 



A TEXT-BOOK OF PATHOLOGY 



result of active destruction of leukocytes, but the conditions of the 
urine do not give evidence of such active destruction, and others have 
shown that the capillaries of the lungs, liver, and other organs are over- 
filled with leukocytes during this stage. The assumption, therefore, 
seemed warranted that leukopenia might result from disturbance in the 
distribution of the leukocytes. 

According to more modern conceptions, however, leukopenia may be 
regarded as a result of unfavorable action upon the blood-making tis- 
sues by toxic agents. 

• ANEMIA 

Definition. — This term includes a variety of conditions in which 
the blood is reduced in quality in one constituent or another. The term 
oligocythemia indicates a reduction in the number of red corpuscles, 
while the name oligochromemia indicates a reduction in the coloring- 
matter of the corpuscles. Usually these conditions are associated. 

Classification of Anemias. — It is not as yet possible to offer a 
strictly scientific classification, but for ordinary purposes the old division 
into primary and secondary anemias may be retained. The term ' ' primary 
anemia" may be given to forms in which the anemia is the striking path- 
ological condition. The older writers used the name to indicate that the 
anemia was an essential disease of the blood itself and dependent upon 
no preceding affection, excepting possibly a disturbance of the hemato- 
poietic organs. The term " secondary anemia," or " symptomatic 
anemia," may be used to designate anemic conditions in which some 
underlying disease that has occasioned the anemia is conspicuous. Ac- 
cording to the classification here offered, all anemias are recognized as 
secondary in the strict sense, but those in which the underlying disease 
is not conspicuous are classified as primary, and those in which the orig- 
inal disease is conspicuous as secondary. Another aspect of the matter, 
within the terms of the definition, is that in the diseases classified as 
primary, the effects of the original condition, whether toxemia, infection, 
or of other sorts, are manifested most strikingly in the blood-making 
apparatus. In the secondary anemias such effects are subsidiary in 
importance and relatively inconspicuous. 

THE SECONDARY ANEMIAS 

Etiology. — Various unsanitary conditions may influence the char- 
acter of the blood by the constant disturbance of the organic functions. 
A cause of immediate anemia is hemorrhage. This first leads to reduc- 
tion in the quantity of blood; and later by absorption of liquid from the 
tissues to dilution of the blood, or hydremia. Finally, after a variable 
period, the character of the blood is restored by regeneration of cor- 
puscles and of coloring-matter. Parasites of various sorts may lead 
to anemia. Among the more important are the intestinal worms, 
Uncinaria duodenalis, Dibothriocephalus latus, and Anguillula intes- 
tinalis. The mode of action of these is not entirely clear. Some have 
held that they cause anemia by loss of blood through the intestine, and 
this is probably true in the case of Anguillula and Uncinaria, but marked 
anemia may occur from the presence of Bothriocephalus, which is not 



DISEASES OF THE BLOOD 447 

a blood-sucker and does not occasion hemorrhage. An explanation 
worthy of consideration in these cases is that the parasites generate 
poisons either in their ordinary life or by their death and decomposi- 
tion, and that these poisons are the cause of the anemia. Recent in- 
vestigations seem to indicate that certain lipoids are the direct hemolytic 
cause of the anemia in cases of bothriocephalus invasion. Other in- 
testinal parasites may occasion more or less anemia directly or indi- 
rectly. The parasites occurring in the blood itself, notably the malarial 
organism, may cause extreme anemia. Infectious diseases, especially 
streptococcus infections, frequently lead to impoverishment of the 
blood. In the acute febrile diseases, such as typhoid fever, rheumatism, 
and pneumonia, the anemia may not be conspicuous during the progress 
of the disease, but becomes apparent after the fever has subsided. 
This may be explained by the assumption that increased respiration 
and sweating cause inspissation of the blood and relative increase 
in the number of red corpuscles during the existence of fever, so that 
the anemia is unnoticed. In chronic infections, such as syphilis and 
tuberculosis, marked anemia may occur. Among the poisons capable of 
producing anemia are lead, arsenic, phosphorus, and other metallic sub- 
stances, and experimentally pyrogallol, nitrobenzene, pyrodin, and various 
coal-tar products have been used to produce anemia. Various nitro- 
and amido compounds produced in the manufacture of dyes and explosives, 
such as trinitrotoluene, dinitrobenzene etc. may occasion high grades of 
anemia and have become clinical causes of importance as the industries in 
which they are employed have become numerous and diversified. The 
anemias of various infectious diseases are undoubtedly toxic in character, 
and very probably those occurring in gastro-intestinal and nutritional 
diseases are similarly the result of the action of poisons generated within 
the body. Organic diseases and new growths of various sorts may occasion 
anemia by the general disturbance of health, by toxic products gener- 
ated in the course of disease, or by hemorrhage. 

Pathological Anatomy. — The condition of the blood in secondary 
anemias varies with the duration and grade of the anemia. In moderate 
cases the number of red corpuscles decreases slightly (4,000,000 to 
3,000,000), and the hemoglobin is usually somewhat more reduced than 
the corpuscles. The fresh blood may show no visible changes under the 
microscope, and even in stained preparations the appearance may be 
normal. More marked anemia is distinguished by greater reduction, 
the number of corpuscles sinking to 2,500,000 or 2,000,000 per cubic 
millimeter in extreme cases. The color index remains low. Examina- 
tion of the fresh blood shows pallor of the corpuscles and various irregu- 
larities in size (microcytes and megalocytes) and shape (poikilocytes) . 
Nucleated red corpuscles may be present in small numbers, normo- 
blasts predominating. The stained blood may show the presence of 
polychromatophilic forms though this is not often pronounced. The 
leukocytes are usually in slight excess, the number depending very largely 
upon the cause of the secondary anemia. In post-hemorrhagic anemias 
moderate leukocytosis is the rule; in infectious anemias there may be very 
pronounced leukocytosis with especial participation of the polymorpho- 
nuclear neutrophiles. ^In some of the toxic anemias particularly in certain 



448 



A TEXT-BOOK OF PATHOLOGY 



aniline poisonings there may be distinct leukopenia with predominence 
of mononuclear forms, probably the result of severe damage of the bone 
marrow. Occasionally in severe secondary anemias myelocytes are present. 

Associated changes in various organs may be met with. Among these 
are parenchymatous and fatty degeneration of the heart, kidneys, and 
liver. These conditions have often been ascribed to reduced oxidation, 
which was supposed to be due to poverty in hemoglobin. Physiological 
studies, however, do not establish the existence of a reduction in the 
respiratory exchange of gases. It is likely that toxic conditions of the 
blood occur in anemia, and that the posions act directly upon the 
affected organs. 

Severe and long standing secondary anemias may present excessively 
low counts of red cells (1,000,000 or less) and in these cases, particularly 
the prolonged types, the color index may be more nearly normal or even 
above normal. At the same time the leukocytes may diminish and may fall 
to less than a normal number while the differential count may show a 
relative excess of mononuclear elements. These changes in the type of 
the anemia may perhaps be due to an exhaustion of bone marrow function 
and at this stage the anemia might be regarded as a chronic aplastic type 
(see Aplastic Anemia). The features above referred to, combined with 
changes in size and shape of the red corpuscles and some polychrom- 
atrophilia with perhaps the presence of a few erythroblasts, make up a 
picture that bears a puzzling resemblance to pernicious anemia. The 
differentiation is sometimes far from easy. 

The extreme anemias caused by poisoning with aniline and benzol 
derivatives likewise give evidence of damaged marrow function (leuko- 
penia, relative lymphocytosis) and at the same time exhibit features 
(jaundice, urobilinuria) indicating decided hemocytolysis. This com- 
bination of conditions also occasions a resemblance to pernicious anemia. 

Pathological Physiology. — -The process of oxidation is of particular 
interest in anemia, and, as has been stated, recent investigations show 
that the consumption of oxygen and elimination of carbon dioxide are 
normal. To accomplish this result more active circulation and greater 
energy of the tissues are required. Partly in consequence of the latter, 
diseases of the organs named in the last paragraph result; and at the 
same time some of the characteristic symptoms (palpitations, dyspnea) 
are produced. . In severe secondary anemias increased tissue-waste oc- 
curs, and nitrogen is discharged in excess of that ingested. 

THE PRIMARY ANEMIAS 

The principal conditions included under this title are chlorosis, 
progressive pernicious anemia, leukemia, and Hodgkin's disease. The 
modern tendency is to discuss the last two apart from anemias; but not 
only established custom, but the involvement of blood-making organs 
and the occurrence of actual anemia in' these diseases j ustify the classi- 
fication adhered to. The term simple primary anemia is sometimes used 
to designate a form of anemia without distinct cause, and characterized 
by moderate oligocythemia. There are, it is true, occasional cases of 
moderate anemia in which no definite precedent disease can be discov- 
ered; but these are exceptional cases, and are to be considered as second- 



DISEASES OF THE BLOOD 



449 



ary anemias in which the underlying disease is latent. Cases of this 
sort do not conform to a definite type, and cannot, therefore, be con- 
sidered as illustrating a special form of anemia. Another term fre- 
quently used is splenic anemia. This is even less satisfactorily defined. 
Splenic enlargement may occur in any of the primary anemias, and may 
in some cases be excessive. Moreover, some of the distinctly secondary 
anemias (as those of rickets, syphilis, and malaria) are very often 
attended with splenic enlargement. There is a group of conditions 
properly included under the title splenomegaly in which more or 
less anemia may occur, but this title rather than splenic anemia is 
preferable. 

CHLOROSIS 

Definition. — Chlorosis is a primary anemia due to retarded hemo- 
genesis, characterized by a peculiar pallor and marked reduction in the 
percentage of hemoglobin, and occurring almost exclusively in young- 
girls and women. 

Etiology. — Chlorosis is most frequent at the time of beginning men- 
struation and during the years immediately following this. A form of 
late chlorosis has been described in women above thirty years of age 
and at the menopause ; but the nature of this is doubtful. Chlorosis in the 
male is still more doubtful, though a few cases have been described by 
competent observers. Hereditary tendencies are of etiological impor- 
tance. The disease occurs more frequently in familes in which tuber- 
culosis is common than in those not so affected. Constitutional 
predisposition is also an important factor, poorly developed girls, and par- 
ticularly those of delicate mould, being especially liable to the disease. 
Virchow found hypoplasia of the heart and great vessels, and Rokitansky 
the same condition in the generative organs, and pathologists have been 
inclined to regard these as important factors in the development of the 
disease. 

Various exciting causes have been considered as of more or less 
importance. Emotional excitement was regarded as a prime cause by 
ancient authorities, and in consequence such terms as icterus seu febris 
amantium were applied. Home-sickness, grief, etc., are causes of 
moment. Intestinal auto-intoxication has been regarded as the essen- 
tial factor by many, but physiological chemists fail to find evidences of 
the existence of such intoxication. Menstrual disturbances are im- 
portant as symptoms, and have often been regarded as causes. The 
hypoplasia of the genital organs adds some probability to this view, 
but more definite evidence is wanting. Von Noorden strongly ad- 
vocates a theory that chlorosis is due to a failure of the internal secre- 
tion of the ovaries. 

At the present time it seems most likely that chlorosis is due to 
faulty development, and especially to a want of proper hemogenetic 
power. 

Pathological Anatomy.— The hypoplasia of the vascular and gener- 
ative systems has been referred to. These are primary lesions, and 
possibly causal. Various secondary diseases may be encountered, as in 
other anemias. Among these, myocardiac degeneration and dilatation 

29 



450 



A TEXT-BOOK OF PATHOLOGY 



are most important, though they do not attain high grades of severity. 
The spleen is frequently a little enlarged. Peculiar yellowish or greenish 
pigmentation of the skin is a striking feature. The pigment is doubtless 
altered hemoglobin, but its exact nature is unknown. 

The blood is paler than normal and watery. The specific gravity 
decreases progressively, and the solid matter is deficient. Increased 
coagulability is sometimes observed. The number of red corpuscles 
may be normal, even in well-developed cases, but the proportion of 
hemoglobin sinks progressively. In prolonged cases the corpuscles 
become reduced in number, but the deficiency of hemoglobin continues 
to be excessive. Severe cases of chlorosis frequently show 3,000,000 or 
2,000,000 red corpuscles per cubic millimeter and 30 to 20 per cent, of 
hemoglobin. The red corpuscles may be little altered in appearance 
in the early staggs; later, great gallor of the cells, and irregularities in 
size and shape are frequent, nucleated red corpuscles (especially normo- 
blasts) make their appearance. The latter sometimes occur in great 
numbers in crops (blood crises). The leukocytes are usually normal 
in number and kind; but in some cases myelocytes have been met 
with. 

During the process of recovery from chlorosis the red corpuscles 
increase in number before any change occurs in the percentage of hemo- 
globin. 

The conditions of the blood in chlorosis do not differ greatly from 
those found in certain secondary anemias and there is little doubt 
that many cases regarded as chlorosis belong in the latter group. It is 
a notable fact that clinicians recognize true cases of chlorosis less and less 
frequently. 

Pathological Physiology. — Chlorosis resembles the secondary ane- 
mias in most particulars, as far as its influence on the general health is 
concerned. Some of the symptoms (cardiac and menstrual) are doubt- 
less due to primary abnormalities of structure. The preservation of the 
subcutaneous fat despite advancing anemia is a striking feature. It 
is explained by von Noorden on the assumption that the quiet and 
warmth which chlorotics find necessary to their comfort lead to accumu- 
lation of fat. Decreased oxidation is certainly not the cause. 

PROGRESSIVE PERNICIOUS ANEMIA 

Definition. — Progressive pernicious anemia is a form of hemolytic 

anemia characterized by certain hematologic features significant of 
pathological activity of the bone-marrow. It is probably always fatal, 
though a few instances of recovery have been reported by competent 
authorities. An exact definition and a positive clinical differentiation 
from certain other conditions are not possible. Thus in certain cases 
of tertiary syphilis, carcinoma and diseases of the spleen, hemolytic 
anemia scarcely if at all distinguishable from pernicious anemia may occur. 

Etiology and Pathogenesis. — The disease was first described by 
Addison as a wholly causeless anemia, that is, an anemia independent 
of preceding disease of any sort. Subsequent investigation seemed to 
show that it might be secondary to other diseases. Thus intense 
anemias were found during pregnancy and lactation, in certain gastro- 



PLATE 4 




Pernicious anemia. (Drawing made under the direction of Dr. C. Y. White.) 




° o ° 



5- 



3o 



<2> 



Chlorosis. (Drawing made under the direction of Dr. C. Y. White.) 



DISEASES OF THE BLOOD 



451 



intestinal affections, including atrophy of the gastric and intestinal 
mucosa, ulcerations and carcinoma, and in cases of intestinal parasit- 
ism (uncinaria, bothriocephalus) . A rigid scrutiny of such cases dis- 
closes the fact that these are usually instances of intense secondary 
anemia, though the resemblance to true pernicious anemia may be 
puzzlingly close. In the cases in which true pernicious anemia must be 
admitted the relation may be merely a coincidence. Considerable 
evidence has, however, accumulated to show that gastro-intestinal 
infections and toxemias may be the underlying cause of the disease. 
First, it was shown that pernicious anemia is essentially a hemolytic 
anemia from the facts that the blood-picture is in many respects that 
of direct experimental hemolytic anemias, that the pigmentation of the 
liver and spleen indicate hemolysis, and the urine and feces give evidence 
of excessive liberation of blood-pigment. Second, it was noted that the 
distribution of pigment in the liver and spleen strongly suggested hemol- 
ysis in the area of the portal circulation; and third, the frequent asso- 
ciation of oral infection (glossitis, ulcers in the mouth, on the gums, 
etc.) or gastro-intestinal disease further strengthened this view. The 
discovery of hemolytic substances in the bodies of bothriocephalus taken 
in conjunction with the anemia occasioned by this parasite was another 
factor in the evidence. 

There is some ground for believing that some sort of primary vul- 
nerability of the bone-marrow may be of importance: but it is much 
more probable that the marrow is affected by toxic agents derived from 
outside sources than that there is a primary disease of the marrow. 

Among clinical causes: age (usually after adult years have been 
reached) ; sex (more often females) ; nervous shocks, privation, and 
insanitary surroundings have been noted. Malaria, syphilis, tubercu- 
losis, and other infections, as well as repeated hemorrhages, have been 
regarded as causes. In connection with all of these it must be remem- 
bered that the differentiation of intense secondary anemia from per- 
nicious anemia is often very difficult. 

Pathological Anatomy. — Various secondary changes are met with, 
those in the blood-making organs being most important. The bone 
marrow of the long bones is red and softened and often quite hemor- 
rhagic (for details, see Bone-marrow). This change was formerly re- 
garded as a primary and causal one. At the present time it is looked upon 
as secondary and reactive to a toxemia and, in part, to the hemolytic 
anemia itself. In part, at least, it represents the effort of the bone- 
marrow to compensate for the active blood destruction. The spleen 
is sometimes enlarged, and may be considerably so. (Pigmentation of 
the spleen will be referred to below.) 

The liver, kidneys, and especially the heart suffer degenerative 
changes (fatty) in severe cases. Similar alterations in the blood-vessels 
may cause punctate hemorrhages (especially in the retina), or larger 
hemorrhages in various situations. The lesions of the gastro-intestinal 
tract have been referred to. Some of them are doubtless secondary to 
the anemia; others may be primary. 

Degenerations of the posterior and lateral columns of the spinal 



452 



A TEXT-BOOK OF PATHOLOGY 



cord are frequent. They seem to be due to a toxic agent rather than to 
hemorrhages. 

Pigmentation of the liver, spleen, kidneys, and other organs is a 
significant condition in evidence of the active hemolysis supposed 
to occur in this disease. The pigmentation of the liver is most impor- 
tant, and seems to be characteristic. It occurs in the hepatic cells at the 
periphery of the lobules and in the endothelial cells of the lymphatic 
channels and capillaries in the same situation. The pigment is iron- 
containing, and may be well demonstrated by applying the iron reac- 
tions (sulphid of ammonium; hydrochloric acid and ferrocyanid of 
potassium — forming Prussian blue). 

Decided urobilinuria is an evidence of the active hemolysis, and 
quantitative determinations of urobilin in the feces and urine are used 
as a measure of the degree of hemolysis. 

The Blood. — The color of the blood is often strikingly pale; though 
it may be dark in spite of marked anemia. In some strikingly hemo- 
lytic cases the blood-plasma may be deeply tinged with hemoglobin or 
with bile-pigment. The specific gravity is reduced. The marked feat- 
ures of the disease are pronounced oligocythemia, marked changes in the 
character of the red cells, and a color-index somewhat above normal, 
which contrasts with the low color-index of severe secondary anemias. 
The oligocythemia progresses rapidly, and in ordinary cases the number 
of red corpuscles sinks to 1,000,000 or less per cubic millimeter; at the 
same time changes in size (microcytes and megalocytes) and in shape 
(poikilocytes) make their appearance, and reach grades rarely attained 
in other diseases. An important feature is the number of macrocytes. 
A general survey of the microscopical field at once indicates that the 
average size of the corpuscles is evidently increased. Nucleated red 
corpuscles are always present in some numbers and are usually abundant. 
The megaloblastic and polychromatophilic forms as a rule, predominate; 
but in some cases the normoblastic forms are more abundant. Karyoki- 
netic figures may be found in the nuclei. Polychromatophilia and basic 
granulation are generally pronounced and the proportion of skeined cells 
is definitely increased. The leukocytes may be decreased or normal in 
number; in the terminal stages leukocytosis is not uncommon, and it 
may exceptionally become quite marked. The differential count shows 
a pronounced relative decrease in polymorphonuclear neutrophiles and 
a corresponding increase in lymphocytes. The large mononuclear 
leukocytes are usually more abundant than in health, and myelocytes 
often occur in small numbers. In the terminal leukocytosis of perni- 
cious anemia the lymphocytes predominate. 

APLASTIC ANEMIA 

Occasional cases of severe anemia running a rapid course to a fatal 
termination have been reported, in which the bone-marrow has shown 
a high grade of hypoplasia or even total aplasia. In these cases the 
blood gives evidence (marked reduction in the number of red cells, low 
color-index, great reduction of the proportion of polymorphonuclear 
cells, relative and actual increase of lymphocytes, absence of myelo- 



/ 



DISEASES OF THE BLOOD 453 

cytes and very few nucleated red cells) of the inactivity or aplasia of the 
marrow. 

The cause of tliis condition is entirely obscure. The absence of 
evidences of hemolysis separate it from pernicious anemia but the known 
effect of certain poisons (benzol, etc.) suggests that an unknown agent 
may act primarily upon the bone-marrow. 

The bone-marrow is yellow or white, and on microscopical section 
the specific marrow cells may be wholly wanting. 

HEMOLYTIC ICTERO -ANEMIA 

In recent years several clinical types of hemolytic anemia with 
jaundice have been described. These may properly be discussed here 
because of the close relationship in pathogenesis and the difficulty 
in fully differentiating some of these conditions, either clinically or 
pathologically, from genuine pernicious anemia. The evidences of 
hemolysis are more striking in these diseases, while the indications 
of bone-marrow reaction are less marked, but border-line cases merge 
gradually into the picture of pernicious anemia. 

A congenital and an acquired form of hemolytic ictero-anemia have 
been described. In each there is more or less pronounced anemia, 
jaundice, and splenic enlargement. The congenital form often affects 
several members of a family, is comparatively mild, and may continue 
for years without grave disturbance of health. Splenic enlargement 
is marked. In the acquired form the anemia and jaundice are more 
marked and splenic enlargement usually less so. The prognosis is more 
grave. In both, the evidences of hemolysis (jaundice, without acholic 
stools, urobilinuria, hemorrhagic tendencies) are pronounced. The 
red corpuscles show decided fragility, being hemolyzed in much more 
concentrated salt solutions than are normal red corpuscles. 

LEUKEMIA 

Definition. — Leukemia is a hyperplastic disease of the hemogenic 
organs accompanied by increase in the number of leukocytes in the 
circulating blood, and by the presence also of cell types not found 
normally outside the blood-making tissues. Some of the cell types 
are probably wholly pathological. 

Etiology. — The actual cause of leukemia, as well as the essential 
nature of the disease, remain obscure. Various diseases (malaria, syphilis, 
rickets, etc.) have been regarded as predisposing causes. The same is 
true of pregnancy, lactation, traumatism, exposure, and other in- 
fluences. To some, heredity has seemed to be an important element. 

Infection has been suspected as the direct cause of leukemia by many 
observers, and various forms of bacteria have been discovered in the 
blood and tissues. There are certainly some very striking facts in favor 
of an infectious nature, the most important being the apparent con- 
tagiousness in a few cases and a very similar blood picture (lymphemia) 
in a small number of cases of undoubted infection in which the blood 
returned to the normal after subsidence of the infection. The various 
micro-organisms need not be enumerated, as none of them has been 
proved to be pathogenic. Bodies resembling protozoa have been found 



454 



A TEXT-BOOK OF PATHOLOGY 



in the blood and in the organs (lymphatic glands), but the nature and 
significance of these are uncertain. 

Pathological Anatomy.— It is impossible to classify leukemia with 

certainty, but the evidence at present seems to justify the belief that it 
is closely related to neoplastic processes. 

It is impossible to overlook a certain suggestion of relationship to 
newgrowths. The discovery of mitotic marrow cells in secondary 
deposits or leukemic infiltrations in various organs, the reversionary type 
of the cellular hyperplasia in the marrow, glands and elsewhere on the 
one hand and the occurrence of certain forms of tumors with occasional 
or continued leukemia-like blood picture (leukosarcoma; chloroma, 
myeloma) are certainly strikingly suggestive of such a relationship. 
Reference to this aspect of the matter will be found in the sections on 
Lymphatic Glands, Bone-marrow and Lymphoma. 

In a certain sense the lesions of leukemia might be classed as hyper- 
trophy or hyperplasia of the hemogenic tissues ; but there is evidence of a 
progressive process that goes beyond the limits of ordinary hypertro- 
phies. Enlargement of the spleen or of the lymphatic gland is the 
conspicuous pathological feature. The secondary lesions in organs that 
have ceased to be active hemogenic structures (spleen, liver, and peri- 
vascular tissues elsewhere) appear to be metaplastic, in the sense that 
the endothelia may reassume a latent capacity and as in fetal life initiate 
new series of blood-making cells. This process rather than metastasis or 
mere deposition may account for the foci of myeloid or lymphadenoid 
tissue found in practically all parts of the body. Two types of leukemia 
may be distinguished: the myeloid or myeloic and the lymphatic. The 
former originates in the bone-marrow, and is characterized by hyper- 
plasia of the myelocytic series of cells. Not only myelocytes, but their 
predecessors, myeloblasts and various intermediary stages representing 
undeveloped myelocytes, may make up the bulk of the tissue. The 
erythroblastic cells are crowded out, though not invariably, and exception- 
ally may be conspicuous. In certain cases, especially in very acute 
forms, myeloblasts cells difficult to distinguish from cells of the lympho- 
cytic series may be conspicuous both in the lesions of the bone-marrow and 
other organs and in the blood. Many if not most of the cases of 
so-called acute lymphatic leukemia belong in this group. Lymphatic 
leukemia originates in the lymphatic glands or other lymphadenoid 
tissues, and consists essentially in an active proliferation of lymphocytes. 
The bone-marrow, spleen, and other organs may be secondarily involved. 
The contention that all forms of leukemia originate in the bone-marrow, 
which was at one time commonly believed, was largely based upon the 
discovery that sometimes in so-called acute lymphatic leukemia the 
bone-marrow was found affected and not the lymphatic glands. In 
the light of present knowledge these cases were probably instances of 
myeloblasts leukemia. 

Occasionally the primary disease is in the lymphadenoid tissues of 
the gastro-intestinal tract. Primary dermal leukemia has been de- 
scribed (lymphodermia perniciosa), but is not satisfactorily established. 

Among the secondary lesions of leukemia are invasions of the liver, 
kidneys, lungs, heart, and other tissues. The organs show areas of light 



PLATE s 




Myelogenous leukemia: 1, Neutrophilic myelocytes; 2, eosinophilic myelocyte; 3, 
basophilic myelocyte; 4, 5, 6, leukocytes — neutrophilic, eosinophilic, and basophilic re- 
spectively; 7, large mononuclears of the lymphatic and endotheliocyte type; 8, large 
mononuclears of the promyelocyte type; 9, transitional cells; 10, small mononuclears, 
lymphocytes; 11, nucleated erythrocyte. 




DISEASES OF THE BLOOD 455 

color, or a streaked or mottled appearance, due to masses of myelo- 
cytic or lymphoid cells (Fig. 191). Secondary degenerations of the 
heart, liver, and kidneys may result from the deposits, or from the im- 
poverished state of the blood and the presence of toxic substances. 
Scleroses of the spinal cord may be met with, as in pernicious anemia. 

The blood is often light in color and may be quite milky in appear- 
ance. The specific gravity is lowered. Coagulation is slow; this has 
been attributed to the presence of 
albumoses in the blood. 

The conspicuous feature in the 
blood is the increased number of 
leukocytes. In moderate cases there 
are from 100,000 to 300,000 white cor- 
puscles per cubic millimeter. In severe 
cases the number is much greater; 
while in mild or beginning cases, or in 
cases under active treatment, the num- 
ber may for a time be normal or sub- 
normal. Rapid fluctuations in number 
are very common. 

Leukemia is usually a chronic disease. 
The blood-picture indicates the type 
of the lesions, and we may thus . f 16 - 191— Lymphoid infiltrations 

; i-i iix- between the renal tubules, from a 

recognize a myeloid or lymphatic case G f leukemia, 
form. 

Myeloid Type. — Enlargement of the spleen is the conspicuous clin- 
ical feature. The blood presents a great excess of white corpuscles 
and more or less decided poverty in red cells. The proportion of 
white to red corpuscles is often 1 : 3, 1 : 2, or even 1:1. Large mono- 
nuclear leukocytes (including normal mononuclear and transitional 
elements and myelocytes) predominate over the lymphocytes and 
polymorphonuclear elements (see Plate 5). The latter two forms 
however, are actually increased. Myelocytes are usually found in 
great numbers, and evidence the myeloid nature of the disease. Not 
only the typical neutrophilic myelocyte, but more or less abundant 
eosinophilic and basophilic forms and some without granules or with a 
mixture of basophile and neutrophile granules may be found. Cells 
corresponding to the myeloblasts may also be found, sometimes abun- 
dantly, especially in acute cases. There is usually an actual increase in 
the number of eosinophile elements, but the percentage proportion is 
rarely increased. Basophilic leukocytes (mast-cells) are present in 
numbers greatly in excess of those found in health. Karyokinetic leuko- 
cytes are found in small numbers. The red corpuscles present the usual 
features of anemic blood, and nucleated forms, especially normoblasts, 
may be abundant. The blood-picture is an extremely variegated one, 
and the predominence of large cells is the feature that stands out most 
prominently. 

A peculiar constituent of the blood are the Charcot-Neumann crys- 
tals. These are polyhedral, needle-shaped crystals of uncertain com- 
position, met with in the blood after death or some time after removal 



456 



A TEXT-BOOK OF PATHOLOGY 



from the body, and exceptionally in the fresh blood. They were first 
detected in the bone-marrow. 

Lymphatic Type. — Enlargement of lymphatic glands is the most 
distinctive clinical feature. The leukocytes are usually less abundant 
than in the myeloid type. The lymphocytes predominate very greatly, 
but actual excess of large mononuclear forms and polymorphonuclear 
leukocytes is observed. Contrasted with myeloid leukemia the striking 
feature is the abundance of small cells — lymphocytes. The larger 
lymphoblasts are rarely conspicuous except perhaps in certain acute 
cases. Myelocytes occur in small numbers; exceptionally in consider- 
able proportion. The number of red corpuscles is decreased and nucle- 
ated red cells may be present. 

Acute Leukemia.- — A separate description of acute leukemia is de- 
sirable, because in its clinical manifestations there are striking differences 
from those seen in chronic leukemia and because it is difficult to deter- 
mine whether a given case is myeloid or lymphatic. In the rapid prog- 
ress of the disease cells of great immaturity are cast into the circulation 
and opinions vary as to their nature. Some hold that these are lympho- 
blastic; others, that they are myeloblasts. Upon the whole, the latter 
view seems to be more tenable. 

Acute leukemia seems, in some respects, a distinct type of the dis- 
ease, and the symptoms are strongly suggestive of an infectious condi- 
tion. The duration is usually from a few weeks to a few months after 
the first symptoms are noted. Gastro-intestinal lesions (ulcers in the 
mouth, stomach, and intestines) and hemorrhagic manifestations (pur- 
pura) are frequent. Moderate enlargement of the lymphatic tissues 
and infiltrations of the organs are discovered, and parenchymatous 
changes in the organs are constantly present. 

The blood shows a varied picture. The total number of leukocytes 
may vary from a very moderate increase above the normal to several 
hundred thousand per cubic millimeter. Mononuclear elements are 
conspicuous, the predominating cell being one that resembles lympho- 
cytes or lymphoblasts, and also the smaller myeloblasts. The nuclei 
are large, round, or horseshoe shaped, and stain faintly; the protoplasm 
forms a somewhat narrow rim around the nucleus. The polymorpho- 
nuclear cells and eosinophiles may be actually, but not relatively, in- 
creased in number; myelocytes are occasionally present. Considerable 
reduction in the number of red corpuscles is a usual feature of acute 
leukemia. Nucleated red corpuscles (especially normoblasts) are gener- 
ally present. 

Aleukemic Leukemia. — Cases have been described in which enlarge- 
ments of the lymphatic glands or spleen have for a time been unaccom- 
panied by increased numbers of leukocytes in the blood and later have 
shown definite pictures of leukemia. In some instances histological 
studies of the lesions have shown definite characteristics of lymphatic 
or much less frequently myeloid leukemia. On the other hand in some 
cases of pronounced leukemia the blood has, spontaneously or under 
treatment, lost all the characteristics of the disease. To this extent 
there can be no doubt of the occurrence of aleukemic leukemia, but the 
tendency has manifested itself in some quarters to extend the term un- 



PLATE 6 




Chronic lymphatic leukemia. (Drawing made under the direction of Dr. C. Y. White.) 



DISEASES OF THE BLOOD 



457 



duly so as to include conditions probably not leukemic and to exaggerate 
the frequency of such cases. 

HODGKIN'S DISEASE 

This disease presents a certain superficial resemblance to leukemia 
in the enlargement of the lymphatic glands and sometimes of the spleen, 
and to a less extent in the histology of the lesions. As the differentiation 
has become more definite the old term pseudoleukemia has been generally 
abandoned. 

The original description of Hodgkin was mainly clinical and referred 
to a condition characterized by pronounced enlargements of certain 
groups of lymphatic glands. Later the name pseudoleukemia was used 
for this group of cases on the assumption that the histology of the glands 
is identical with that of leukemia but the blood picture is not leukemic. 
It is admitted at the present time that there is a group corresponding to 
the clinical description of Hodgkin but without the histology of leukemic 
glands, but certain European authors still use the term pseudoleukemia 
in the belief that there is another group of cases characterized by leu- 
kemic histology of the glands without the blood picture of leukemia. 
Others would designate this as aleukemic leukemia. 

The glandular features and pathology will be described under Lym- 
phatic Glands. 

The blood picture in Hodgkin's disease is variable. There is always 
more or less reduction in the number of red corpuscles and the propor- 
tion of coloring matter and sometimes the anemia is very pronounced. 
The leukocytes are usually moderately increased in number and occa- 
sionally quite decided leukocytosis occurs. In certain cases particularly 
where the total count is only moderate the lymphocytes and large mono- 
nuclear elements are conspicuously increased in relative number; in other 
instances marked polymorphonuclear neutrophile leukocytosis is met 
with. Some have attempted to define stages in the blood picture but 
this seems of doubtful expediency. In a minority of cases there is dis- 
tinct eosinophilia. Blood platelets are increased in number. 

Pseudoleukemia Infantum 

Under this name von Jaksch described a form of leukocytosis, with 
enlargement of the spleen and liver, occurring in children. There is rapid 
and excessive oligocythemia, and the leukocytosis is pronounced. Leu- 
kocytes of all types are present, and give to the blood a curiously varie- 
gated appearance. There is no striking difference, however, from the 
characters of the blood met with in other cases of leukocytosis in infancy. 
Rickets and congenital syphilis seem to be closely related to this form 
of disease. 

The enlargement of the spleen and liver is not of the nature of that 
seen in leukemia, but is simply a chronic hyperplastic condition. 

FOREIGN BODIES AND PARASITES 

Foreign Bodies in Blood. — Various kinds of particles may gain 
access to the blood-current and may be carried to peripheral parts of 
the circulation. In anthracosis a lymphatic gland may attach itself and 



458 



A TEXT-BOOK OF PATHOLOGY 



after softening, rupture into a vein. The particles of carbon are thus 
distributed in the blood. Small portions of tumors, of the heart-valves, 
calcareous particles from atheromatous plates, and portions of thrombi 
are frequently transported by the blood. Charcot crystals are met with 
in leukemia, and pigment-matter, due to disintegration of the blood 
itself, is seen in malaria. 

Parasites in the Blood. — Among the animal parasites are the mala- 
rial Plasmodium, which occurs within the red corpuscles or free in the 
plasma; the Schistosomum hcematobium, which occupies the portal vein ; 
the embryos of the Filaria bancrofti, and the trypanosomes. (These are 
more fully described in the section on Parasites.) Portions of hydatid 
cysts or of cysticerci and trichinae are occasionally conveyed in the 
circulation. 

Vegetable Parasites. — Mould-fungi sometimes gain entrance into the 
circulation and lead to serious embolism, as does also the Streptothrix 
actinomyces. Of the pathogenic bacteria, the spirochete of relapsing fever 
and the bacillus of anthrax are most abundant in the blood. Other 
micro-organisms are more difficult of demonstration, though many kinds 
of micro-organisms have been demonstrated morphologically and in 
culture. 



CHAPTER II 



DISEASES OF THE LYMPHATIC TISSUES 
The Spleen 

Anatomical Considerations. — The spleen is practically a com- 
' plicated lymphatic gland with close relations to the circulation. It 
is enclosed in a fibrous capsule, from which trabecule enter into the 
substance of the organ and give off subdivisions that unite and form a 
framework, in the meshes of which lymphoid tissue is embedded. The 
splenic artery enters at the hilum and subdivides into numerous branches 
which traverse the trabecule. Side branches are given off from the 
trabecular arterioles ; these penetrate the splenic pulp and are surrounded 
by denser aggregations of lymph-cells, which are visible to the naked eye 
as the Malpighian bodies. All of the terminal arteries discharge their 
blood directly into the spaces of the splenic pulp, from which it is re- 
collected into the veins. The spaces contain, in addition to lymphoid 
cells and red blood-corpuscles, larger cells, endothelial in type, often 
containing pigment granules or even blood-corpuscles. 

The weight of the spleen in the adult varies from 140 to 200 gm. 

The splenic function remains in doubt. It seems to have some con- 
nection with the process of manufacture of leukocytes, and is one of the 
sources of red blood-corpuscles in early life. Because of the anemia 
following splenectomy, with hyperplasia of bone marrow, certain 
observers have ascribed to the organ a hematopoietic function during 
adult life. Whether or not this be true, it seems that it is surely one 
of the principal places of normal destruction of worn out red corpuscles, 
and in cases of general hemolysis, or blood-destruction, the blood- 
pigment and fragmented corpuscles are especially arrested in this organ. 
It has something to do with the iron chemistry of the body. The 
muscular tissue of the capsule contracts and expands, assisting thus in 
the propulsion of blood and lymph. 

Pathological Physiology. — The relations of diseases of the spleen 
to the general health are still obscure. It has been held by some pathol- 
ogists that this organ plays an important part in the process of im- 
munization or combating infectious diseases. The fact that bacteria 
and foreign bodies circulating in the blood are arrested to a large extent 
in the spleen warrants the suspicion that this organ is important in dis- 
posing of irritants, and thus preventing their gaining access to more 
vital parts. Experimenters, however, have found no uniform increase 
of susceptibility to micro-organismal inoculation on the part of splenec- 
tomized animals. For the present, therefore, we can only suspect that 
removal or disease of the spleen renders individuals more vulnerable to 
infections. 

459 



460 



A TEXT-BOOK OF PATHOLOGY 



The effect of removal of the spleen in human beings is surprisingly 
slight. A certain amount of anemia and general deterioration of health 
follow the operation, but seem to be the result of the operation per se, 
rather than of removal of the organ. Subsequently, complete health 
is regained. Some compensatory (?) enlargement of the lymphatic 
glands has been observed after splenectomy. This organ shows con- 
siderable alterations in size, appearance and histology during acute 
infectious diseases, notably typhoid fever, a fact that strengthens the 
assumption in some quarters that it is active in a protective manner. 
The pathologist is accustomed to look first at the spleen for evidences 
of exaggerated blood destruction, found in the form of increased large 
mononuclear cells carrying pigment and of irregularly placed free pig- 
ment. 

Excessive enlargements of the spleen lead to a rotation downward 
of its anterior extremity and the exposure, from beneath ribs, of a palpable 
edge, sometimes notched. This condition may occur in typhoid, malaria, 
primary splenomegaly and the like. 

ABNORMAL DEVELOPMENT AND SITUATION 

Complete absence of the spleen has sometimes been noted in children 
that lived for several years. More commonly slighter defects, such as 
unusual smallness or excessive lobulation, occur. Very often small 
accessory spleens, the size of a pea or a marble, are found, occuring 
chiefly in the abdominal cavity, but also found elsewhere. 

Movable Spleen. — The organ may be quite movable, either as a 
congenital condition or as the result of enlargement and resulting traction 
upon its attachments. Downward displacement and movability are 
frequently found in cases of splanchnoptosis. Twisting of the pedicle 
of a movable spleen may lead to strangulation of the circulation and 
consequent necrosis. 

CIRCULATORY DISTURBANCES 

Anemia may occur in cases of general anemia resulting from hemor- 
rhage or inanition. The spleen presents a contracted appearance, the 
capsule being wrinkled, and on section the substance is found to be 
lighter in color and the fibrous stroma is more prominent than normal. 

Hyperemia may be active or passive. Active hyperemia is a physio- 
logic condition during digestion, when the spleen increases somewhat in 
size. Intense congestion occurs in a number of diseases, but so com- 
monly passes into inflammation that it will be described under that 
heading. Passive congestion is most marked in cases of cirrhosis of the 
liver, but also occurs in association with hyperemia of other organs as 
the result of cardiac failure, of emphysema, or of other diseases obstruct- 
ing the larger venous channels. The spleen is greatly enlarged and of a 
dark-red color, and the capsule is often tensely distended; the Mal- 
pighian bodies are less distinct than normally. After long continuation 
of the process hyperplasia of the trabecule and the fibrous stroma 
generally takes place. The spleen may be greatly enlarged and very 
dense at this stage. Subsequently contraction of the newly formed 
fibrous tissue may lead to atrophy of the proper splenic substance and 



DISEASES OF THE LYMPHATIC TISSUES 



461 



increased induration of the organ {cyanotic induration). Considerable 
pigmentation is found in such cases from the destruction of the stag- 
nated blood (see p. 465). H. A. Christian, in a study of the spleen in 
cases of chronic passive congestion and cirrhosis of the liver, found no 
change of any kind in the Malpighian bodies of the spleen. The pulp 
was relatively poor in cells and the blood sinuses generally dilated. 
There was also, as a rule, a definite layer of low cuboidal endothelial 
cells lining the sinuses. In a majority of the cases there was increase 
of the connective-tissue framework. In the 10 cases with no increase 
in connective tissue, the spleen felt almost equally firm, showing that 
the firmness was due to vascular distention. The same factor probably 
enters into the production of firmness in all of the cases. Proliferation 
of the reticular tissue of the pulp with little or no change in the white 
fibrous and elastic tissue of the organ, constituted the main connective 
tissue change. An increase of connective tissue around the small 
splenic arteries and within the Malpighian bodies was sometimes seen. 

Hemorrhages in the spleen may be the result of traumatism, when 
large hematomata may form, especially just beneath the capsule, some- 
times to the extent that rupture occurs leading to a fatal hemorrhage 
into the peritoneum. The escape of a large quantity of blood also 
occurs in traumatic rupture of the organ from falls and blows. Small 
areas of hemorrhage are not infrequent in intense infections with splenitis, 
but it is difficult to draw a line between hemorrhage and the overfilling 
of the spaces by congestion, since the blood under normal conditions 
enters directly into the splenic pulp. 

Embolism of the splenic artery is very common in cases of endo- 
carditis or thrombosis in the left heart or aorta. As the spleen contains 
abundant " terminal arteries," infarction is the common result. The 
area may remain light colored, constituting an anemic infarct; or it 
may become overfilled with blood, when hemorrhagic infarction results. 
In either case there is a wedge-shaped lesion, with the base toward the 
surface of the organ and the apex within, harder than the surrounding 
tissue and usually somewhat elevated. The swelling and elevation 
in the case of anemic infarction are partly due to a zone of hyperemia 
which usually surrounds it. Complete resolution may occur, but more 
commonly the area involved undergoes coagulation necrosis and soften- 
ing, and as absorption takes place fibrous overgrowth gives rise to the 
formation of a scar. There may be numerous infarcts of small size or a 
single large one sometimes occupying as much as half of the organ. 
(Septic infarction and its results are discussed under Abscess of the 
Spleen.) 

Thrombosis of the splenic vein may occur in association with throm^ 
bosis of the portal vein. It causes intense passive hyperemia of the 
spleen. Occasionally calcification of thrombi gives rise to the forma- 
tion of splenic stones. 

INFLAMMATION OF THE SPLEEN, OR SPLENITIS 

Splenitis occurs in a variety of conditions, and may present itself 
in several forms, among which the acute enlargement of the spleen of 



462 



A TEXT-BOOK OF PATHOLOGY 



infectious diseases and localized splenitis, or abscess of the spleen, 
are the principal. 

Diffuse Splenitis. — The splenic enlargement of infection occurs 
particularly in typhoid fever, malaria, septicemia, typhus, and relapsing 
fevers; and less markedly in pneumonia, scarlet fever, small-pox, and 
influenza. In the earlier stage the spleen is simply congested and pre- 
sents a dark-red color; is firm, and the capsule more or less distended. 
On section, the Malpighian bodies are usually obscured, and there may 
be visible areas of hemorrhagic extravasation. Microscopically at this 
stage the blood-vessels are all found overdistended, and the spaces 
within the splenic pulp are filled with red and white blood-corpuscles. 
If the process has continued for some time, pigment masses and de- 
generated corpuscles are visible, but there are as yet no evidences of 
inflammatory hyperplasia of the splenic pulp or stroma. 

As the process advances the spleen may become softer and may 
be quite diffluent^ On section, the substance is now found to be deep 
red or red-gray, the Malpighian bodies indistinct except in violent septic 
cases, when they are decidedly prominent, presenting themselves as 
yellowish-gray punctse, somewhat resembling miliary tubercles. The 
capsule of the oggan may still be tensely distended, but in other cases is 
wrinkled, as if some shrinkage of the spleen had occurred in the change 
from the first stage of congestion to that of . well-defined inflammation. 

There are two illy defined groups into which these acutely enlarged 
spleens can be divided, the characters of which correspond fairly well 
with the histological findings. Those which remain from the start as 
firm gray-red organs, seen in pneumonia and septicemia, have a pulp 
composed almost exclusively of small mononuclear cells, with a moderate 
representation of polynuclears and other myeloid cells; some have 
ascribed these latter cells to an attempt to supply leucocytes by hyper- 
plasia of the assumed myeloid tissue in the spleen. The type of en- 
largement which remains deep red, soft, even succulent, as seen in 
typhoid fever, shows histologically an enormous increase of the large 
mononuclears, derived from sinus and vascular endothelium, containing 
red blood cells and debris. The follicles in the first type show hyperplasia 
with tightly packed structure or perhaps with an increase of the central 
perivascular large mononuclears while in the second group the follicles 
are about normal. Areas of necrosis may be found occasionally in 
both types but more often in the second. 

In still later stages signs of degeneration may become prominent. 
This is apparent in the increasing softening of the organ, while under 
the microscope there are found cellular degenerations leading to the 
formation of detritus, to fragmentation of the nuclei of the cells, and to 
pigmentation by disintegration of red blood-corpuscles. 

Terminations. — Most frequently complete resolution occurs. Some- 
times, however, persistence of the inflammation is noted; and, when 
repeated attacks of the infection occasion repeated attacks of splenitis, 
chronic inflammatory hyperplasia is the result. This is especially 
marked in the "ague-cake" spleen of malaria. Spontaneous rupture 
or rupture from slight trauma may result from the softened and dis- 
tended condition of the organ. Finally, suppuration may ensue, either 



DISEASES OF THE LYMPHATIC TISSUES 



463 



in the form of a diffuse softening and purulent infiltration of the entire 
organ, or in the form of a localized abscess beginning at the point of 
greatest involvement. 

Circumscribed Splenitis, or Abscess of the Spleen. — This may 
be the termination of an. acute diffuse splenitis, particularly in septi- 
cemia and typhoid fever; or it may be caused by extension of diseases 
of neighboring structures, by septic embolism, or traumatic injuries. In 
the last case, the mechanical injury of the spleen merely furnishes suitable 
conditions for the action of bacteria conveyed to it through the cir- 
culation, or the spleen is actually penetrated and infected. Occa- 
sionally abscess may result from the perforation of gastric ulcers or from 
the extension of other inflammations 
in the vicinity. An important group 
of cases is that in which the abscesses 
are embolic and metastatic (Fig. 192). 
Such cases are met with in malignant 
endocarditis or thrombosis of the 
heart or aorta, and in cases of pyemia 
following other infective conditions. 
The first effect of the embolism is a 
hemorrhagic or anemic infarction, but 
this soon undergoes suppurative soft- 
ening beginning at the apex of the 
infarct. Metastatic abscesses are most 
common near the surface of the organ 
and are usually multiple, though a 
single cavity occupying the greater 
part of the organ may occur. Small 
collections may become absorbed or 
inspissated, leaving a necrotic or 
cheesy collection as a residue. Larger 
collections may be discharged by per- 
foration into the stomach or intestines, 
or they may break into the peritoneal 
or pleural cavity, causing septic 
peritonitis or pleuritis. 

Chronic Inflammation or Chronic Hyperplasia of the Spleen. — 
Attention has already been called to the slow hyperplasia of the con- 
nective tissue and sometimes of the splenic pulp occurring in conse- 
quence of chronic passive congestion and of repeated attacks of acute 
splenitis. The spleen is large in size and firm. The capsule is often 
tensely distended and may be greatly thickened. The thickening is 
either diffuse or circumscribed, patches of almost cartilaginous hardness 
occurring in the latter case. Attachments by fibrous adhesions may fix 
the spleen to the diaphragm or the neighboring organs. On section the 
spleen is found dark in color from the presence of abundant pigment, and 
the excess of fibrous tissue may be visible to the naked eye. Micro- 
scopically, increased thickness of the fibrous trabeculse, hyperplasia 
of the connective tissue about and within the follicles and that of the 




Fig. 192. — Embolic abscess of the 
spleen (from a specimen in the Museum 
of the Philadelphia Hospital). 



464 



A TEXT-BOOK OF PATHOLOGY 



walls of the small blood-vessels, and pigmentation with altered blood 
pigments are the conspicuous features. 

A somewhat different form of chronic hyperplasia is dependent 
upon syphilis, especially upon the congenital form. In this the appear- 
ances are much the same as in the cases following splenitis or conges- 
tion, but, as a rule, the color is somewhat lighter from the fact that the 
process is a slowly hyperplastic one without acute inflammatory or con- 
gestive manifestations. Somewhat similar appearances result from 
rickets. The indurative processes in the spleen following cirrhosis of 
the liver may be due at times to thrombosis of the liver veins, but this 
does not always exist. It has been suggested that circulating toxins are 
responsible. The enlarged organ of malaria, "ague coke," is of a bluish 
black color due to a great amount of pigment, to the accumulation of 
which the chronic fibrous overgrowth is in all probability due. 

Splenic Anemia ; Splenomegaly. — These terms have been used to 
describe a clinical condition distinguished by chronic enlargement of the 
spleen due mainly to fibrosis beginning in the follicles, gastro-intestinal 
disturbances, a tendency to hemorrhages from the stomach, and later 
by progressive weakness and ascites. Anemia of chlorotic type may 
occur, especially in the hemorrhagic cases, which seems in some way 
connected with the splenic condition for removal of the organ some- 
times causes the condition. The development of ascites is due to 
secondary cirrhosis of the liver. Cases presenting this association are 
designated Banti's disease. Anatomically the principal lesion is found 
in a really enormous spleen, sometimes weighing five pounds, of purple 
color due to blood stagnated in large venous channels. Where this blood 
is removed what remains is of a dull gray reel color composed of fibrous 
tissues and remnants of pulp and follicles. The veins supplying the 
organ are much dilated and may be brittle by sclerosis. 

The so-called primary or idiopathic splenomegaly of Gaucher is an 
enlargement of the spleen due to accumulations of endothelial cells 
without much cirrhotic change, associated with enlargement of the 
liver, and pigmentations of the skin, or hemorrhages. The liver and 
lymph-glands may show the endothelial changes as in the spleen. The 
anemia is moderate but irritation of the bone marrow, describable also 
microscopically, may be seen in nucleated erythrocytes and myelocytes 
in the circulating blood. The disease tends to run in families. 

The etiology and nature of these cases is probably varied. At 
autopsy some show merely chronic congestion of the spleen, others a 
more definite chronic hyperplasia; a few have been found to present 
a peculiar proliferation of the endothelium of the sinuses (see Tumors). 

ATROPHY AND DEGENERATIONS 

Atrophy of the spleen is very common in old age. The capsule 
is usually wrinkled and somewhat thickened, and on section the organ 
is more fibrous in appearance on account of atrophy of the splenic pulp 
and proliferation of the stroma. Thickening of the capsule some- 
times appears in the form of white plates of cartilaginous hardness, 
which result from inflammatory overgrowth of the capsule (perisplenitis 
cartilaginea) . 



DISEASES 6F THE LYMPHATIC TISSUES 



465 



Amyloid infiltration occurs more frequently in the spleen than in 
any other organ. The causes are those which lead to amyloid disease 
elsewhere. In most cases the degeneration begins in the Malpighian 
bodies, affecting the walls of the blood-vessels and the lymphoid elements. 
On section in such a case there are seen small round areas about the size 
of a currant-seed, of gelatinous, translucent appearance. These have 
been likened to grains of boiled sago, and the term sago spleen is not 
inappropriate. In other cases a more uniform involvement of the whole 
organ is noted, and the section presents the appearance of boiled ham 
or dried beef (bacony spleen) . Considerable enlargement of the organ is 
noted in such instances, and the tissue is much harder than normal. 
Beginning amyloid degeneration may be difficult to determine micro- 
scopically, but is readily demonstrated by the microscopical staining 
reactions. (See Amyloid Degeneration.) 

Hyaline degeneration has been observed in association with amy- 
loid and independent of the latter. It affects the small blood-vessels and 
the reticulum more particularly. 

Pigmentation is a very common result of chronic congestion as well 
as of repeated acute splenitis; the spleen in cases of cirrhosis of the liver 
and in chronic malaria is, therefore, habitually pigmented. The deposit 
occurs first in the walls of the blood-vessels and later throughout the 
splenic structure, either within the cells or lying free in the tissue. Occa- 
sionally pigment particles derived from the external world are deposited 
in the spleen. This is especially true of dust particles which have reached 
the circulation from softened bronchial glands. In cases of diseases 
of other kinds leading to discharge of foreign bodies or tissue elements 
into the circulation, the arrest not rarely occurs in the spleen, and re- 
active congestion or inflammation with enlargement of the spleen may 
result (spodogenous splenitis). Pigmentation of the spleen is seen in 
progressive pernicious anemia and other conditions in which hemolysis 
occurs. The pigments resulting from the destruction of red corpuscles 
are deposited in the liver, spleen, and other organs. Biliary pigmenta- 
tion of the spleen occurs in various forms of jaundice. Pigment is 
removed or at least ingested by endothelium, lying along trabecule 
and sinuses. Hematoidin is found in infarcts. 

Calcification occurs in the thickened capsule of chronic splenitis 
and in old infarcts, tuberculous or syphilitic areas, and occasionally in 
thrombi of the splenic vein. Parasitic cysts may be surrounded by 
calcification. 

LEUKEMIA AND HODGKIN'S DISEASE 

The spleen is usually involved in leukemia and occasionally in Hodg- 
kin's disease. The former condition is primarily an affection of the 
bone-marrow (myeloid type) or of the lymphatic glands (lymphatic 
type). In either case, however, the spleen is usually involved. In the 
earlier stages the organ is enlarged and soft, and on section exhibits 
evidences of intense congestion. Later, the characteristic hyperplasia 
of myeloid or lymphatic elements causes a lighter color or areas of lighter 
color between the more congested portions. Infarctions, sometimes of 
considerable size, and hemorrhagic or anemic and necrotic, may add to 

30 ' 



466 



A TEXT-BOOK OF PATHOLOGY 



the variegated appearance of the surface of section. Histologicaly in 
myeloid cases there are found areas of myelocytic or myeloblastic hyper- 
plasia, sometimes with giant cells and erythroblasts, characteristic of 
myeloid structure. In lymphatic cases abundant lymphocytes replace 
the normal splenic tissue. 

In Hodgkin's disease the characteristic histological features are to 
be found in two forms, nodular and diffuse. In the former discrete, 
sharply outlined, pale pink or yellow areas, lie between fairly normal 
splenic tissue, and are made up of large pale cells, small mononuclears, 
and a few eosinophiles, about all which fibrotic changes are prominent. 
In the diffuse form the process is more cellular, the large cells being 
numerous but fibrosis is much less marked; in two cases we have seen 
eosinophiles were very numerous. 

TUMORS AND PARASITES 

Sarcoma and Carcinoma.— Primary sarcoma of the round-celled 

or fibrosarcomatous variety has been observed. Secondary sarcoma, 
particularly melanotic sarcoma, is more common than the primary 
growth, and secondary carcinoma occurs. 

Endothelioma.- — A few of the cases of the clinical syndrome called 
splenic anemia have presented a remarkable proliferation of the endo- 
thelium of the splenic sinuses, and authors have variously regarded the 
process as an endothelial hyperplasia or as endothelioma. In a case 
reported by Stengel the process strongly suggested a tumor. 

Cysts are occasionally discovered. They are small and are prob- 
ably due to dilatation of the lymphatic spaces; or to atrophy and cystic 
degeneration of the Malpighian follicles. 

Others are said to be due to an intracapsular injury and hemorrhage, 
with absorption of the solid parts and subsequent encapsulation. Lam- 
ina of clot may be found on the walls. Some authors believe that cysts 
may be due to an invagination of peritoneum. 

Fibroma, angioma, and lymphangioma are very rare. 

Parasites.' — Linguatula rhinaria, echinococcus cysts, and cysticerci 
have been observed. 

INFECTIOUS DISEASES 

Tuberculosis of the spleen may occur in the form of minute miliary 
tubercles, which have a grayish translucent appearance, and are usually 
present in large numbers, especially near and under the capsule where 
they escape detection unless searched for closely in oblique light. They 
may be distinguished from enlarged Malpighian bodies by their greater 
opacity and their grayish rather than yellowish color. Tuberculosis 
also occurs in the form of larger caseous nodules, especially in children. 
In these cases there are seen nodular masses the size of a pea or cherry 
studding the surface and deeper structure of the spleen. This form is 
called Affentuberculose by the Germans, from the resemblance of the 
large nodules to tubercles met with in monkeys. Histological examina- 
tion proves the nodules to be composed of aggregations of tubercles 
undergoing caseation. Very early miliary forms may be without the 
usual caseation and giant cells, consisting merely of collections of epithe- 



DISEASES OF THE LYMPHATIC TISSUES 



467 



lioid cells with a little stroma. It is well to look up these collections 
with suspicion and stain for the bacilli. Klotz's observations indicate 
that miliary lesions occur in this organ more frequently than was formerly 
suspected but that they usually appear at autopsy as healed lesions. 
Primary tuberculosis of the spleen has never been observed. 

Syphilis may present itself in the form of syphilitic gummata, which 
are usually multiple and may be either small or large. They are dis- 
tinguished by their central degeneration or by the fibrous tissue striations 
at the exterior. 

Diffuse hyperplasia of the spleen is a frequent or almost constant 
lesion of congenital syphilis. 

The spleen is the seat of secondary deposits in actinomycosis, glan- 
ders, and leprosy, the lesions following the type characteristic for these 
diseases. 

Perisplenitis. — The capsule of the spleen may be inflamed as a part 
of acute splenitis or from a peritonitis. It is usually of a fibrinous char- 
acter and may resolve or continue into a chronic stage, in which case it 
may have adhesions to adjacent organs or extension into the trabecular, 
or both. The capsule becomes much thickened, gray and opaque. 

The Lymphatic Glands 

Anatomical Considerations. — The lymphatic glands or nodes are 
accumulations of lymphadenoid tissue enclosed in a fibrous capsule, 
into which a number of small afferent lymphatic vessels enter, and 
from which a somewhat smaller number of larger efferent lymphatic 
vessels emerge. The nodes are composed at the periphery of spherical 
lymphatic follicles made up of lymphadenoid tissue, and at the center of 
medullary cords of the same structure. Under the outer capsule and 
alongside of the fibrous trabecular which dip down between the follicles 
and cords are spaces lined with endothelial cells, the lymph-sinuses. 
Through this system of channels the lymph conveyed by the afferent 
vessels filters to the hilum of the glands, where the efferent vessels 
take their origin. Histologically, the lymph-follicles present at their 
centers collections of somewhat large and pale-staining cells with numer- 
ous mitotic figures. These are the germ centers composed of lymph o- 
blasts. Surrounding these are smaller and more deeply staining cells- 
lymphocytes. 

Functions of the Lymphatic Glands. — Two important functions 
of the glands are recognized: a filtering action and blood-cell formation. 
The filtering action of the glands is readily explained by the anatomical 
features described, and is exhibited by the accumulation of bacteria or 
pigment in the lymphatic glands adjacent to an infective lesion or a 
source of pigmentary deposit. What part the regional lymphatic glands 
may play in the local inhibition of infective processes by destroying 
micro-organisms arrested by them is a matter of theory rather than 
present knowledge. 

The blood-cell formation of the lymphatic glands is concerned with 
the production only of lymphocytes and the plasma-cells. Both of 
these cell forms are apparently derivatives remotely of the lining of the 
lymphatic vessels or sinuses and of the germinal centres, and more im- 



468 



A TEXT-BOOK OF PATHOLOGY 



mediately of lymphoblasts. The lymphocytes are relatively small ceils 
with deeply staining nuclei, a marked nuclear membrane, and a some- 
what granular basophilic protoplasm. These are derived from lympho- 
blastic cells (such as are seen in the germ centers of the follicles) — larger 
cell forms with paler nucleus and protoplasm. From these forms under 
pathological conditions may be derived plasma-cells, which are mainly 
distinguished by the eccentric position of the nucleus and the deeply 
staining (basophilic) protoplasm. These cells are especially abundant 
in the round-cell infiltration of inflammation. 

Hemolymph Glands. — Certain of the lymphatic glands of the retroperitoneal 
region differ from ordinary lymphatic glands in having blood-sinuses intsead of lymph- 
sinuses. These have been termed "hemolymph glands." Such glands are less 
frequently found in other situations, such as in the mediastinum, thymus region, 
cervical region, etc. They are usually embedded in fat tissue, and, as a rule, are near 
the wall of some large vessel. The number and size of the blood-vessels connected 
with these glands are remarkable, showing the relation to the hemic circulation. 
Transitional conditions between the typical lymphatic gland and the hemolymph 
gland are met with. Some of the glands resemble splenic tissue, and others the 
marrow tissue. Warthin suggests the terms " splenolymph" and "marrow-lymph 
gland." Pathologically these glands have been found congested or showing evidences 
of increased pigment formation in various types of anemia. They appear to have 
an active hemogenic function in such conditions. 

ATROPHY 

This condition of the lymph-glands occurs in old age and in various 
marasmic conditions. The glands suffer considerable diminution in 
size, the cellular elements being particularly affected; they are, therefore, 
hard, dry, and often irregular in shape. Fatty infiltration may occur 
simultaneously with atrophy, the gland in such cases preserving its size 
and having a decidedly fatty appearance. 

HYPERTROPHY 

This is so closely allied to the conditions designated by the name of 
" lymphoma" that it is difficult to separate the cases which might be con- 
sidered as strictly hypertrophy. In cases of experimental or surgical 
splenectomy, hypertrophy of the lymphatic glands has been observed. 
Chronic enlargement of the tonsils and generalized lymphatic enlarge- 
ment in status lymphaticus may also be considered as forms of hyper- 
trophy. 

STATUS LYMPHATICUS 

This condition is one in which there is a marked preservation after 
early infancy or childhood of the relative excess of lymphatic tissue that 
characterizes the earlier years of life. A pronounced feature of the 
anatomy of childhood is the richness in lymphatic tissue and the high 
percentage of lymphocytes in the blood. After the first few years, but 
especially after puberty, this excess of lymphadenoid structures disap- 
pears, but in certain individuals it persists, leading, it is believed, to sud- 
den deaths after administration of ether or following rather trifling 
injuries. In such cases the term "status lymphaticus" is applied. 
Formerly this condition was regarded as closely identified with^status 



DISEASES OF THE LYMPHATIC TISSUES 



469 



thymicus, in which persistence of the thymus gland after the time of its 
normal atrophy is met with. Certain recent authors separate the two 
conditions, and certainly status lymphaticus is much more frequently 
unaccompanied by persistent thymus than accompanied by it. Three 
deaths from status lymphaticus were seen by one of us during the late 
war, in only one of which was the thymus discovered and then it was 
insufficient to have caused any compression. * 

Among the physical features of the lymphatic status are hypertro- 
phies of the lymphadenoid tissues of the pharynx, the back of the tongue, 
the nasal passages, enlarged tonsils, cervical lymphatic glands, Peyer's 
patches, etc. There is a tendency for the lymphatic tissue to leave the 
ordinary confines of its capsule and grow diffusely. The blood-vessels 
are usually hypoplastic and the heart may be in the same condition. 
Enlargement of the spleen and a persistent thymus may be found. The 
blood presents the infantile excess of mononuclear elements (mono- 
nucleosis), especially lymphocytes; in some cases the bone-marrow 
remains persistently infantile (red) in type. These anatomical pe- 
culiarities are seen in individuals whose development is usually other- 
wise incomplete for in males feminine characters may be seen while in 
females the urogenital tract is hypoplastic and the face may be hairy. 
In recent years particular attention has been called to a lack in develop- 
ment of the chromaffin system. The adrenals are deficient and the 
other structures containing chromaffin elements are more or less defec- 
tive. To this lack of chromaffin substance, and the consequent de- 
ficiency of its secretions (adrenalin, etc.), may be due the low tension 
of circulation, and perhaps sudden death, which sometimes occurs. 

Certain writers describe as a separate form from the type above 
discussed, and which they regard as primary status lymphaticus, a second- 
ary form which is developed in childhood or, later, in persons who had 
previously shown no abnormal structural conditions. Such secondary 
forms are said to occur as a result of rickets, syphilis, tuberculosis, and 
other infections, asthma and various diseases of the glands of internal 
secretion, such as Addison's disease, Graves' disease, myxedema, etc. 
The physical peculiarities are the same, but less pronounced than in the 
primary form. Rather too much weight seems to us to have been given 
to the blood condition (mononucleosis ; lymphocytosis) in suggesting the 
existence of a status lymphaticus in some of these diseases. 

DEGENERATIONS 

Fatty infiltration is sometimes seen in cases of general obesity 
and also, as before mentioned, in atrophy of the glands. 

Amyloid infiltration is met with in cases of general amyloid dis- 
ease, and particularly in the cases in which the intestines are affected. 
The lymphatic glands may, however, be independently involved in 
cases of tuberculosis attended with suppuration. In such instances the 
adjacent lymphatic glands are most likely to suffer amyloid change. 
The morbid process rarely leads to marked alteration of the glands, but 
the amyloid material may be demonstrated by the staining reactions 
peculiar to it. The connective tissue of the trabecule and around the 
blood-vessels is first affected; later, the endothelial cells. 



470 



A TEXT-BOOK OF PATHOLOGY 



Hyaline degeneration has been observed. It affects the blood- 
vessels and connective tissue of the glands. 

Calcification not infrequently forms the terminal condition in 
cases of necrosis or induration of the glands in consequence of tuber- 
culous or simple inflammation. There may be small calcareous granules 
scattered through the gland, or the entire gland may be infiltrated. 

Necrosis may occur in consequence of tuberculous or syphilitic 
affections, or of simple inflammation. In the former cases, particularly 
in tuberculosis, the center of the gland or the entire gland becomes 
cheesy and soft, often liquefying and discharging the contents by rupture 
of the capsule. In consequence of simple inflammation, as in certain 
infectious fevers (typhoid, diphtheria, scarlet fever), a different form of 
necrosis is met with, areas of the gland becoming soft, pultaceous, and 
sometimes putrid. The gland may rupture, discharging its contents, or 
absorption of the liquid with inspissation and a pseudo-caseous form of 
degeneration may result. Finally, the degenerated area may become 
calcareous. 

Pigmentation may follow acute inflammations or traumatism of 
the glands, the extravasations of blood occurring in such conditions 

leading to hematogenous pigmenta- 
tion. The blood-pigment occurs in 
granular masses within the cells of 
the stroma or within the lymphatic 
cells themselves. Blood pigmentation 
may also occur in the glands adjacent 
to areas of hemorrhagic extravasation, 
the pigment in such cases reaching 
the glands through the lymphatic 
vessels and being deposited in the 
lymph-sinuses, or even in the follicles 
and cords. Analogous pigmentation 
from external sources may result from 
tattooing, and occurs regularly in the 
bronchial glands as the result of 
the inhalation of various dust-particles which penetrate the walls of the 
bronchioles and alveoli, and eventually find their way to the bronchial 
glands through the lymphatic stream (anthracosis) (Fig. 193). The glands 
may be completely black in such cases, and the lymphatic circulation 
through them may be obliterated. Secondary inflammatory changes 
result in most cases (see p. 472). 

INFLAMMATION— LYMPHADENITIS 

Acute lymphadenitis is commonly secondary to inflammations in 
the neighborhood, the irritants being carried by the afferent lymph- 
atics. Sometimes direct extension of inflammation by contiguity of 
structure may lead to involvement of the lymphatic glands. Occa- 
sionally lymphadenitis is seemingly primary in cases in which the in- 
fective irritants have caused no lesion at the portal entrance to the 
body. 




Fig. 193. — Anthracosis of a bronchial 
lymph-gland (Orth). 



DISEASES OF THE LYMPHATIC TISSUES 



471 



Pathological Anatomy. — The glands become enlarged, hyperemic, 
and considerably infiltrated with liquid. When the inflammation is 
intense there may be minute hemorrhages. Microscopically, the lymph- 
sinuses are found distended with cells — leukocytes, red blood-cells, and 
proliferated and desquamated endothelial cells from the lining membrane 
of the sinuses. The changes in the sinuses are spoken of as "sinus 
catarrh." The proliferated lining endothelial cells in some places domi- 
nate the field. They may have more than one nucleus; they are actively 
phagocytic. The follicles and cords are increased in size from infiltration 
and probably also from proliferation of the lymphoid cells. The process 
may become arrested and resolution to the normal condition may ensue. 
If mild inflammation of this character has continued for a great length of 
time, or if the condition is repeated, hyperplasia of the trabecular connec- 
tive tissue, of the blood-vessels, and of the capsule of the gland may 
lead to a termination in chronic enlargement and induration of the 
glands. 

In cases of greater intensity of the infective cause, necrotic or sup- 
purative changes may occur. In the cases of necrosis such as occur 
in typhoid fever and in diphtheria there may be noted small spots of 
yellowish-white color in the hyperemic glands, and subsequently these 
undergo well-marked necrosis. Complete necrotic softening and even 
rupture of the gland may ensue, or, if the necrosis remains limited in 
extent, inspissation and sometimes calcification may terminate the 
process. 

Suppurative lymphadenitis is not uncommon. It is seen in the 
glands below Poupart's ligament in cases of infective wounds of the 
leg ; in the inguinal glands as a result of chancroid or gonorrheal urethri- 
tis; in the glands of the neck in association with diphtheritic, scarlatinal, 
or other inflammations of the throat, or following erysipelas; in the 
axillary glands as a result of wounds of the arm; and in the internal 
lymphatics in various infective diseases. The term bubo is applied to 
suppurative lymphadenitis of superficial glands. Of particular interest 
is the tendency to this condition in the plague of the East, or the bubonic 
plague (q. v.). 

Pathological Anatomy. — The changes noted in the gland at the out- 
set are similar to those in the simple inflammations, but under the 
microscope a greater accumulation of leukocytes is apparent, and the 
gland tends to soften, with the formation of more or less creamy pus. 
The capsule may prove resistant for a time, and reactive inflammation 
around it may establish an additional wall. A single gland of a group 
may be affected, but more commonly the several glands are together 
involved. Eventually rupture may take place, but in instances in which 
the process has been circumscribed, inspissation of the pus and, finally, 
calcification may occur. 

In the most intense forms of lymphadenitis hemorrhagic or gan- 
grenous conditions are developed. These acute inflammations usually 
have associated with them an infiltration and edema in the surround- 
ing tissues (perilymphadenitis) . 

Chronic lymphadenitis leads to induration with enlargement. 
It occurs as the result of repeated acute attacks or in consequence of 



472 



A TEXT-BOOK OF PATHOLOGY 



long-continued irritation by particles carried to the lymphatic glands 
from some focus of disease. 

Pathological Anatomy. — As a rule, the^process affects the connective- 
tissue elements of the gland in particular, and there results a consider- 
able amount of induration, sometimes associated with atrophy or 
necrosis of the proper lymphoid structure. Occasionally, however, the 
lymphoid elements themselves are hyperplastic, and the normal relation 
of fibrous tissues, follicles, and medullary cords is preserved. 

Microscopically, the overgrowth of the connective tissue springing 
from the trabecule, around the blood-vessels, and of the reticulum of the 
pulp is apparent. This may consist of round cells and fibrous connective 
tissue, or there may be a tendency to the formation of epithelioid cells 
and even giant cells. 

Pathological Physiology. — -Inflammations of the lymphatic glands 
are the result of the arrest of irritants of various sorts carried to the 
glands in the lymphatic channels. This arrest not unlikely serves 
the purpose of a protection against general dissemination of irritants 
and may be of great importance in this way. Complete occlusion of 
the lymph-sinuses by deposition of solid particles (as coal-dust) or by 
disease of the glands may obstruct the lymphatic flow entirely, and 
a retrograde inflammatorjr process may result from the damming back 
of infected lymph or from extension of disease along the lymphatic 
channels. 

INFECTIOUS DISEASES 

Tuberculosis of the lymphatic glands is due in nearly all cases to 
infection by bacilli reaching the gland through the afferent lymphatics, 
though occasionally hematogenous infection occurs. Under the heading 
"tuberculosis" we must include what the older writers designated as 
scrofulous glands, for in the majority of such cases, if not in all, the 
disease is essentially tuberculosis, though the mode of infection is not 
always apparent. 

Pathological Anatomy.- — The first visible change is the formation of 
small grayish nodules in the gland, and sometimes the eruption of these 
is attended with hyperemia and inflammation. Later, these tubercles 
increase in size and undergo caseous changes (Fig. 195) as eslewhere, 
and eventually the entire gland may be converted into a cheesy mass, 
which may liquefy and not rarely discharges through the ruptured cap- 
sule. By reason of the tendency to reactive inflammation of the capsule 
or a penetration of it by the tuberculous process, groups of glands are 
usually found rather tightly bound together and the softening, when it 
appears, affects the whole mass. Microscopically, the first appearance 
is that of gray tubercles containing giant cells and epithelioid cells, sur- 
rounded by a zone of round cells (Fig. 194) . Later, the characteristic appear 
ances of hyaline transformation and of caseation are observed. The end 
result of this process is either a caseous abscess, discharging creamy pus, 
or a cicatrizing chronic inflammation from which the g.and is transformed 
into a firm yellowish- white, tough, fibrous mass; calcareous change is 
common. Sometimes the glands in tuberculosis become enlarged and 



DISEASES OF THE LYMPHATIC TISSUES 



473 



harder than normal, and present areas of grayish color, but do not tend 
so markedly to undergo necrosis. In these instances the microscopical 




Fig. 194. — Tuberculosis of lymph-gland, showing early miliary tubercle and hyaline 

connective tissue. 

examination presents foci composed for the most part of epithelioid cells, 
and much less abundant in round cells than are tuberculous tissues as 




Fig. 195. — Tuberculous lymphatic gland: a, a, Recent tubercle with giant cell (c, c); 
ai, caseous tubercle with giant cell (ci); b, b, b, lymphadenoid tissue; d, d, d, epithelioid 
cells (Ziegler). 



474 



A TEXT-BOOK OF PATHOLOGY 



a rule (Fig. 196). Giant cells may be wanting, or a few may be found on 
prolonged search. The histological picture in these cases somewhat 
suggests sarcoma, and the clinical as well as pathological findings have 
led some to regard cases of this type as Hodgkin s disease, and to conclude 
that Hodgkin's disease is really a form of tuberculosis of the lymphatic 
glands. 

Scrofula.- — The tuberculous nature of scrofulous lymphadenitis 
was first shown by demonstrations of the infectiousness of the soft- 
ened glandular material when injected into animals. The micro- 
organisms themselves may be demonstrable in the earlier stages in the 
epithelioid or giant cells, or lying between these; but when the process 
is at all advanced it is extremely difficult or impossible to demonstrate 
bacilli. 




Fig. 196. — Tuberculous lymphatic gland: a, a, Lymphadenoid tissue; b, b, large round 
cells (epithelioid); c, c, large spindle cells (Ziegler). 

Individual Groups of Glands. — Among the more commonly affected 
groups of glands are the cervical (Fig. 197), the bronchial, and the 
mesenteric. Tuberculous cervical glands occasion considerable tumors 
in the neck, and it is these in particular that have been classified as 
scrofulous. Not rarely they advance to complete softening and rupture 
on the surface. Sometimes, however, they penetrate deeply, and may 
rupture into the trachea or esophagus, or into the pleural cavity. The 
mode of infection is rarely apparent, but in many cases no doubt the 
micro-organisms enter through the mucosa of the mouth or pharynx, 
or the tonsils, where they may or may not first occasion specific lesions. 

The bronchial glands are affected very frequently in cases in which 
the bacilli, entering through the lungs, have left no trace of tubercu- 
lous disease at the portal of entrance; while in cases of actual tubercu- 
losis of the lungs the bronchial glands are quite constantly involved 
(Fig. 198). The glands are usually cheesy and may become calcareous, 
but softening not rarely occurs. Perforation of one of the bronchi may 
lead to acute bronchogenetic tuberculosis of the lungs; or the softened 
gland may discharge into a large vein and thus occasion disseminated 
miliary tuberculosis. 



DISEASES OF THE LYMPHATIC TISSUES 



475 




Fig. 198. — Tuberculous lymphatic glands at the bifurcation of the trachea (from a speci- 
men in the Museum of the Philadelphia Hospital). 



476 



A TEXT-BOOK OF PATHOLOGY 



The mesenteric glands are especially involved in children, this 
condition being known as tabes mesenterica. The infection occurs 
through the intestinal tract, and has sometimes been shown to be due 
to the ingestion of infected milk or meat. The intestines may first 
suffer, or the bacilli may penetrate the intestinal mucosa without causing 
local lesions. 

Syphilis. — Enlargement of the lymphatic glands may occur in the 
vicinity of the initial lesion during the primary period; and is habitually 
present in all parts of the body during the secondary period, the post- 
cervical, axillary, inguinal, and epitrochlear groups being most character- 
istically involved. The glands are hard, and do not tend to soften or 
suppurate. Microscopically, there is found proliferation of the con- 
nective-tissue elements throughout the gland, with some endothelial 
hyperplasia, giving pictures very suggestive of tubercles minus giant cells. 
In all stages an increase of reticulum cells and perivascular round cell 
increase are quite prominent. 

In the tertiary period gummata (bubo tertiaris) may be observed, 
especially in the lymphatic glands adjacent to the diseased viscera. 

Leprosy and actinomycosis occasionally involve the lymphatic 
•glands. (See General Pathology.) 

LEUKEMIA AND HODGKIN'S DISEASE 

It is difficult to classify these diseases, which in some respects appear 
to be related to pure hypertrophies, while in other features they suggest 
infections. Finally, there are certain facts which indicate a close kinship 
with tumors, as, for example, the similarity in histological features, 
the malignant nature of the diseases, the wide-spread lesions (metastasis?), 
and the fact that certain accepted tumors (chloromata) are accompanied 
by a leukemic character of the blood. For all of these reasons leukemia 
and Hodgkin's disease are here considered between hypertrophy and in- 
fections on the one hand, and tumors on the other. 

Leukemia. — The lymphatic glands are especially involved in the 
type of leukemia designated lymphatic, which usually, if not always, 
originates in the lymphatic glands. The view formerly held by many 
that all forms of leukemia originate in the bone-marrow was based upon 
an erroneous interpretation of the derivation of the cells in the blood 
and bone-marrow in certain cases. These cells, instead of being lympho- 
cytic, were myelocytic in nature, and the supposed lymphocytic process 
is now recongized as myelocytic or myeloblastic. 

The glands in lymphatic leukemia may be uniformly large in all 
parts of the body, or those of certain groups, such as the cervical, axillary, 
mediastinal, or inguinal, may be specially involved. Macroscopically, 
the glands are usually fairly firm, sometimes quite hard, or in acute cases, 
soft; are not greatly fused together when a whole group is affected; and 
on section the substance presents a grayish, pinkish to yellowish color. 
Areas of softening or hemorrhage may occur in exceptional cases. 

Histologically, the whole gland is uniformily infiltrated with lympho- 
cytic and lymphoblastic cells closely packed together and eradicating 
all signs of the normal structure of the gland (follicles, medullary 
cords and sinuses) . Sometimes the gland may be only partially involved, 



DISEASES OF THE LYMPHATIC TISSUES 



477 



and the unaffected portion may then exhibit more or less normal histo- 
logical features. The walls of small blood-vessels are frequently pene- 
trated by the lymphocytic proliferations, which perhaps accounts for 
the entrance of the cells into the circulating blood. Similar histological 
features are found in the spleen and bone-marrow, and to a less extent 
in the liver and various other organs. 

Certain investigators have described cases with precisely the same 
histological features, but without the leukemic blood-picture, and have 
proposed names such as aleukemic lymphadenia or lymphadenosis. That 



Fig. 199. — Hodgkin's disease, showing marked enlargement of the glands of the right 
axilla, with consequent dropsy of the arm; less marked involvement of the submaxillary, 
cervical, and inguinal lymph-glands. 

such cases may occur is easily understood when it is recalled that the 
blood-picture may become practically normal, either spontaneously or 
under treatment, without any notable change in the size of the glands or 
spleen. 

Hodgkin's Disease. — -It is difficult to define this affection accu- 
rately, either clinically or pathologically, though a certain histological 
picture seems to be fairly distinctive (Plate 7). 

Macroscopically, Hodgkin's disease presents considerable enlarge- 
ments of certain groups of lymphatic glands, notably the cervical, 
axillary, and inguinal. Other groups may, however, be similarly in- 




478 



A TEXT-BOOK OF PATHOLOGY 



volved. The glands are more or less fused together, though rarely to a 
single uniform mass. Exceptionally, the glands may be quite separate 
from one another. On section, the substance is more or less firm, of 
yellowish or grayish color, and not infrequently exhibits areas of necrosis. 
Histologically, there are found numerous elongated (fibroblastic?) 
cells, often arranged in a somewhat trabecular manner, between which 
lymphocytic elements are found in variable abundance. In some cases 
the most striking feature of the histological picture is the large number 
of eosinophile cells seen in the section. Giant cells are sometimes fairly 
numerous. There is a fine fibrosis between the cells. Here and there 
will be found a large palely staining cell like a large endothelial cell, 
sometimes with more than one nucleus or occasionally a ring of nuclei, 
suggesting an origin from the compression of a lymph-channel (for 
full discussion see page 193). 

Similar histological features are observed in the lesions of the spleen 
and liver met with in Hodgkin's disease. 

TUMORS 1 

LYMPHOMA, LYMPHADENOMA LYMPHOSARCOMA 

Lymphoma or lymphadenoma is a benign tumor affecting the 
lymphatic glands of a single group, or occurring in a more generalized 
form. Masses, sometimes of considerable size and of variable con- 
sistency (hard and sojt lymphoma), are formed, but the process does not 
extend to surrounding tissues nor by metastasis to distant parts. Histo- 
logically, the growth presents the usual features of lympha'denoid 
tissue with more or less conspicuous hyperplasia of the reticular cells 
and endothelia in some cases (hard lymphoma). 

It is extremely difficult to differentiate these growths from chronic 
lymphadenitis or lymphatic hypertrophy. The basis on which the 
distinction is made is rather the absence of adequate cause and the 
excessive growth of the glandular enlargements than any histological 
features. It must be recalled that very marked enlargements of lym- 
phatic glands may be found in the neck or elsewhere in association with 
long-continued irritations, such as bad dentition or oral infections. In 
these cases it is .difficult to determine whether the glandular process is 
inflammatory, infectious,. or neoplastic. 

Lymphosarcoma differs from lymphoma mainly in its manifest 
tendency to extend beyond the limits of the affected gland or group of 
glands to surrounding structures, and by metastasis to various parts of 
the body. The histological structure differs from that of lypmhoma 
only in the less typical features of lymph-gland architecture. There 
is less differentiation of follicles, sinuses, and a more uniform undiffer- 
entiated lymphadenoid structure. Lymphosarcomata are especially 
common in early life, and occur in the cervical glands, tonsils, and 
mesenteric glands. Chloroma (see pp. 197 and 483) is a closely allied 
form of growth characterized by its greenish color. 

Endothelioma of the lymph-glands may occur, according to Ewing, 
but it is difficult to determine in any given case whether it be truly 

1 See also page 191. 



PLATE 7 





.. *' . « * 










'Mb . - 






















f ti^" 



Hodgkin's disease of the Reed type. The illustration shows various stages of the 
disease process. In the upper left corner there is hyperplasia of large epithelioid cells 
among the small lymph-cells. To the right of this, in what is probaby a sinus, there 
is hyperplasia of the large mononuclears, an excess of eosinophils, fibroblasts, and fibers. 
Below these two sections of the picture are found masses of large mononuclears, sepa- 
rated by a connective-tissue framework, in which are also polymorphonuclears, eosino- 
phils, and polynuclear cells. At the bottom there is great increase of the fibrous tissue 
surrounding and distorting the cells. 



DISEASES OF THE LYMPHATIC TISSUES 



479 



neoplastic or secondary to a granulomatous disease of the nodes. A 
long-continued inflammation of the gland may occasion a neoplastic 
growth of the endothelium and overshadowing or obliteration of the 
lymphadenoid tissue. 

Sarcoma. — Other forms of sarcoma are sometimes met with as 
primary localized new growths of the lymphatic glands. Such are not 
rarely seen in the mediastinum. In these instances the capsule of the 
gland is penetrated and local extension to neighboring glands and other 
surrounding structures is commonly observed, but the entire group of 
glands is not, as a rule, affected. General metastasis may occur, but 
affects the larger organs rather than the lymphoid tissues. Round- 
cell, spindle-cell, alveolar sarcoma, and endothelioma are the forms 
described. Secondary sarcoma occasionally involves the lymphatic 
glands. 

Carcinoma is always secondary, the regional lymphatic glands being 
the most frequent seat of secondary cancer. The metastatic deposits 
are first seen in the peripheral lymph-sinuses of the gland, but later 
enlarge and may invade the whole gland or spread beyond the capsule. 

Secondary tumors of lymph glands are common and may occur in all 
kinds of new growths but more frequently from carcinomata since these 
spread chiefly along lymph channels. Reaching the sinuses, metastatic 
emboli proliferate around follicles or in the central medullary zone, 
growing in a very atypical fashion. It is often not possible to determine 
the exact type of the original carcinoma because it is not necessarily 
repeated in metastasis. For example glands involved from scirrhous 
cancer of the breast may have the formation of a medullary or adeno- 
carcinoma. There is however a tendency to form fibrous tissue about 
secondary growths. 

Bone-Marrow 

Anatomical Considerations. — The marrow of the bones is a tissue 
composed of a reticulum of connective-tissue cells, supporting a rich 
network of capillaries and venules of unusual width. The cells proper 
of the marrow are rounded and vary greatly in size. They contain a 
clear nucleus, a slightly acidophilic protoplasm, and many of them 
neutrophilic granules. In addition to these myelocytes there are occa- 
sional giant cells (megakaryocytes or myeloplaxes) lying near [the bony 
trabecule; also nucleated red corpuscles, non-nucleated red corpuscles, 
and large cells enclosing corpuscles. After the first few years of life 
the marrow of the long bones loses its reddish color and becomes more 
or less yellow, and there is then found, microscopically, a great pre- 
ponderance of fat-cells. The marrow of the vertebrae, sternum, ribs, 
and other flat bones remains more or less red throughout life, and 
islands of red marrow tissue may also be found in the marrow of the long 
bones in later years. 

The marrow cells are descendants of the endothelial cells of blood- 
vessel walls. From these are derived somewhat large rounded cells 
containing a relatively large nucleus and having a basic non-granular 
protoplasm. These cells, termed myeloblasts, are the mother-cells from 



480 



A TEXT-BOOK OF PATHOLOGY 



which the myelocytes (neutrophilic, eosinophilic, and basophilic) take 
their origin. This stage of the process of marrow-cell and blood forma- 
tion is seen only in the latter months of fetal life and for a short time 
after birth; and pathologically in certain diseases affecting the blood. 
Soon after birth the myeloblasts are no longer found, and the myelocytes 
then represent the earliest phase in the process^ of leukocyte formation. 

The red blood-corpuscles of the blood also trace their origin from 
the endothelial cells of blood-vessels. In the fetal marrow and under 
certain pathological conditions in later life may be found certain large 
hemoglobin-containing cells with a large pale nucleus (primary erythro- 
blast or megaloblast) which are probably direct derivatives of the endo- 
thelial cells. In later periods of life a rounded, basophilic cell, containing 
a rather small and dark-staining nucleus, is the intermediary stage be- 
tween the endothelial cell and the hemoglobin-containing erythroblasts. 
The latter also contain a darker and smaller nucleus than that of the 
"primary erythroblast." In the ultimate formation of non-nucleated 
red cells the nuclei of the erythroblasts undergo a process of pyknosis 
and karyorrhexis. The older idea of nuclear extrusion is probably 
incorrect. 

There are, about blood vessels and in separate groups, collections of 
small deeply staining mononuclear cells like small lymphocytes, which 
indeed they probably are. The platelets of the blood are derived from 
the megakaryocytes by pinching off of part of their cytoplasm. 

After destruction of bone marrow by inflammation or intoxication 
there appear accumulations of the special formative cells itemized above, 
within and around which the adult or completed forms, destined to 
migrate into the blood and tissues, gradually develop. Endothelioid 
cells of the usual type likewise are actively hyperplastic but do not take 
part in blood production, this being performed by such formative elements 
as may be left after the injury. 

There are in the tissue spaces of all the parenchymatous organs, 
small collections of cells, mononuclear in character, which seem to be able 
in times of infection and blood destruction, or under the influence of the 
cause of leukemia, Hodgkin's disease and a few simular conditions, to 
multiply and assume a histology similar to the bone marrow; such groups 
may also be found in the spleen occasionally. 

Some of these are strictly lymphoid in character while others exhibit 
more cells of the myeloid series . There has been much discussion as to the 
origin of these visceral nodes, whether they appear by stimulation of cells 
already present or by migration from the bone marrow. Both methods 
are possible; certainly the first holds true in some lower animals. 

In addition to the important role of blood formation the bone-mar- 
row doubtless also plays some part in the defensive processes against for- 
eign invaders. The large giant cells are occasionally greatly increased in 
size and number and exhibit active phagocytic properties in conditions 
attended with marked leukocytosis; myelocytes are greatly increased 
in number in certain infections, and sometimes myeloblasts become 
conspicuous. Finally, a more or less mechanical role may be indicated 
by the lodgment of large numbers of malarial plasmodia or other micro- 
organisms in the marrow. 



DISEASES OF THE LYMPHATIC TISSUES 



481 



DEGENERATIONS 

Fatty Infiltration. — The fat which occurs normally in the marrow 
may be excessively developed in conditions of general obesity, but also 
at times in marantic individuals, or as a result of atrophy of the bony 
tissues. 

Mucoid degeneration is occasionally seen, and necrosis may form 
a part of the processes of inflammation. 

Pigmentation occurs in the bone-marrow in cases of destruction of 
blood, as in malaria or various hemolytic toxemias. 

ATROPHY 

Atrophy of the bone-marrow is not infrequent in old age or in 
marasmic conditions. With this atrophy there may occur a gelat- 
inous or mucoid transformation. In such conditions as ostitis fibrosa, 
Paget's disease and osteomalacia, a loose irregular fibrous tissue takes 
the place of the thick marrow at the epiphyses. 

HYPERTROPHY 

Hypertrophy of the bone-marrow occurs in various conditions in 
which an increased functional activity is required (1) to replace the 
cellular elements of the blood in case of hemorrhage or blood destruc- 
tion, or (2) to provide greater numbers of certain cells in cases of infec- 
tion. The gross appearance of the bone-marrow and its histological 
features differ considerably in different cases. 

In anemic conditions resulting from repeated losses of blood or from 
hemolytic agencies the bone-marrow frequently exhibits a change from 
the adult (yellow or fatty) to the fetal or infantile type. In extreme cases 
the marrow of the long bones may be uniformly altered and sometimes is 
quite dark red in color; in less pronounced cases islands of pink or red- 
dish color are scattered through the unaltered fatty marrow. The 
highest grade of transformation is seen in typical instances of pernici- 
ous anemia. Histologically, the marrow in the affected areas contains 
numerous nucleated red cells, many with mitotic nuclei, and also many 
myelocytes of different types and sometimes the primary myeloblasts. 
In pernicious anemia, in addition to these elements, there are found the 
primary erythroblasts or megaloblasts, and the spleen, liver, and lym- 
phatic glands may contain areas of myeloid (myelocytic) tissue. The 
sharp distinction between various milder anemias and pernicious anemia 
here suggested is difficult to establish in many cases, and all investigators 
are not in agreement that there is a fundamental distinction, some 
holding that the marrow changes differ only in degree. 

'In infectious conditions, such as typhoid fever, pneumonia, strep- 
tococcus and staphylococcus infections, the marrow is the seat 
of marked changes. Areas of necrosis, degenerative changes in the 
blood-forming cells, and edema indicate the destructive effects of the 
infection, while hyperplastic processes are evidenced by large numbers of 
myelocytes, sometimes (especially in typhoid fever) myeloblasts and 
large numbers of phagocytic cells (megakaryocytes). Similar combina- 
tions of necrotic or degenerative processes and compensatory hyperplasia 
are found adjacent to metastatic tumors invading the bone marrow. 

31 



482 



A TEXT-BOOK OF PATHOLOGY 



The Bone=marrow in Leukemia. — The pathological changes in 
the bone-marrow as well as in other situations (liver, spleen lymphatic 
glands) are difficult to classify, but are included under the heading hy- 
pertrophy because the conspicuous features in the histological changes 
is the hyperplasia of the blood-forming cells. It is difficult, however, to 
distinguish the lesions of the marrow from those in certain conditions 
quite generally recognized as tumors (myeloma, chloroma), and even 
the composition of the circulating blood ma}^ be quite the same in some 
of these cases (chloroma) as in typical instances of leukemia. 

The bone-marrow in myelogenous leukemia presents a variegated 
appearance. Sometimes it is -reddish, more often grayish or mottled, 
and occasionally quite yellowish (pyoid). Histologically, the conspicu- 
ous feature is the abundant hyperplasia of myelocytic cells. These, 
like the myelocytes in the circulating blood, may vary considerably 
in their size and staining reactions. The typical neutrophilic myelocytes 
are most abundant, but eosinophilic and basophilic forms, as well as 
non-granular cells and occasionally forms containing two different sorts 
of granules, may be observed. The red-corpuscle-forming elements are 
rather inconspicuous even in comparison with normal bone-marrow. 
In myeloblasts leukemia (formerly designated acute lymphatic leu- 
kemia) the basophilic myeloblasts form the predominating histological 
element. 

The secondary foci of leukemic change (seen in the spleen, liver- 
lymphatic glands, and in various other organs) have a similar structure 
and represent local hyperplasis of marrow cells — either metastatic or 
originating locally from reversion of endothelial cells of the blood- 
vessels to their embryonal condition and potency. 

In lymphatic leukemia the bone-marrow may present a quite similar 
macroscopical appearance, but histologically the myeloid elements are 
inconspicuous, while lymphoid cells constitute the bulk of the patho- 
logical areas. (See further under Lymphatic Glands.) 

INFLAMMATION 

Osteomyelitis, or inflammation of the marrow, is infectious in 
nature, and may occur in the course of various diseases, such as typhoid 
fever, relapsing fever, small-pox, septicemia, and the like; or as a result 
of traumatism and direct infection. Staphylococci and the typhoid 
bacillus (in typhoid cases) are the most frequent organisms encoun- 
tered. The marrow disease may be the only expression of an infection 
which has arisen in an obscure manner (cryptogenetic osteomyelitis) . In 
the cases occurring in the course of infectious diseases the changes are 
comparable to those which occur in the spleen under the same circum- 
stances. The marrow assumes a redder color than normal, and it may 
be studded with punctate hemorrhages. In other cases areas of necrosis 
and granular degeneration of the cells may be present, and increased 
numbers of white blood-corpuscles may be discovered. Large phago- 
cytic cells may be conspicuous. Sometimes the marrow is quite purulent 
(See Diseases of Bone.) 



PLATE 8 




DISEASES OF THE LYMPHATIC TISSUES 



483 



TUMORS 

The bone-marrow may be invaded by extension of tumors involving 
the bone, or may be the seat of metastatic growths, especially carcinoma. 
Greater interest, however, attaches to the primary tumors of the bone- 
marrow, which may be included under the general terms "myeloma" 
and "chloroma.'' 

Myeloma. — This occurs in the form of multiple primary growths 
involving the vertebrae, ribs, and, somewhat less frequently, the long and 
flat bones. The growths are grayish, yellow, and sometimes pink or 
quite deep red in color; sometimes by confluence a uniform growth 
occupies the whole marrow cavity. The surrounding bone sometimes 
becomes eroded and spontaneous fractures may occur. Histologically, 
myelomata are usually composed of myelocytes (granular or non- 
granular), but in some cases have been made up entirely of plasma-cells 
(plasmocytoma) . In rare instances erythroblasts may be conspicuous. 
Sometimes the tumor is greenish (myelocytic chloroma). The blood 
in myeloma rarely if ever presents leukemic features, but a striking 
clinical feature is the presence of Bence- Jones, albumin in the urine. 

Chloroma. — This term is applied to tumors presenting a greenish 
appearance on section, and involving the bone-marrow as well as the 
lymphatic glands, thymus, and the lymphatic tissues along the gastro- 
intestinal tract. The periosteum of the bones of the head and face is 
an especially common seat. Histologically, two forms may be distin- 
guished: a lymphoidal, in which large lymphocytic cells make up the 
substance of the growth, and a rarer form, the myelocytic, in which the 
cells are of the bone-marrow type. The cause of the green color is 
unknown. Sometimes parts of the growths or certain of the metastases 
fail to present the green color seen elsewhere. An interesting feature 
is the leukemic character of the blood, which suggests the close relation- 
ship of leukemia to processes manifestly neoplastic. 

Sarcomata of giant cells or bony type may involve the marrow, the 
former really arising from it, the latter being only secondary within 
it. The distinctions which should be made have been discussed 
on page 206 and mention is only made here to emphasize the relative 
benignancy of myeloid sarcoma. 



CHAPTER III 



DISEASES OF THE CIRCULATORY SYSTEM 
The Heart 

Development of the Heart. — -At the earliest period of fetal life the 
heart is represented by a hollow tube, lying toward the ventral aspect 
of the neck. Later this assumes an S shape, and still later a transverse 
constriction marks the position which the auriculoventricular grooves 
subsequently occupy. Finally, vertical grooves divide the lateral 
halves into the respective auricles and ventricles; and the truncus 
arteriosus, which is at one of the ends of the primitive tube, becomes 
divided into two parts, forming the pulmonary artery and aorta. The 
separation of the cavities within is accomplished by the outgrowth of 
septa springing from the walls of the primary cavities. The septum 
dividing the ventricles is the first to appear, and springs forward from 
the posterior wall. Next a budding is seen in the position which is later 
occupied by the tissue between the auriculoventricular orifices of the two 
sides ; still later the auricular cavity is divided into two parts by a process 
beginning at the lower and posterior part. The septum which divides 
the truncus arteriosus is essentially connected with or is a part of the 
septum which separates the ventricles. All of these changes begin 
from the seventh to the ninth or tenth week of fetal life. 

Anatomical Considerations. — The heart consists of three layers — 
the endocardium, muscular layer, and pericardium. The endocardium 
is the inner lining of the organ, and is composed of a layer of endothelial 
cells resting upon a stratum of connective tissue. It is continuous with 
the lining membrane of the arteries, and by duplications forms the 
valves. The muscle of the heart is arranged in layers which run in differ- 
ent directions — circular, longitudinal, and obliquely. There is no con- 
tinuity of the musculature of the auricles with that of the ventricles 
except in the case of the special muscle cells, which will be mentioned 
presently. The muscle of the two sides of the heart is in part con- 
tinuous. Thus both auricles and both ventricles have certain muscle 
layers in common, but in part, especially in the ventricles, the muscula- 
ture is wholly independent. 

In recent years much attention has been given to a separate system 
of muscle cells or fibers (the Purkinje cells) which are found just be- 
neath the endocardium in the auricles and ventricles. They are now 
known to make up a well-ordered system which begins with the sub- 
endocardial fibers in the right auricle where it is spread out widely. At 
the auriculoventricular junction it becomes contracted to a narrow band 
or cord (the bundle of His) which passes downward into the interven- 

484 



DISEASES OP THE CIRCULATORY SYSTEM 



485 



tricular septum, in the upper part of which it divides into a right and 
left branch. These branches run to the respective ventricles and their 
fibers spread out under the endothelium, and eventually extend to all 
parts of the musculature. This system, composed of somewhat less 
completely differentiated muscle cells than those of the body of the heart, 
is concerned with the conduction of impulses of contraction from the 
auricle to the ventricle. At two positions there are found nodes or 
massed cells of this tissue — one in the wall of the right auricle adjacent 
to the mouth of the superior cava, the other at the auriculoventricular 
junction. The former is now recognized to be the site where the rhyth- 
mic impulses that occasion the cardiac contractions originate. 

The fibers of the heart muscle are peculiar in being branched and in 
being devoid of a sarcolemma. The pericardium resembles the endo- 
cardium in structure. 

The blood-vessels supplying the heart muscle are branches of the 
coronary arteries. They divide and subdivide, and afford abundance of 
blood proportionate to the needs of so active an organ. Anastomosis be- 
tween the ends of the myocardial vessels is by no means perfect, so that 
infarcts occur the more easily. The lymphatic system is equally de- 
veloped. The nervous system includes numerous ganglionic centers in 
the furrows between the ventricles and between the auricles and ven- 
tricles. Other ganglion-cells are found within the muscle itself. 

Details regarding the gross structure of the organ need not be men- 
tioned here. The weight of the heart in the adult male is about 300 gm., 
in the adult female about 250 gm. The volume of the entire organ in 
the adult male is about 290 to 310 c.c, in the adult female about 260 
to 280 c.c. 

CONGENITAL DISEASES AND DEFORMITIES 

Abnormalities of the heart may be discovered in the newborn and 
are the result of developmental defects or, less commonly, of fetal endo- 
carditis and myocarditis. The older pathologists attributed to inflam- 
matory changes many of the conditions which more accurate knowledge 
of the development of the heart clearly indicates are the result of defects 
in development. 

Abnormality of Position. — The heart may retain its position high 
up toward the cervical region, and may even be entirely in the neck. 
Occasionally it is completely exposed or, merely covered with peri- 
cardium, lies immediately beneath the skin, the sternum in such cases 
being divided in the middle line. Sometimes it lies beneath the skin of 
the abdomen. 

Abnormality in Size. — Congenital smallness, or hypoplasia, of the 
heart and aorta is occasionally observed. Particular attention has been 
called to this condition in cases of chlorosis (see p. 449). 

Defective Development. — There may be complete absence of the 
heart in acardiac monsters. Sometimes the septa dividing the auricles 
and ventricles are wholly wanting and a bilocular heart results; or the 
auricular septum alone is absent, when the organ is trilocular. More 
commonly than these conditions, the organ is completely reversed 
lying on the right side of the body and having the blood-vessels entering 



486 



A TEXT-BOOK OF PATHOLOGY 



it and leaving it reversed, so that the general venous blood enters the 
left auricle, the pulmonary blood the right auricle, while the aorta 
springs from the right ventricle and the pulmonary artery from the 
left. This condition is spoken of as dextrocardia. The abdominal vis- 
cera may be reversed at the same time, the liver being on the left and 
the spleen on the right side (situs inversus). Other abnormalities in 
the arrangement and origin of the great blood-vessels, such as an un- 
divided truncus arteriosus, are rare. 

Stenosis and atresia of the pulmonary artery result from abnormal 
situation of the septum which divides the truncus. Complete atresia 
is very rare. Stenosis is one of the commonest developmental defects of 
the heart, and in some cases is due to fetal myocarditis about the orifice. 
It may involve the root, the conus, or the trunk of the vessel. The 
septum of the ventricles is usually defective and the foramen ovale re- 
mains patulous. When the stenosis is considerable the pulmonary cir- 
culation is often maintained by the persistence of the ductus arteriosus 
botalli, and the right ventricle is greatly hypertrophied. 

Stenosis and atresia of the aorta are less frequent than the same 
conditions affecting the pulmonary artery They arise from the same 
cause, and are usually accompanied by the same defects of the septa 
and patency of the ductus arteriosus. Stenosis of the trunk of the 
aorta at the isthmus — *. e., at a point between the left subclavian artery 
and the mouth of the ductus arteriosus — is not infrequent in moderate 
degree. More rarely there may be almost complete atresia, or the aorta 
may be entirely wanting at this point. The circulation is maintained 
by collateral anastomosis of the branches of the subclavian with the 
descending aorta. In all of these cases hypertrophy of the left ventricle 
and damning back of blood into the venous system with passive conges- 
tion are usually present. 

Defects of the ventricular septum may be unaccompanied by other 
abnormalities; but, as a rule, they are of secondary importance, occur- 
ring in cases of abnormality of the pulmonary artery or aorta. The 
septum may be completely wanting or there may be partial defects, 
these latter usually lying anteriorly and above, in what is known as the 
membranous portion or the undefended space. 

Defects of the auricular septum are comparatively rare, but a patulous 
condition of the foramen ovale is one of the most frequent of congenital 
affections of the heart. It is due to the failure of the valve of the foramen 
to unite at the edges, as normally occurs some time after birth. Slit- 
like openings are seen very frequently in postmortem examinations, 
while more decided patency is occasionally observed without other 
cardiac abnormalities. This is especially likely to occur when congenital 
atelectasis or some other pulmonary a c ection causes continuance of 
high blood-pressure in the right heart after birth. 

Stenosis and atresia of the auriculoventricular orifices are rare 
congenital conditions, and in the former fetal endocarditis doubtless 
plays an important part. When there is complete atresia the auricular 
septum must remain widely open, and the septum of the ventricle is 
usually deficient and the ductus botalli patulous. 



DISEASES OF THE CIRCULATORY SYSTEM 



487 



Patulous Ductus Botalli. — -This condition is frequent in cases of 
stenosis of either the aorta or pulmonary artery, and serves to convey 
the blood from the patulous artery into that which is obstructed. Like 
the patulous foramen ovale, it may occur as an independent condition 
resulting from congenital atelectasis of the lung which leads to the 
continuance of the fetal conditions of circulation. 

Valvular Defects. — Not rarely there may be but two semilunar 
valves at the aortic or pulmonary orifice, and, on the other hand, four 
may be observed, the latter being a relatively common condition. Simi- 
lar numerical abnormalities occur at the auriculoventricular valves. 
Abnormal length or shortness of the leaflets may also be observed, or 
the segments may be united, forming a complete ring. The latter con- 
dition must not be mistaken for the agglutination of endocarditis. The 
leaflets may be fenestrated. 




Fig. 200. — Congenital cardiac dis- Fig. 201. — Clubbing of the fingers in con- 

ease, showing peculiar thickness of lips genital cardiac disease; from same case as 
and nose (Eichhorst). Fig. 200 (Eichhorst). 

Pathological Physiology. — -Congenital heart diseases occasion 
serious disturbances of the circulation, leading to overfilling of the 
venous channels and often abnormal mixture of the arterial and venous 
blood. In consequence of these conditions blueness or cyanosis is a 
common symptom, and the terms congenital cyanosis and morbus cceruleus 
are applied. The imperfect oxidation of the blood doubtless causes 
profound effects, but these have not as yet received accurate study. 
The imperfect circulation causes certain changes in the tissues, notable 
among which are thickness of the lips and nose, giving rise to a peculiar 
facial expression (Fig. 200) and " clubbing" of the finger ends (Fig. 
201). The blood in congenital cyanosis often contains an excess of red 
blood-corpuscles. (See Polycythemia.) 

CIRCULATORY DISTURBANCES 
Thrombosis of the cavities of the heart results from the causes 
which induce thrombosis elsewhere in the circulatory system. These 



488 



A TEXT-BOOK OF PATHOLOGY 



are, mainly, slowing of the current of blood, some roughness or disease of 
the endocardial lining, and diseased conditions of the blood itself , which 
render it more liable to coagulation. Slowing of the circulation is the 
most frequent cause of intracardiac thrombosis, and leads to the forma- 
tion of the clots found postmortem in cases of gradual death. If the cir- 
culation has been slow for a considerable length of time, there may be 
found more or less grayish or white thrombi in the appendages of the 
auricles or in the ventricles between the muscular trabecule, especially 
near the apex. The formation of these is explained by the gradual 
slowing of the current of blood, which leads to the deposit of the leuko- 
cytes and blood-plaques upon the endocardium and the deposition of 
fibrin. The color may be almost completely white; but if the current 
is almost stagnated, admixture of red corpuscles occurs and pinkish or 
quite red clots (currant-jelly clots) are formed. Of this latter sort are 
the thrombi formed in the heart during the agonal period and post- 
mortem. They are further distinguished from the thrombi formed 
intra vitam by the fact that they are not closely attached to the en- 
docardium and between the trabecular muscles. 

Among the diseases in which the circulation is prone to be sluggish, 
and which are frequently accompanied by cardiac thrombosis, pneu- 
monia, tuberculosis of the lungs, the asthenic fevers, and diseases of 
the muscle of the heart may be named. Dilatation of the chambers 
of the heart and cardiac aneurysm lead to thrombosis by their effect 
upon the rapidity of the circulation either in the general heart-cavity in 
the first, or in the aneurysmal dilatation in the second. Among the 
endocardial lesions which occasion thrombosis the most important is 
acute endocarditis. In this condition there is 
habitually deposited upon the affected part of the 
valves or mural endocardium a capping of fibrin 
deposited from the blood passing over the dis- 
eased area. In chronic endocarditis, especially 
when there are irregular calcareous deposits 
rendering the surface rough and uneven, con- 
siderable thrombotic deposit may occur. 

Pathological Anatomy. — Cardiac thrombi, 
formed some time before death, usually appear 
as deposits upon the heart wall of a yellowish 
or whitish color and rather firmly attached 
between the muscular trabecule. Occasionally 
they have a stratified appearance, due to the 
fact that the circulation varied in rapidity 
during the formation of the thrombi. Secondary 
changes are not rare, the most striking being 
softening of the fibrinous mass in places, with 
the formation of cyst-like cavities varying in size from a split pea to a 
cherry (Fig. 202). Sometimes thrombi project from the endocardial 
surface in a polypoid form and these may present the appearance of 
fibroid tumors. A curious form occurs in the auricles, the thrombus 
presenting itself as a round mass attached to the endocardium by 
fine pedicles or lying entirely free (ball-thrombi, globular thrombi). 




Fig. 202. — Thrombosis in 
cardiac chambers, showing 
cyst-like structure (Orth) . 



DISEASES OF THE CIRCULATORY SYSTEM 



489 



Lesions in Other Organs. — Thrombosis of the heart may occasion 
serious disturbance of the circulation by weakening the heart muscle or 
by obstructing the valvular orifices. The latter is especially common in 
the case of the globular thrombi or the polypoid thrombi of the auricles. 
Passive congestion of the various organs and the secondary changes due 
to this condition follow. Thrombosis may lead to another and more 
serious danger, that of embolism. When portions of the thrombus are 
broken off they are carried into the circulation and lodge in the small 
arteries of the spleen, the kidney, the brain, the lungs, or elsewhere, 
causing infarctions, or, in case micro-organisms be present in the original 
thrombus, metastatic abscesses and pyemia. 

Thrombosis and Embolism of the Coronary Artery. — The 
former condition is much the more common, as the coronary arteries 
are frequently the seat of advanced atheromatous narrowing and rough- 
ening, which predispose strongly to thrombosis; and, on the other hand 
the mouths of the coronary arteries are so placed that emboli are unlikely 
to enter. The lodgment of an embolus seriously compromises the heart's 
action, as has been shown experimentally in animals, and marked patho- 
logical change is, therefore, unlikely to occur before death ensues. When 
a partially obstructing embolus lodges or a thrombus is formed there 
results almost complete anemia of the area supplied by the artery af- 
fected, and, in consequence, an anemic infarct. The muscle-fibers of the 
affected area become hyaline or granular, and do not take the stain 
when subjected to ordinary histological examination. To the naked eye 
the diseased portion presents itself as a white, and later as a yellowish, 
area of softening, and the condition is spoken of as myomalacia cordis. 
It is found most frequently in the anterior or posterior wall of the left 
ventricle, near the apex, from the fact that the descending branch of the 
left coronary artery is the most commonly occluded vessel. Next in 
frequency to these points the anterior portion of the septum is found to 
be affected. Small areas may heal by absorption of the degenerated 
tissue, and by infiltration and proliferation of connective tissue. In 
this manner a scar is formed which may remain, or may subsequently 
lead to aneurysmal dilatation. On the other hand, rupture of the heart 
may be occasioned either with or without the formation of an acute 
aneurysmal dilatation at the degenerated area. 

Diseases of the Endocardium 

The endocardium, both mural and valvular, is subject to edema 
and hemorrhage either independently or as forerunners of inflamma- 
tion. Hematomata have been seen in the valves. Fatty, mucoid, 
hyaline, amyloid, and calcareous changes have been seen. 

INFLAMMATION 

Inflammation of the endocardium, or endocarditis, may be acute or 
chronic; the latter is in most cases merely a continuation of the former. 

Acute endocarditis affects the endocardium of the valves in the 
great majority of cases, but it is sometimes found in the endocardium 
of the cavities of the heart, when it is spoken of as mural endocarditis. 



490 



A TEXT-BOOK OF PATHOLOGY 



Etiology. — Endocarditis is practically always a secondary process, 
and is in nearly all, if not all, cases due to the action of micro-organisms. 
Cold and traumatism, upon which the older writers insisted as causal 
factors, act merely as predisposing causes. Endocarditis occurs most 
frequently in association with acute articular rheumatism. Next to 
this cause, scarlet fever, pneumonia, and various forms of sepsis are 
most important, but in any case of suppurative or infectious disease 
endocarditis is a possible complication. Even the seemingly mild in- 
fections like tonsilitis may occasion endocarditis. It occurs at times 
also in Bright's disease and in conditions of great malnutrition, such as 
carcinoma and certain nervous affections. These cases have been cited 
as opposing the view that endocarditis is always infectious and due to 
micro-organisms. It may be that toxic substances resulting from im- 
proper metabolism act upon the endocardium as do micro-organisms, 
or that portions of the endocardium suffer degeneration as a result of 
depressed nutrition, but it is more probable that terminal or intercur- 
rent infection from some hidden source may occur in these chronic dis- 
eases, with resulting endocarditis. 

As to the micro-organisms themselves, the most important are the 
Staphylococcus pyogenes aureus, the Streptococcus pyogenes, and the 
Diplococcus pneumoniae. A special form of streptococcus distinguished 
by certain rather marked cultural features, the Streptococcus viridans, has 
in recent years been found especially frequent in certain cases of sub- 
acute endocarditis or recurrent endocarditis. There are many forms 
which have been less frequently detected. Among those reported are 
the Staphylococcus pyogenes albus, the Micrococcus endocarditis capsu- 
latus and rugatus, the Bacillus endocarditis griseus and capsulatus, B. 
pyogenes Joetidus, B. coli communis, the B. diphtherial, the B. aerogenes 
capsulatus (Welch), or the bacillus of Achalme, and the bacillus of ty- 
phoid fever. The tubercle bacillus has been found in a few cases, but it 
is generally believed that its presence is explained as a secondary deposit 
rather than as the cause of the endocarditis. The gonococcus has been 
found capable of causing endocarditis. 

The bacteria causing the valvular inflammation settle upon the endo- 
thelium from the blood-stream in all probability, but an infection through 
the base of the valve cannot be entirely excluded. When, by reason of 
toxins circulating in the blood, or forceful impact of the leaflets, due to 
overaction of the heart, or disturbed lymph-supply of the valve stalk, 
the endothelium swells, it forms a favorable settling place for bacteria 
passing over the valve in the blood-stream. When the bacteria have 
become attached they are taken up by the phagocyte power of the 
endothelium. Over such a section of turgid endocardium strands of 
coagulum may appear; this adds another factor favoring bacterial attrac- 
tion by slowing the current at that point. 

In all cases of general infection there is a myocarditis and, as the 
blood- and lymph-supply of the valves are scanty, edematous swelling of 
the free part of the leaflet may arise. From a lesion in the muscle near 
a valve base it is possible that bacteria may spread into the valve stalk. 

Valves are not supplied with blood-vessels, but it has been suggested 
that mild inflammations in early life leave some vascularized scar tissue 



DISEASES OF THE CIRCULATORY SYSTEM 



491 



in which capillaries may serve as avenues to the distal end of the valves, 
where lesions will occur upon a subsequent infection. 

Pathological Anatomy. — It is customary to distinguish two varie- 
ties: a simple or verrucose, or benign endocarditis; and an ulcerative, 
septic, mycotic, diphtheritic, or malignant form; but it seems unnecessary 
at the present time to maintain strictly such a distinction. The cases 
vary in anatomical appearance and in malignancy , but there is no essen- 
tial difference and no sharp dividing line. 

The most common seats, in order of frequency, are the mitral valve, 
the aortic valve, the pulmonary valve, and the endocardium of the 
left ventricle, the left auricle, and the right ventricle. The part of the 
valve first involved is a line running across the leaflet at about a dis- 
tance of 2 mm. from the free edge. It is along this line that the valves 
impinge in closing, and it is probable that the mechanical injury sus- 
tained predisposes to endocarditis. In the cavities the lesions are fre- 



Fig. 203. — Section through a segment of the aortic valve and adjacent parts of the aorta 
and heart, showing vegetations on the aortic valve (magnified): b, Aortic valve segment; 
c, c, vegetations; /', calcareous particles in the base of the aortic valve (Bramwell). 

quently found upon the chordce tendinece, and of the parts of the mural 
endocardium proper most apt to be affected may be mentioned the por- 
tion of the left ventricle near to the septum and the aortic valves, and 
the endocardium of the left auricle on the posterior and outer wall above 
the posterior mitral leaflet. 

The first appearance of endocarditis is that of an area of opacity or 
slight roughness extending in a line across the valve or involving the 
endocardium elsewhere. Later, small nodular elevations, not unlike 
a row of small beads, may form; and finally there is a distinct, irregular, 
and wart-like fibrinous elevation (Fig. 203). To cases of this character 
the name verrucose endocarditis (Fig. 204) has been given; or, from the 
usually benign character, the name simple endocarditis; or, from its 
most frequent cause, rheumatic endocarditis. In other cases the mass of 
fibrinous deposit is more abundant and more irregular, while in still others 
the deposit of fibrin does not take place, or, if so, is soon detached, while 
necrotic changes occur in the endocardium, leading to the formation of 
irregular ulcers. Secondary deposits of fibrin may cover an ulcer after its 
formation, or its edges may be heaped with fibrin; and not rarely the 




492 



A TEXT-BOOK OF PATHOLOGY 



active necrotic process in the endocardium is not visible until the fibrin- 
ous coating, which is usually considerable in such cases, is removed. 
These forms of endocarditis are those that have been termed malignant, 
diphtheritic, septic, mycotic, or ulcerative. They are especially frequent 
after puerperal sepsis or other septic diseases and in pneumonia, but 
there is no well-established dividing line between the benign cases and 
the severe cases, either in etiology, in morbid anatomy, or in the clinical 
course and termination, so that we prefer to regard them as varjdng 
grades of the ,same general process. 




Fig. 204. — Acute vegetative (verrucose) endocarditis. 



Microscopically, the endocardium beneath the coat of fibrin shows 
desquamation of the endothelial cells, with frequently some hyaline 
degeneration or coagulation necrosis. Below this there are round-cell 
infiltration and, as the process continues, proliferation of fibroblastic 
cells. The fibrinous covering of the valve itself consists of flakes or 
granular masses, or a fibrillar network. By the proper staining methods 
masses of bacteria may frequently be demonstrated in -the superficial 
layers of the endocardium, in the fibrinous deposit, and usually at the 
bases of the leaflets or in the muscle. 

The simple differs from the malignant forms of endocarditis merely 
in the lesser activity of the necrotic changes in the endothelium and 
the greater prominence of reparative processes (round-cell infiltration, 
proliferation of connective tissue). 

Associated with endocarditis will always be found some degree of 
myocarditis which is usually degenerative, but in the severe septic cases 
is infiltrative and necrotizing. Such myocarditides are almost always 
replaced by cicatrization, except in rheumatic myocarditis (q. v.). There 



DISEASES OF THE CIRCULATORY SYSTEM 



493 



are in addition usually some lesions in the coronary circulation arising 
by extension from the myocardial changes, as an embolic process from 
the valves or as a part of an acute generalized disease. The lesions take 
the form of thrombotic intimitis or degenerative sclerosis, processes 
that very easily can have an effect upon the muscles in long standing 
valvulitis. 

Results. — Simple endocarditis may be healed by the gradual ab- 
sorption or breaking off of the fibrinous deposit and its dissemination 
in the circulation, with coincident thickening of the endocardium at 
the point of disease by the formation of fibroblastic cells and sclerotic 
connective tissue. When the process is very limited, and especially 
when the mural endocardium is affected, merely a white spot of thick- 
ening on the endocardium results. When the process is deep there may 



Fig. 205. — Aneurysm of the mitral valve, with rupture of the valve-cusp, seen from 
the auricular surface: a, Wall of left auricle; b, anterior segment of the mitral valve, the 
chordae tendinese have been cut short; c, aneurysm with triangular opening (Bramwell). 

be decided distortion by contraction of the new-formed Connective 
tissue. When the deposit of fibrin is large it frequently undergoes cal- 
cification, and remains as an irregular, calcareous mass attached to the 
valve. In the severer or malignant cases destruction of an entire valve 
or of one of the chordae tendinese may occur. When one of the layers of 
the valve alone is penetrated acute valvular aneurysm may be formed 
by a pouching of the other layer of the valve (Fig. 205). 

Mural endocarditis of malignant type may lead to myocarditis 
of a purulent character, and may even penetrate to the pericardium and 
set up a purulent pericarditis. 

Lesions in Other Organs. — The most serious danger of endocarditis 
is embolism. Small fragments of the fibrinous deposits are liable to be 
carried off into the peripheral circulation, and in ulcerative cases frag- 
ments of the valves themselves may be so conveyed. They are prone 
to lodge in the arteries of the spleen, kidneys, and brain, forming hemor- 
rhagic infarcts or metastatic abscesses, according to the non-infective 
or infective character of the embolus. 



b. 




a 



494 



A TEXT-BOOK OF PATHOLOGY 



Subacute or chronic malignant or recurrent endocarditis is 

that form in which the pathological change in the valve is not of a rapidly- 
progressive nature, but is often sluggish or chronic in its pathological 
and clinical behavior. The term 'recurrent" has been used to indicate 
that cases of old valvular lesions are especially prone to this type of 
reinfection. There is commonly a bacteremia, the most common or- 
ganism found being a streptococcus similar to both the pyogenic strep- 
tococcus and the pneumococcus, called the Streptococcus viridans. We 
have discussed the nature of the infection under the general subject of 
remittent infections; the reason for the persistence of the organism in the 
body for so long a time will be found by consulting the text upon fixed or 
fast bacterial strains. The pathological lesions are those of low-grade 
vegetative endocarditis, affecting principally the mitral valve, but by no 
means confined to it, and assuming the form of flat gray or greenish 




Fig. 206. — Aneurysmal distention and rupture of aortic and mitral valves consequent upon 
ulcerative endocarditis. (From the Vienna General Hospital Collection.) 

excrescences which distort the valves very little until quite late. There is 
a moderate anemia associated with an irregular leucocytic count. The 
lymphatic and myeloid tissues are congested. Nephritis, of a focal 
hemorrhagic type from thromboses in the glomeruli, may arise. The 
termination may be gradual exhaustion, an acute exacerbation and death, 
or transition to a cicatrizing endocarditis. 

Chronic endocarditis usually affects the valves of the heart and 
leads to the distortion of the valves constituting chronic valvular heart 
disease. Clinically, there are signs of disturbances, and eventually 
more or less complete failure of the circulation. 

Etiology. — Chronic endocarditis may be merely the continuation 
of acute endocarditis, or it may occur as an insidious process, chronic 
from the outset. In the former group of cases the causes are, of course, 
those of acute endocarditis, and it is particularly the rheumatic form 



DISEASES OF THE CIRCULATORY SYSTEM 



495 



that is likely to pass on to a chronic condition. The severer grades of 
acute endocarditis, or those commonly spoken of as malignant endo- 
carditis, are usually fatal, though occasionally they may terminate by 
reparative overgrowth of fibrous tissue. The group of cases in which 
the disease is chronic from the start has much in common with arterio- 
sclerosis and atheroma, as far as etiology is concerned. They may be 
toxic in their origin. These cases occur more frequently in persons of 
advanced years and in those whose occupation has been laborious. 
Chronic alcoholism, gout, lead-poisoning, syphilis, and diabetes are 
among the recognized causes. Not rarely the endocardial disease is 
secondary to the arteriosclerosis, and it may be directly due to it, re- 
sulting from the constant elevation of blood-pressure due to that disease. 
Laborious occupations act in a similar manner. The aortic valve may be 
involved by an extension downward of a syphilitic aortitis. 

Pathological Anatomy. — The changes that occur in the endocardium 
are overgrowth of fibrous tissue, causing thickening with subsequent 
contraction and distortion of the valves. The chordae tendinese are fre- 
quently involved and become converted into sclerotic cords of a whitish 
color, and less frequently white elevations are seen upon the mural 
endocardium. 

Microscopically, there are found the characteristic appearances 
of new-formed connective tissue, with occasionally, in the earlier states, 
the appearances of granulation tissue. New-formed blood-vessels may 
be found within this tissue, though frequently these are degenerated 
(hyaline and obliterated). Subsequently other degenerations take 
place. The area of thickening becomes more translucent and hyaline, 
then opaque and soft; coagulation necrosis and fatty degeneration take 
place, and there may thus be formed beneath the endocardial surface a 
lesion somewhat resembling a minute abscess. This may rupture upon 
the endocardial surface, forming a so-called atheromatous ulcer, upon 
which fibrinous deposits may collect; or it may be slowly inspissated 
and converted into a calcareous patch. In cases in which acute endo- 
carditis with thrombotic deposits passes into chronic endocarditis the 
fibrinous masses of the surface may be rendered calcareous at the same 
time that the sclerotic processes are taking place in the valve. Sub- 
sequently the same degenerative changes and calcification may occur 
in the tissue of the valve itself as are seen in the atheromatous form 
of the disease. In the late stages it is often quite impossible to deter- 
mine whether the case began as an acute endocarditis, or whether it was 
chronic from the first. 

The segments of the valves are frequently greatly shortened and 
rounded, so that they become mere stumps, or they may be curled 
upon themselves or drawn back and firmly adherent to the wall of the 
aorta, pulmonary artery, or the ventricular cavity. The individual 
segments may be agglutinated and united as a ring or diaphragm pro- 
jecting from the valvular insertion. 

The valvular function is interfered with in two ways: first, obstruc- 
tion may be offered to the outflow of blood by the rigid projecting valves 
and contracted orifice, a condition to which the term stenosis is applied; 
or, on the other hand, the valves may be so distorted, shortened, or 



496 



A TEXT-BOOK OF PATHOLOGY 



drawn backward that they are no longer able to close, and insufficiency 
results. The semilunar valves are particularly prone to be shortened, 
thickened, and recurved, and insufficiency is, therefore, most likely to 
occur. The mitral valve is frequently thickened and converted into a 
funnel-like formation by agglutination of the edges of the anterior with 
those of the posterior segment. There may thus be merely a slit-like 




Fig. 207. — Aortic obstruction from above. The margins of the leaflets are fused to- 
gether, thickened and calcified, reducing the orifice to about one- third of its normal caliber. 
The mitral and tricuspid orifices are also sclerosed and contracted. (Norris-Landis.) 

orifice (button-hole mitral), which occasions great obstruction to the 
outflow of blood from the auricle. Somewhat similar changes are met 
with at the tricuspid valve. The pulmonary valve is rarely affected 
in later life, but is sometimes the seat of fetal endocarditis, leading to 
permanent changes. 

Resulting Changes in the Heart. — The valvular defects can be 
overcome in only one way — by increase of the power of the heart muscle. 
Hypertrophy is, therefore, the natural result. This affects first the 



DISEASES OF THE CIRCULATORY SYSTEM 



497 



cavity upon which excessive work falls as the result of the regurgitation 
of blood in cases of insufficiency, or as the result of the excessive strain 
placed upon the heart wall to force the blood through the narrowed 
orifice in stenosis. The amount of hypertrophy varies with the condition 
of the general health of the individual and with the seriousness of the 
heart lesion itself. When the general health is good there is apt to be 
commensurately adequate hypertrophy, and when the lesion is not of 
sufficient gravity to interfere with the circulation in the coronary arteries, 
and the heart is, therefore, constantly supplied with a sufficiency of 
blood, hypertrophy is well maintined. Eventually, as the result of 
continued overwork and of continuously increasing embarrassment of the 
circulation or of intercurrent diseases, the heart muscle suffers fatty or 
fibroid degeneration, the cavities dilate, and the circulation fails. 

Changes in Other Organs. — The passive congestions resulting from 
failure of the muscle of the heart are often extreme, and may lead to 
profound changes -in various organs, notably the lungs, liver, and kidneys. 
These are discussed in the appropriate sections. Embolism is a not 
infrequent accident in chronic endocarditis, the emboli being parts of the 
valvular deposits or parts of thrombi in the cavities of the heart. 

Pathological Physiology. — -Endocarditis, acute and chronic, leads to 
various disturbances of the circulation and of the general health. In 
acute endocarditis the lesions may become the center of dissemination 
of infectious material, and the disease may run its course with all the 
manifestations of an obscure septicemia. This is particularly true of the 
cases usually designated as malignant. Serious disturbance of the 
hear^ action occurring in acute cases is sometmes difficult to explain. 
The lesions upon the valves may be seemingly very insignificant, and 
yet the heart may be very irregular in action and exceedingly weak. 
In part this may be reflex and in part it is probably the result of asso- 
ciated disease of the myocardium. Some investigations, made according 
to modern methods, have shown the heart muscle implicated more often 
than has been suspected. Acute myocarditis and diseases of the blood- 
vessels of the myocardium (thrombosis) have been discovered. 

Chronic endocarditis (valvular disease) occasions more or less pro- 
found mechanical disorders of the circulation. The severity of these 
depend upon the condition of the heart muscle more than upon the 
severity of the valvular lesion. There is always a tendency to com- 
pensatory hypertrophy of the heart muscle, and for a time this may 
suffice to avert serious disturbances; but with hypertrophy there is 
always some degenerative change (fibrous myocarditis and, later, fatty 
degeneration), as a result of which the cardiac power eventually fails, and 
symptoms of venous congestion develop. The degree of hypertrophy 
and of degeneration depends upon the nature and severity of the val- 
vular lesion, upon the age and general condition of the individual, and 
upon associated local conditions, such as disease of the coronary artery. 

It might be well, before discussing the efiect of decompensation, to 
review briefly normal heart action and the results of valvular defects 
upon it. Normal filling of the arterial circuit requires the harmonious 
action of valvular stops with muscular dilatation and contraction, a system 
be ginning for example in the left auricle, passing through the left ventricle 

32 . 



498 



A TEXT-BOOK OF PATHOLOGY 



to the aorta, returning via the cavae to the right auricle and ventricle 
whence it is continued into the pulmonary circulating to complete the 
round at the left auricle. At each station of this system, there are peri- 
odic halts in the current under the control of the heart beat and with 
each halt one part must empty itself as another fills. This requires of 
course no defect, first of the valves of the pump and the ability of the 
forcing power to empty spaces that are filled. We have learned that with 
inflammatory changes masses may form upon the surfaces of valves and 
that when valves are ulcerated away or distorted, by fibrous tissue they 
are unable to close properly. The first lesion will obstruct the onrush of 
blood while the latter will prevent the valve from supporting a column of 
blood when it tries to close. Since there is usually a myocarditis with 
valvulitis, involvement of valve bases by such a lesion will increase the 
deficiencies of the leaflets by failure of support at their bases. The 
effect of stenosis and regurgitation upon various chambers of the heart 
is as follows. If the mitral valve be stenotic, less than the required blood 
will pass into the ventricle and to the circulation; the ventricle shrinks 
or may hypertrophy. The auricle on the other hand enlarges to ac- 
commodate the blood received from the lungs and may become dilated; 
eventually the lungs become congested and throw extra work upon the 
right ventricle which may become hypertrophic. Insufficiency of the 
mitral valve valve has essentially the same effect, except that the left 
ventricle works to supply enough blood to the systemic circulation and 
at the same time against the pressure of the blood in the auricle, a force 
felt through the incompletely closed mitral valve. Aortic stenoses puts 
considerable extra work upon the left ventricle at once so that hyper- 
trophy begins early. Should this fail, dilatation would result, bringing 
with it insufficiency of the mitral, the overfilling of the lungs and pressure 
upon the right heart. Insufficiency of the aortic valve will have the same 
effect as the last except that by leakage back from the aorta so much 
room is occupied that normal diastolic filling of the left ventricle, through 
the mitral, cannot occur and there is early an overfilling of the auricle. 
This is compensated for by hypertrophy and dilatation of the left ven- 
tricle, usually very successfully. Pulmonary valvulitis, a rare condition, 
will always throw extra work at once on the right ventricle because it is 
from this chamber that the lungs are supplied ; tricuspid disease will have 
the same effect. The wall of this chamber must increase in work capacity 
to overcome either obstruction by stenosis of the pulmonary or insuf- 
ficiency of the tricuspid while in pulmonary insufficiency it has no chance 
to allow the right auricle to fill it since blood will leak back from the 
pulmonary artery during diastole. Primary right sided lesions are 
however rare, hypertrophies and dilatations usually being secondary to 
left sided valvulitis; multiple lesions do, of course, occur. All these 
impediments are cared for by the inherent power of hypertrophy in the 
heart muscle. What actually causes this is not certainly known but it is 
usually believed to be simply a response to a demand for more work. 
What causes the failure of hypertrophy is also not certainly known but 
we feel that if there be a single factor at the basis of successful hyper- 
trophy it is a sound myocardium supplied by good coronary arteries. 
However, these two things probably never exist in a chronic valvulitis. 



DISEASES OF THE CIRCULATORY SYSTEM 



499 



It is usually some severe strain which turns a hypertrophy into a dilatation 
but many cases occur without definite history. 

When compensation fails the various organs of the body suffer con- 
gestion. The lungs are first affected in disease of the left heart (mitral 
and aortic disease). The capillaries of the pulmonary alveoli become 
overfull, and encroach upon the lumen of the alveoli, or by elongation 
stretch the alveolar walls and render them inelastic. In either case 
proper respiration is prevented — a condition which is further aided by 
the retarded pulmonary circulation. As a result of these conditions, 
dyspnea (cardiac asthma), cough, and expectoration develop. In ex- 
treme cases edematous exudation takes place, and in long-continued 
cases cyanotic induration of the lung occurs. In such instances there 
may be continuous cough and respiratory insufficiency. 

When the right heart fails, the liver, spleen, gastro-intestinal mucosa, 
the kidneys, and the peripheral circulation suffer congestion. The liver 
may become greatly engorged, and in certain cases (tricuspid regurgita- 
tion) actually pulsates with each ventricular systole. The swollen liver 
cells and the engorged vessels cause obstruction of the biliary capil- 
laries, and consequently produce jaundice. To some extent this may be 
due to associated congestion of the biliary channels. Congestion of the 
gastro-intestinal mucosa may occasion various forms of gastric or in- 
testinal derangement. 

Metabolic disturbances of various sorts may occur in consequence 
of the imperfect circulation. The respiratory exchange of gases, in some 
cases at least, is reduced, though the degree of cyanosis cannot be taken 
as an index of the reduced oxidation. In man peripheral cyanosis is de- 
pendent upon stagnation of circulation and reduced oxidation. The 
products of metabolism excreted in the urine may indicate the reduc- 
tion in oxygen in the tissues. The metabolic consumption of the pro- 
teins of the body seems to be increased, but the explanation of this fact 
has not yet been satisfactorily determined. Some regard it as a con- 
sequence of molecular necrosis due to insufficiency of the supply of oxy- 
gen. The excretion of nitrogenous elements may, however, be reduced 
when transudates are forming. This is due to the storing up of meta- 
bolic products in the transudates. The urine may present albumin as a 
result of chronic congestion and secondary renal disease; the hepatic 
functions are disturbed by congestion and jaundice may result; and in 
the more severe instances hydrobilinuria occurs. The condition of the 
blood is of special interest. During periods of failing compensation the 
concentration of the blood is increased or normal, and the number of 
blood-corpuscles may be excessive. In part, at least, these conditions 
are explained by the assumption that the corpuscles are retained in 
the peripheral parts of the circulation in greater measure than the fluid 
elements (see Polycythemia). When the cardiac compensation is well 
maintained some anemia may be apparent, especially in cases of aortic 
disease. 

Disturbance of the rate or rhythm of the heart is not infrequent. 
The rate is usually more rapid, but in aortic stenosis it may be slow. 
This is in effect a conservative process, as it enables the ventricle to dis- 
charge its contents through the narrowed orifice. Arrhythmia is gener- 



500 



A TEXT-BOOK OF PATHOLOGY 



ally proportioned to the grade of degeneration of the muscle of the heart 
and is especially marked in cases in which the walls of the auricles are 
involved. The attempt to connect disorders of rhythm with disease of 
the intracardiac nervous mechanism has thus far failed of demonstration. 
On the other hand, the relation of myocardial disease to arrhythmias 
has become increasingly evident. Increased irritability of the heart 
muscle in certain stages of myocardial disease readily explains some of the 
cases of extrasystolic irregularity. Lesions of the bundle of His may 
occasion partial or complete dissociation of the auricular and ventricular 
contractions (partial or complete "heart-block''). Various other types 
of arrhythmia may also be explained by myocardial disease. 

Myocardium 
circulatory disturbances 

Anemia of the heart muscle may be part of a general anemia. It 
may occur in cases of narrowing or obstruction of the coronary arteries, 
and it may be the result of the pressure of pericardial e usions. When 
long continued it leads to fatty degeneration of the heart, but is itself 
of little consequence. 

Hyperemia of the heart muscle may occur when there is obstruction 
to the return of the blood to the right heart through its venous channels. 
It may be part of a general hyperemia in a failing compensation of valvu- 
lar or muscular diseases of the heart. The heart muscle assumes a dark- 
red color, and the veins are seen under the epicardium as dilated bluish 
vessels. 

Hemorrhages in the heart muscle may result from obstruction of the 
coronary arteries, when the hemorrhage assumes the form of an infarct. 
There may also be hemorrhages in cases of intense myocarditis or sur- 
rounding abscesses of the heart muscle, and finally points or streaks of 
hemorrhagic infiltration may be seen between the muscle-fibers in per- 
sons who have died from some form of hemorrhagic diathesis, from 
sepsis, or from various intoxicants. 

DEGENERATIONS 

Parenchymatous degeneration, or cloudy swelling of the heart, 
was designated by Virchow as parenchymatous myocarditis. It is es- 
sentially a degenerative process and should be so described, though it 
forms a not inconsiderable part of the pathological changes occurring in 
the heart in acute myocarditis. 

Etiology. — The immediate cause is infection. It is met with in the 
course of diphtheria, typhoid fever, scarlet fever, rheumatism, and 
other infections. It may be that elevation of the temperature alone 
suffices to bring it about, and in these cases no doubt abnormal sub- 
stances resulting from disordered metabolism are the direct toxic agents, 
but, as a rule, it is the specific toxin of the infections that occasions the 
myocardial disease. Localized parenchymatous degeneration may be 
found in the heart-fibers adjacent to areas of endocarditis or pericarditis, 
and doubtless the same etiological factors are at work in this as in more 
generalized instances. 



DISEASES OF THE CIRCULATORY SYSTEM 



501 



Pathological Anatomy. — The changes are more marked in the left 
ventricle than elsewhere, though any part of the heart may be affected. 
As a rule, parenchymatous degeneration occurs as a diffuse process, but 
there may be only limited areas here and there. The myocardium be- 
comes pale in color; it is softer than normal, the heart walls are usually 
flabby, and the cavities somewhat dilated. Microscopically, the fibers 
are found to be filled with fine granules of albuminoid nature, which 
may completely obscure the striations and even the nuclei, but which 
may be cleared up by the addition of acetic acid. Multiplication of the 
nuclei and round-cell infiltration of the intermuscular connective tissue 
may be observed, but these are inflammatory changes rather than de- 
generative, and are not, therefore, strictly a part of the disease in question. 
Parenchymatous degeneration may be complicated by a form of hyaline 
degeneration, the affected fibers becoming converted into cylinders of 
waxy appearance. When cloudy swelling persists, fatty degeneration is 
usually the terminal change. 

Amyloid infiltration results from the causes which incude amyloid 
disease in other organs. It is not infrequently found in minute areas 
here and there, but only rarely has it been seen as a widespread process 
affecting the connective tissue between the muscle-fibers and beneath 
the endocardium and pericardium. In such cases the same wax-like 
appearance is seen as in the liver or spleen, and the characteristic reac- 
tion with iodin may be demonstrated. 

Hyaline degeneration is sometimes associated with amyloid, and 
gives rise to a glassy or waxy transformation of the connective tissue. 
It is usually seen in small areas, but may be quite widespread. Zenker 
described a form of hyaline disease (vitreous degeneration) of the muscle- 
fibers themselves as occurring in typhoid and other infectious fevers, and 
affecting the heart muscle as well as the muscles of the abdominal wall. 
This is usually associated with parenchymatous degeneration and occurs 
in limited areas. Microscopically, there may be seen small hyaline 
masses or globular areas embedded in the muscle-fiber, the rest of the 
fiber showing the appearances of cloudy swelling. 

Fatty infiltration, or obesitas cordis, is but an increase of the 
normal condition. In the normal heart there is a certain amount of fatty 
deposit beneath the epicardium, especially in the furrows and along the 
lines of the blood-vessels. In disease this may become enormously 
increased and there may be penetration of the adipose tissue into the 
wall of the heart between the muscle-fibers, sometimes as far as the sub- 
endocardial fibrous layer. 

Etiology. — The causes are those which induce general obesity. Thus, 
it may be the consequence of a hereditary tendency or sedentary habits, 
with overeating and drinking ; it is more common in advanced years than 
in early life. Very frequently it is met with in women who have grown 
• ■ stout at the menopause; sometimes, however, considerable deposit about 
the heart may occur in persons otherwise presenting no tendency to 
fatness. 

Pathological Anatomy. — The adipose tissue beneath the visceral peri- 
cardium may be slightly increased in amount, or the heart may be em- 
bedded within an enormous deposit of fat, which may involve not alone 



502 



A TEXT-BOOK OF PATHOLOGY 



the epicardium, but the parietal layer and the mediastinum as well. 
On section through the heart" wall, trabecule of adipose tissue may be 
seen passing through the heart's substance, and sometimes deposits may 
be seen as a uniform infiltration beneath the endocardium, or as localized 
deposits projecting into the heart cavity. Microscopically, fatty infiltra- 
tion presents the ordinary appearances of adipose cells lying between the 
heart muscle-fibers (Fig. 208). The muscle-fibers themselves are not 
involved; but may become atrophic from pressure, and in such instances 
present a more yellowish or brownish color than normal, and micro- 
scopically show an abundance of granules. In other cases pronounced 
fatty degeneration is seen in the muscle-fibers. 




Fig. 208. — Fatty infiltration of the heart, from a section through the wall of the right 

auricle (Bramwell). 

Results. — Weakening of the heart muscle must necessarily result 
from the mechanical impediment imposed upon it. Circulatory dis- 
turbances are, therefore, met with, as in valvular disease or fatty de- 
generation. Occasionally rupture of the heart occurs, due to the 
atrophic condition of the muscle proper and a want of resisting power 
of the infiltrating adipose tissue. It is especially prone to occur when 
the disease is localized. 

Fatty degeneration affects the muscle-fibers themselves. 

Etiology. — Fatty degeneration results from malnutrition or from 
toxic agencies. The most frequent cause is anemia, either local or 
general. Local anemia is due to sclerosis and narrowing of the coronary 
arteries; or it may be the consequence of improper circulation in the 
coronary vessels attending the final stages of valvular disease of the 
heart. Fattj r degeneration is, therefore, a terminal condition in arterial 
sclerosis affecting the coronary vessels and in valvular disease. The 
remote or antecedent causes are those which bring about arteriosclerosis. 
We find it, therefore, in elderly persons of the male sex who have had 
syphilis, who have used alcohol excessively, or have gout or chronic 
Blight's disease. The fatty degeneration of the heart resulting from 
general anemia is most typically seen in pernicious anemia, in which the 



DISEASES OF THE CIRCULATORY SYSTEM 



503 



most extreme grades of fatty disease are sometimes witnessed. Of the 
cases which are due to toxic agents, we may distinguish those resulting 
from specific infections and those occurring in various chemical intoxica- 
tions. ' In the specific fevers, in which intense parenchymatous de- 
generation occurs, and among these diphtheria is most prominent, fatty 
degeneration is sometimes the terminal condition. Among the external 
poisons capable of producing the disease phosphorus and arsenic are 
important. 

Pathological Anatomy.— Fatty degeneration may be localized or a 
diffuse process. As a rule, a considerable portion of the heart is affected, 
but only isolated fibers or groups of fibers are involved. There results 
a somewhat speckled or mottled condition (titration), which is especi- 




Fig. 209. — Fatty degeneration of the heart muscle, stained by the osmic acid method, 
showing granular character of change. Some of the fibers retain a little cross striation 
and the granules may be so arranged. 

ally visible beneath the endocardium. Streaks or lines of a yellowish 
or whitish color alternate with the darker portions of normal muscle. 
When the process is uniform the entire muscle assumes a yellowish hue. 
It is softer than normal, the cavities tend to dilate, and the walls may be 
considerably thinner than normal. 

Microscopically, the muscle-fibers are found to be filled with small 
granules of a dark color or with small droplets of high refractive power 
(Fig. 209). These may completely obscure the nucleus, or they may be 
arranged in groups at the poles of the nucleus. Sometimes distinct 
vacuolization of the fibers is seen, especially in cases in which fibroid 



504 



A TEXT-BOOK OF PATHOLOGY 



myocarditis accompanies the fatty change. The nature of the granules 
and droplets within the fibers is well demonstrated by treating the 
section with osmic acid, when the fat-droplets become intensely black. 

Associated Conditions. — In cases of coronary sclerosis, or valvular 
heart disease with failure of compensation, fatty degeneration is rarely 
the sole pathological condition. As a rule, fibroid myocarditis accom- 
panies it, and the latter may be the more extensive and important condi- 
tion of the two. Fatty infiltration is often met with as an associated 
condition, and may be the direct cause of the degeneration by the pres- 
sure exerted upon heart muscle-fibers by the infiltrating fat. Rupture 
of the heart may occur in cases in which fatty degeneration affects local- 
ized areas, as is often the case near the apex of the heart. 

Segmentation of the Fibers. — This is an interesting condition 
occasionally observed, especially in cases in which sudden death has 
taken place. It consists in a transverse splitting of the fibers, by which 




Fig. 210. — Marked general segmentation with great diastasis of the pieces; X 120 (from 
the American Journal of the Medical Sciences) (Hektoen). 

they are converted into columns of varying length separated by trans- 
verse fissures (Fig. 210). It has been described under the name of 
etat segmentaire or myocardite segmentaire by French writers. A con- 
siderable discussion as to its significance has arisen, some holding that 
it is a condition of clinical as well as of pathological importance; others, 
that it occurs during the death-agony or postmortem. Whether the 
latter statement be true or not, the segmentation seems to indicate an 
abnormal fragility of the fibers and in particular of the cement-substance, 
though it may not be demonstrable by our present means of examination. 
Some observers maintain that it occurs when there has been excessive 
dilatation of the heart just antemortem. This fragility may be due 
to digestive action of bacteria or bacterial products, as has been sug- 
gested. Some investigations seem to indicate that segmentation is 
purely artificial, and brought about by the imperfect adjustment of the 
knife in cutting. 



DISEASES OF THE CIRCULATORY SYSTEM 



505 



Degeneration of the intracardiac ganglia has been noted by a 
number of observers in myocarditis and in cases of angina pectoris with- 
out gross cardiac alteration. The changes observed are swelling or 
granular, fatty and hyaline degeneration of the ganglion-cells, and in- 
filtration with round cells and sclerotic formation between the nerve-cells. 
The importance of these changes has not been determined. 

Pathological Physiology. — The functional disorders in degenera- 
tions of the myocardium may be due to the direct injury of the fibers, or 
to disturbances of the nervous mechanism of the heart. The latter seems 
to be the case in instances in which marked cardiac irregularity, or 
arrhythmia, occurs. The disease of the fibers explains the weakness of 
the heart's action; and this is especially marked in cases of fatty and 
fibroid disease in which the circulation through the coronary arteries is 
insufficient. Recent investigations have shown that fatty degeneration 
of the heart muscle in itself causes much less cardiac weakness than has 
generally been supposed. Sometimes the heart is arrested and sudden 
death occurs in cases of myocardial degeneration due to infectious fevers 
(diphtheria). This was formerly ascribed to heart-clots, but is now 
recognized as a form of sudden and complete asystole due to the myo- 
cardial disease or to associated nervous disorders, organic (in the intra- 
cardiac ganglia or in the cardiac nerves) or reflex. The disturbances of 
the general circulation in myocardial disease and their results are similar 
to those met with in valvular disease. (See also Pathological Physiology 
of Fibroid Degeneration of the Heart.) 

Physiological investigations of the mechanism of cardiac activity 
have during the last ten or fifteen years brought to light the existence of 
a special system of fibers composed of somewhat undifferentiated muscle 
cells which appear to be all important as the seat of stimulus production 
and as the pathways for the conduction of stimuli from their place of 
origin to the muscle groups of the auricle and ventricle. This system 
begins in a swollen portion known as the Keith-Flack node, situated at 
the junction of the superior vena cava and right auricle. From this 
node the fibers extend downward through the wall of the auricle, spread- 
ing out under the endocardium and become contracted again to a narrow 
band or bundle, the atrio-ventriculo-bundle of His, at the upper portion 
of which (that is in the lower part of the right auricle) is found another 
nodal swelling generally called the node of Tawara. The atrio-ventriculo- 
bundle after it has passed through the junction between the auricle 
and ventricle divides into two branches, a right and a left, supplying 
the respective ventricles and terminating in a complex of fine fibers 
which are ultimately distributed to the muscle of the ventricles. 

Normally stimulus production originates in the Keith-Flack node 
which has, therefore, been called the pacemaker oj the heart From it 
stimuli flow down to the auricles then through the bundle to the 
ventricles. 

Derangements due to inherent diseased conditions or to influences 
from the outside through the extrinsic nervous mechanism of the heart 
may occasion increased or decreased rapidity of the stimulus production 
in the pacemaker or irregularities in the intervals between the stimuli 
(sinus arrhythmia). Should the pacemaker be sluggish in action or 



506 



A TEXT-BOOK OF PATHOLOGY 



should there be some spot or spots of increased irritability in the wall 
of the auricle, ectopic stimuli may be produced at such spots, either 
occasionally (producing auricular extrasystoles) or constantly over 
considerable periods of time (auricular tachycardia). Sometimes the 
function of the pacemaker is taken up by the node of Tawara and doubt- 
less in consequence of functional or organic difficulties in the former. 

Disease or functional depression of the conductive mechanism 
especially in the bundle or in one of its main branches may occasion 
interruption in the conduction of impulses from the auricles to ven- 
tricles. This interruption may occur occasionally, causing missed beats 
or with regular recurrence when the rate of auricular contractions may 
be two or three times as frequent as the ventricular contractions (partial 
heart block). Finally complete interruption of conduction causes com- 
plete dissociation of auricles and ventricles. The former contract at 
their usual or generally somewhat accelerated rate, while the ventricles 
contract with more or less regularity by reason of their inherent power 
of rhythmic contraction (iodio-ventricular rate) . Usually this rate is about 
30 per minute. Cases of complete heart block are frequently attended with 
attacks or paroxysms of syncope, spasms or even convulsions, the whole 
clinical complex being known as Stokes- A dams' syndrome. 

In cases of chronic cardiac disease and sometimes in acute infectious 
or toxic conditions, normal contractions of the auricles fail and in place 
of these there occurs a fibrillation of the auricular walls resembling the 
fibrillation of degenerating or dying muscle. These fibrillations are re- 
cognizable as minute waves in electro-cardiographic tracings or less 
satisfactorily in polygraphic records. Under these circumstances stimuli 
corresponding to the separate innumerable auricular fibrillations traverse 
the conducting mechanism; many of them doubtless fail to reach the 
ventricle and of those that do reach the ventricle, only a portion succeed 
in provoking ventricular response, as a definite rest time is necessary 
before a ventricle will contract after a previous contraction. The 
ventricular contractions are extremely unequal in frequency and strength, 
a condition to which the clinical term total arrhythmia is applied. 

A frequent form of cardiac arrhythmia and one not necessarily of 
serious consequence is that in which owing to an irritable portion of 
the ventricle, ectopic contractions are originated at such spots, bringing 
about so-called ventricular extrasystoles. 

Other clinical forms of cardiac irregularity or arrythmia may be 
due to alterations in the contractile power of the ventricles or in their 
capacity of excitability by reason of which either the strength of con- 
tractions or their regularity may be altered. 

INFLAMMATION 

Inflammation of the heart muscle, or myocarditis, may be either 
acute or chronic, diffuse or circumscribed. 

Acute myocarditis was designated "carditis" by the older writers, 
though the same term was applied to endocardial and pericardial in- 
flammations as well. It may be circumscribed or diffuse, the former 
appearing most frequently in the form of abscesses of the heart muscle. 



DISEASES OF THE CIRCULATORY SYSTEM 



507 



Acute circumscribed myocarditis, or abscess of the heart may 
occur in connection with penetrating endocardial lesions or in association 
with pericarditis. More frequently the infection takes place through 
the coronary circulation, and the metastatic abscesses of the heart are 
but a part of a general pyemic disease (Fig. 211) such as occurs in puer- 
peral sepsis, in osteomyelitis, and other intensely septic diseases, but 
particularly in malignant endocarditis. 



Pathological Anatomy. — When the infectious emboli are large, a 
single abscess or a few abscesses result, while in cases of finely dis- 
seminated infectious particles the heart substance may be studded with 
innumerable suppurating points. These are more common in the left 
ventricle and in the anterior wall than elsewhere. At first the lesion 
may present itself as a minute, hemorrhagic, or necrotic area, but soon 
the focus softens and forms a purulent collection. In size the abscesses 
vary from the merest points to cavities the size of a cherry, and as much 
as an ounce of pus has been removed from a single cavity. Perforation 
may take place into the heart itself, and acute cardiac aneurysm or even 
rupture of the heart may ensue. On the other hand, the abscess may 
discharge into the pericardial sac, or without such rupture may set up 
purulent pericarditis. Occasionally the pus becomes inspissated and 
fibrous overgrowth causes its complete encapsulation, or finally, the 
area may be rendered calcareous. Such terminations, however, are 
rare, the patient usually perishing of the pyemic process, as a part of 
which the abscesses in the heart occur. 

In suppurative myocarditis occurring from extension in consequence 
of malignant endocarditis communicating sinuses may be established 
between the chambers of the heart. 

A non-suppurating form of interstitial myocarditis may occur, and 
Aschoff has called attention to such a process in rheumatic conditions 
associated with endocarditis. A similar lesion has been found in the 
heart in chorea. There is a leukocytic and mononuclear infiltrate some- 
times in nodular form, following the blood-vessels. The peculiarity 




Fig. 211. — Embolic abscess of the myocardium. 



508 



A TEXT-BOOK OF PATHOLOGY 



of these lesions lies in the large cells with large single or multiple nuclei 
and their rather circular arrangement. By some they are looked upon 
as wandering cells, by others as local cells become hypertrophic. There 
may be a small amount of fibrin. This lesion occurs most commonly in 
the left ventricular wall. It may be removed without leaving a trace, 
or a small fibrotic patch may remain. These bodies are not producible 
in experimental animals by injection of the cocci which can cause en- 
docarditis and are said to cause rheumatism. 

Acute diffuse myocarditis occurs in various forms of infectious 
fevers. It was first recognized in typhoid fever, but is more common 
in diphtheria and scarlet fever, and is met with in acute rheumatism, 
puerperal septicemia, and various other infections. It is most likely 
that the toxins of the infectious diseases named are the immediate 
causes, and not the specific bacteria themselves. The process may be 
entirely diffuse, but in most cases the left ventricle is more seriously in- 
volved than other parts, and often there are merely localized areas of 
myocarditis scattered about in various parts of the ventricular wall. 

Pathological Anatomy. — The affected heart muscle is soft and often 
distinctly friable. In the earlier stages there may be spots of hemor- 
rhagic infiltration, but, as a rule, the 
• ' color is rather lighter than that of 

■ the normal organ. It may be notice- 
• able that the bundles of fibers easily 
J ^.v-* iff separate from one another. The 
cavities of the heart are frequently 
'Jfi dilated, particularly the left ventricle. 
l^^f^'^f^^^^^^^i^ Microscopically, the important 
K'fijffi&Ze f*fZ chan S es are diffuse infiltration of 

BM ^ i * u * k ' A '-' 7 '■' ' round cells in the connective tissue 

Fig. 212.— Acute myocarditis, showing between the muscle-fibers (Fig. 212), 

degeneration of the muscle-fibers and , £ ,-i 

massive accumulation of leukocytes. and proliferation of the connective 

tissue itself, with formation of rounded 
or spindle-shaped fibroblastic cells. There is no tendency to sup- 
puration. The blood-vessels are usually somewhat distended with blood, 
and there may be distinct proliferative thickening of their walls. 
Degenerative changes of the muscle-fibers themselves are rarely, if ever, 
absent, and it is most probable that the first stage in the process is a toxic 
degeneration of the muscle-fibers, and that the intermuscular infiltration 
and proliferation are consequent upon the primary degeneration. The 
fibers become granular and opaque, the striations are indistinct; oc- 
casionally there may be vacuolization, and sometimes the segmenta- 
tion to which so much attention has been directed. Proliferation or 
swelling of the nuclei of the muscle-fibers is frequent, and the hyaline 
transformation of Zenker is sometimes observed. 

Results. — Under entirely favorable conditions acute, diffuse, and 
non-suppurative myocarditis usually terminates in complete resolu- 
tion. It is, however, quite likely that the proliferative changes noted 
in the intermuscular connective tissue often advance to complete or- 
ganization and formation of localized areas of sclerosis. Death from 
dilatation of the cavities and cardiac failure is not uncommon. 



DISEASES OF THE CIRCULATORY SYSTEM 



509 



Chronic myocarditis, or fibrous myocarditis, like the acute form, 
may be diffuse or localized, though in this case the circumscribed form is 
the more common. 

Etiology. — It is not unlikely that many cases are consequent upon 
acute diffuse myocarditis, as has been already suggested. In such cases 
the myocarditis may be looked upon as a primary affection. It may be 
a result of infection with Spirochceta pallida or various intoxications. 
More commonly the process is secondary, and is dependent upon pri- 
mary disease in, or disturbances in, the circulation of the coronary 
arteries. It is, therefore, very common to find areas of sclerosis in cases 
of atheroma of the coronary arteries or in valvular disease of the heart 
in which the coronary circulation has finally become deficient. In 
view of the foregoing and the fact that the condition is not accompanied 
by a continued inflammatory exudate, this condition takes a place with 
the reparative fibroses. The primary lesion is always degenerative. 
Among the remote antecedent causes are the conditions which are prone 
to occasion arteriosclerosis, such as old age, alcohol, gout, syphilis, and 
the like. The connection between the arterial disease and the resulting 
myocardial sclerosis has been the subject of considerable dispute. No 
doubt, in some instances, the circumscribed areas of fibrous overgrowth 
met with in the distribution of branches of the coronary artery repre- 
sent the scars of healed infarctions. In other cases, however, it would 
seem more likely that a slow degenerative change with gradual over- 
growth of the connective tissue occurs in consequence of the disturbed 
circulation through the damaged coronary vessels. Diffuse sclerosis may 
be associated with hypertrophy in cases of valvular disease and other 
conditions causing cardiac enlargement. Dehio has suggested that 
fibroid degeneration or myofibrosis is a conservative process designed 
to strengthen a heart wall that has become impaired by some degenera- 
tion or functional weakness, just as, according to Thoma, the fibrous 
nodules in arteriosclerosis serve to strengthen parts of the arterial wall 
that have become weakened by disease of the muscularis. 

Localized myocarditis with fibroid overgrowth is very commonly 
met with at the tips of the papillary muscles in association with chronic 
endocarditis and disease of the chordae tendinese. 

Superficial myocarditis of a fibroid character may be seen beneath 
the pericardium or endocardium which has been thickened by chronic 
inflammation. 

The association of fibroid myocarditis with uterine myofibromata 
is of some practical importance. 

Pathological Anatomy. — The characteristic change is the formation 
of sclerotic areas in the muscle substance. These appear either as more 
or less irrregular spots, or as streaks or lines running in the direction 
of the fibers of the heart. They are most common in the anterior 
wall of the left ventricle, near the apex, in the septum, and at the tips 
of the papillary muscles; but the entire substance of the heart may be 
involved and thickening of the walls may result. The impediment 
offered to the muscle of the heart by the intermuscular sclerosis may 
lead to true hypertrophy. Later, there is degeneration of the fibers in 
consequence of the pressure of the new-formed tissue, and yellowish 
areas of fatty degeneration are frequently observed. 



510 



A TEXT-BOOK OF PATHOLOGY 



Microscopically, the diseased areas are found to consist of more or 
less well-organized connective tissue lying between the muscle-fibers 
and pressing them far apart, or taking the place of atrophic muscle- 
fibers (Figs. 213 and 214). 




Fig. 213. — Edge of an area of fibrous myocarditis, showing replacement of the fibers by 

connective tissue (Orth). 

Sometimes certain portions show the earlier stages of the process, 
round-cell infiltration and proliferation of the connective tissue being 
the important features (Fig. 215). As. a rule, however, the diseased 
areas are found in a completely organized condition. The muscle- 
fibers themselves suffer granular and fatty degeneration, and not in- 
frequently distinct vacuolization is observed. 




Fig. 214. — Chronic myocarditis, showing extensive destruction of fibers. 

Results. — In cases in which a considerable area of chronic myocarditis 
has developed, as is not uncommonly observed at the apex in conse- 
quence of thrombotic or embolic obstruction of the anterior coronary 
artery, an aneurysm of the heart may result from gradual stretching of 
the fibroid area. In cases in which the process is diffuse the heart muscle 



DISEASES OF THE CIRCULATORY SYSTEM 



511 



may at first undergo hypertrophy in consequence of the excessive labor 
imposed upon it, but eventually degeneration from pressure upon the 
fibers gains the ascendency, dilatation of the cavities ensues, and general 
failure of the circulation is the terminal result. 

It is not unusual to find difluse arteriosclerosis and fibroid disease 
of other organs associated with chronic myocarditis. In such cases the 
antecedent cause is the arterial disease, which, in turn, may be dependent 
upon some systemic disorder. 



Fig. 215. — Endomyocarditis, showing, a, thickened endocardium; b, bands of muscle- 
fibers with interstitial infiltration of round cells and proliferated connective tissue (Bram- 



Pathological Physiology. — The immediate effect of chronic myo- 
carditis or fibroid degeneration of the heart is a loss of power. By 
some it has been held that the fibroid tissue is designed as a support 
for the heart muscle weakened by other causes, such as degeneration 
of the muscle-fibers themselves, just as it has been claimed that nodules 
of arteriosclerosis are intended as support for areas of weakness of the 
muscular layers of the arterial walls. This theory is not generally 
accepted; but, on the other hand, it is certain that the presence of fibrous 
tissue weakens the heart so far as its proper function (contractility) 
is concerned. For a time hypertrophy of the muscular elements may 
counterbalance the functional weakness occasioned by the fibroid change, 
but eventually the muscle fails, and this failure is usually hastened by 
fatty degeneration and atrophy of the muscle-fibers, which changes, 
in turn, are doubtless occasioned by the fibrosis, especially that in- 
volving the walls of the small nutrient arteries. In the early stages, 
with adequate hypertrophy, symptoms may be wanting, though a 




well). 



512 



A TEXT-BOOK OF PATHOLOGY 



strong action of the heart and an increase in its size may be detected. 
Later, progressively increasing weakness of the circulation, and eventu- 
ally all the signs of cardiac failure develop, just as in advanced valvular 
disease. Irregularity of the heart's actions is much more pronounced 
than in valvular disease, and is particularly prominent when the walls 
of the auricles are especially involved. It has been ascribed to im- 
plication of the intracardiac mechanism, and in so far as physical changes 
in the atrio-ventricular bundle are concerned, this seems to be the case 
in certain instances of auriculo-ventricular incoordination, however, all 
the types of arrhythemia or other abnomal contraction phenomena have 
not been explained satisfactorily on an anatomical basis. For the present 
it can only be said that the irregularity of action results from the disease 
of the muscle and the consequent disturbance of its automatic contractility 
and other functions. 

Angina Pectoris. — In many cases of fibroid heart, paroxysms of- 
pain occur. These may be moderate in severity and without definite 
characters, or they may be severe and of a uniform kind. The latter 
constitute the condition called angina pectoris. This is especially 
marked and frequent in cases of fibroid heart associated with advanced 
sclerosis of the coronary arteries. The cause of the paroxysms is uncer- 
tain. The seizures may possibly be due to minute embolisms and throm- 
boses of branches of the coronary arteries, or to muscle cramp caused by 
cardiac strain under effort or excitement in cases in which the coronary 
disease prevents a sufficient supply of blood. The former explanation 
derives some support from the recognized painful seizures that attend 
arterial occlusion everywhere, and from the disseminated patches of 
sclerosis of the heart muscle in cases of fibroid heart with coronary dis- 
ease and a history of angina. These patches of sclerosis may have had 
their origin in such embolisms or thromboses as are postulated. The 
muscle-cramp theory has its best support in the analogy of anginal 
paroxysms with the symptoms of intermittent claudication of the legs 
in cases of generalized arteriosclerosis. Neither of these explanations, 
however, suffices for all cases. Changes in the intracardiac ganglia and 
in the fibers of different parts of the cardiac nervous mechanism have 
been described, but are of uncertain significance. 

HYPOPLASIA AND ATROPHY 

Hypoplasia of the heart is a congenital condition in which the 
heart is insufficiently developed and remains undersized throughout 
life. This condition is frequently associated with hypoplasia of the 
aorta and other large vessels, and sometimes with a similar condition 
of the generative organs. Persons presenting status lymphaticus 
and women who develop chlorosis not rarely present the conditions 
referred to. These individuals are often of delicate structure, with 
feeble or unstable circulation, and, in the case of males, of effeminate 
nature and appearance. The heart is small in size and, as a rule, uni- 
formly affected in all parts. The epicardium may be somewhat wrinkled, 
and this condition, no doubt, has often led to the description of cases 
of this sort as instances of atrophy. Many cases of supposed hypoplasia 



DISEASES OF THE CIRCULATORY SYSTEM 



513 



are doubtless instances of true atrophy, the size of the heart being 
strictly proportioned to the emaciated body. 

Atrophy of the heart is usually described as occurring in two varie- 
ties, simple and brown atrophy. It is very doubtful, however, if simple 
atrophy ever occurs. Many of the cases so designated were doubtless 
hypoplasias, and other cases probably brown atrophies. 

Etiology. — Atrophy of the heart usually occurs in persons of ad- 
vanced age; but is occasionally met with in the young. It results from 
simple senility or from various cachectic or wasting diseases, such as 
tuberculosis, carcinoma, and the like. 

Pathological Anatomy.— The heart is small in size, sometimes weighing 
but a third or fourth of its normal weight. The capsule, or epicardium, 

is wrinkled, and may be somewhat thick- 
ened by fibrous tissue overgrowth or by 
fatty or mucoid change. The vessels 
are conspicuously tortuous (Fig. 216). 
The muscle is flabby and often quite 
dark in color. 

Microscopically, the fibers are found 
smaller than normal and contain excess 
of pigment. The latter is brownish or 






W- 






i. 


' 1 


4 \ ' 










% § m 


W 


u 


■I i 



Fig. 216. — Atrophy of the heart, seen 
from the front (two-thirds natural size) 
(Bramwell). 



Fig. 217. — Brown atrophy of the heart muscle 



black, and at first situated at the poles of the muscle nuclei (Fig. 217). 
Later the whole fiber may be uniformly pigmented. Sometimes the 
muscle-fiber is converted into a hollow sheath, containing scattered 
pigment granules and more or less fragmented nuclei. Complete de- 
struction of the fiber may lead to the apparent occurrence of pigment 
between the muscle-fibers. The pigment does not contain iron, and 
seems to be a derivative of the albuminous constituents of the fibers. 

Localized atrophy of the fibers may occur around areas of disease 
of the heart muscle, such as foci of myocarditis, tubercles, gummata, 
etc. The fibers present the same appearance as those just described. 

Pathological Physiology. — Atrophy of the heart muscle does not 
often occasion striking results or symptoms, as the process is in most 
cases commensurate with the general emaciation and decreased de- 
mand. Occasionally irregular action of the heart is noted, and sudden 
death has sometimes occurred. 

33 



514 



A TEXT-BOOK OF PATHOLOGY 



HYPERTROPHY AND DILATATION 

Hypertrophy and dilatation are usually associated and result from 
the same causes, the degree of hypertrophy or of dilatation present 
in a given case depending upon the suddenness of action or the intensity 
of the cause, and upon the state of the heart itself. A sudden strain may 
cause immediate dilatation; repeated strains of less severity cause 
hypertrophy in a well-nourished heart, or increasing dilatation in one 
the seat of myocardial weakness or degeneration. 

Etiology. — The influence of valvular diseases (q. v.) of the heart 
in developing hypertrophy has been sufficiently discussed. Various 
other causes may lead to overwork or cardiac strain, and occasion 
hypertrophy or dilatation. We may classify the causes in accordance 
with their operation upon either or upon both ventricles. 

Causes Acting on the Left Ventricle. — All forms of arterial disease, 
but especially diffuse arteriosclerosis, increase the work of the left 
ventricle notably, and may cause marked changes in it. Aneurysms 
of the aorta, however, have surprisingly little effect. Chronic Bright' s 
disease, especially the interstitial form, is a well-known cause. It prob- 
ably acts in several ways: partly by the associated arterial disease, 
partly by vascular contraction due to toxic products, and partly by the 
direct stimulation of cardiac action by the same substances. Excessive 
exercise or laborious occupation (mining, blacksmithing, etc.) may act 
upon the whole heart, but especially upon the left ventricle. 

Causes Acting on the Right Ventricle. — Diseases of the lungs and 
pleura, such as emphysema, fibriod phthisis, and pleural synechise, 
are frequent causes of hypertrophy and dilatation of the right ventricle. 

Causes Acting on the Heart as a Whole. — General functional over- 
stimulation may cause uniform enlargement of the organ. This may 
be seen in cases of hysteria, exophthalmic goiter, and other diseases in 
which the overaction is due to nervous influences. Excessive eating 
and drinking affect the left more than the right ventricle, but influence 
both sides to some extent. Habitual excessive beer-drinking is most 
striking in its effects, and doubtless acts through the constantly recur- 
ring overdistention of the blood-vessels, as well as through the excess 
of nutriment and direct stimulus conveyed to the organ. Pericardial 
adhesions may occasion continuous overaction of both ventricles. 

Any of the causes named may occasion hypertrophy or dilatation, 
or both. The degree of hypertrophy is dependent upon the previous in- 
tegrity of the heart muscle, the state of the general health, and the 
manner of action of the cause. Sudden strains are more likely to cause 
dilatation, and pure dilatation may result if the muscle of the heart is 
degenerated. This is illustrated by cases of acute dilatation of the heart 
in the course of infectious fevers. 

Pathological Anatomy. — Four forms of enlargement of the heart 
may be distinguished: First, the walls are thickened and the cavities 
are smaller than normal; this is known as concentric hypertrophy, but 
it is likely that the decreased size of the cavities is due to postmortem 
contraction; second, hypertrophy of the walls with normal cavities is 
spoken of as simple hypertrophy; third, hypertrophy with cavities of 
increased size is known as eccentric hypertrophy, or hypertrophy with 



DISEASES OF THE CIRCULATORY SYSTEM 515 

dilatation; and, fourth, there may be pure dilatation without hyper- 
trophy. In r^pertrophy the muscle substance is darker than normal 




Fig. 218. — A large hypertrophied heart contrasted with one of normal size. From a case 
of cardiorenal disease. (Norris and Landis, Jefferson Medical College Museum.) 




Fig. 219. — Hypertrophy of the left ventricle. 



and is increased in consistency. Microscopically, the fibers are in- 
creased in thickness, and there is probably also increase in the number 
of the fibers. The nuclei of the muscle are swollen and multiply; myo- 



516 



A TEXT-BOOK OF PATHOLOGY 



cardial degeneration (fibrofatty) is often associated. When dilatation 
is present the heart muscle is usually softer, more flabby, and generally 
somewhat lighter in color, due to associated degeneration. 

The shape of the heart varies from the normal. When the left 
ventricle is hypertrophied the organ is increased in length and extends 
further to the left than normal (Fig. 219). When the right ventricle is 
hypertrophied the organ assumes a rounded shape; its apex is less sharp 
and the transverse measurement of the organ is greatly increased. The 
weight and size of the heart may increase enormously, and the term 
cor bovinum is often highly appropriate. Weights of from 500 to 800 gm. 
are not infrequent, and may be greatly exceeded. Stokes recorded a 
case in which the weight was 1980 gm. 

Pathological Physiology and Results.— Hypertrophy is a relative 
process which serves to counterbalance the valvular or other impedi- 
ments to the circulation. To understand properly the mechanism and 
outcome of these conditions it should not be forgotten that the work of 
the heart never ceases, that the obstacle which has started the overwork 
resulting in enlargement may be irremovable, and that there is a limit 
beyond which the myocardium cannot reach. Since all the intrinsic 
causes of cardiac hypertrophy are of a nature including myocardial 
involvement {endocarditis, coronary disease) the muscle called upon to 
increase its work output is already handicapped and the great margin 
of safety inherent in it may be easily exhausted by sudden strain. It 
would seem that the heart attempts to reserve a portion of its power 
to hypertrophy, for it is to a certain extent a progressive process; occa- 
sionally, however, there may be excessive hypertrophy, but, as a rule, it 
is merely sufficient to maintain the circulation under ordinary conditions 
with less reserve power than is met with in health. In consequence, 
valvular lesions or arteriosclerosis may occasion no symptoms for a long 
time, provided the individual leads a quiet life. Eventually, however, 
when intercurrent diseases have determined cardiac weakness, or when 
the impediment to the circulation has advanced to an excessive degree, 
dilatation ensues and failure of the circulation is the consequence. When 
the left ventricle is at fault congestion of the pulmonary system occurs, 
and edema, hemorrhage from the lungs, or thrombosis with infarction 
of the lungs may take place. When the right ventricle fails, general 
systemic congestion, cyanosis, and dropsy are the consequence. 

Great hypertrophy, while it results from arterial disease, very fre- 
quently reacts upon the arteries and increases existing arterial disease, 
or occasions arterial disease when it has not previously existed. This 
is due to the increased force with which the blood is projected from the 
ventricular cavity and the -increased distention which the arteries suffer 
in consequence. 

ANEURYSM 

This is a rare condition of the heart. It is usually found in the ante- 
rior wall of the left ventricle, near the apex, but may affect any part of 
the auricles or ventricles (Fig. 220). Sometimes it is difficult to dis- 
tinguish dilatation from aneurysm. The usual cause of aneurysm is 



DISEASES OF THE CIRCULATORY SYSTEM 



517 



coronary obstruction, with resulting degeneration of localized areas of the 
wall of the heart. First, there is softening (myomalacia), and this may 
occasion acute aneurysmal dilatation and even rupture of the heart. 
In other cases the degenerated area becomes fibrous and subsequently 




Fig. 220. — Aneurism of the left ventricle. The left ventricular wall, which is elsewhere 
hypertrophied, is markedly attenuated on its left side at and above the apex. In this 
region a marked bulging, about the size and shape of a large duck egg, is seen. The endo- 
cardium in this region is covered with Calcareous plaques. The aortic and mitral valves 
show moderate sclerosis. (From Norris & Landis, Specimen from the Philadelphia Hospital.) 



dilates. Acute aneurysm of the heart wall may similarly occur in 
cases of mural endocarditis. Rupture in such chronic cases is a rare 
termination. 

Similar pouchings may occur in the valves, particularly the aortic, 
by inflammatory weakening of their stalk, and the condition has been 
called valvular aneurysm. This will of course interfere with closure, or 
by rupture give rise to a form of regurgitation. Such lesions are rare. 



518 



A TEXT-BOOK OF PATHOLOGY 



WOUNDS AND RUPTURE OF THE HEART 

Non-penetrating and even penetrating wounds of the heart wall 
are sometimes recovered from, the injury being repaired by scar-tissue 
or fibrous myocarditis. As a rule, penetrating injuries occasion rapid 
death by hemorrhage into the pericardium. Spontaneous rupture of 
the heart may be occasionally the result of severe strain of a normal 
heart, but, as a rule, it occurs when there is myocardial disease. Myo- 
malacia cordis, fatty degeneration, malignant endocarditis, and absces" 
are the conditions most likely to occasion rupture. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of acute miliary tuberculosis, 
affecting either the endocardium, myocardium, or pericardium; while 
caseous tubercles result from extension of tuberculous adenitis from the 
anterior or middle mediastinum. 

Syphilis is rare, but may occur in the form of gumma or of diffuse 
infiltration. In the latter case generalized fibrous myocarditis, indis- 
tinguishable in its gross appearances from non-syphilitic cases, may 
occur. Gummata may lie immediately beneath the pericardium or en- 
docardium, and after softening by degeneration may rupture on the 
surface. The degenerated areas may be unaccompanied by circum- 
ferential reaction, and may go into almost complete resolution without 
scar-tissue. On the other hand, the fatty area may have about it infil- 
trative and proliferative inflammation and other degenerations. The 
spirochetes are numerous in early stages. These areas are replaced by 
fibrous tissue whether or not they were originally associated with inflam- 
matory processes. They are probably due to colonization of spirochetes. 

Actinomycosis may involve the heart by extension from the medi- 
astinum or by embolism. White or grayish nodules are formed, and 
subsequently degenerate. 

NEW GROWTHS AND PARASITES 

Primary tumors of the heart are extremely rare. Sarcoma, fibroma, 
lipoma, myxoma, and myoma with muscle cells comparable to the cardiac 
cells have been met with, and usually occur in the form of wart-like 
growths projecting into the cavities beneath the endocardium. An 
important tumor is rhabdomyoma which has been discribed on page 222. 
Organized pediculated thrombi have frequently been mistaken for tumors. 

Secondary tumors are more common. Sarcomata of the medi- 
astinum may involve the pericardium, or even the heart wall, by direct 
extension, while secondary carcinomata and sarcomata may affect 
the myocardium by metastasis. In the latter instances nodular forma- 
tions are seen embedded in the heart muscle. 

Parasites. — Echinococcus cysts are occasionally seen beneath the 
endocardium or pericardium, and may rupture into the cavities of the 
heart, with resulting embolism. The cysticerci of Toznia solium and of 
T. saginata have occurred in man, but are more common in animals. 
The larval Linguatula rhinaria is a rare parasite of the heart. 



DISEASES OF THE CIRCULATORY SYSTEM 



519 



The Pericardium 

The pericardium is a membranous sac enclosing the heart and the root 
of the great blood-vessels. It is composed of a fibrous outer layer, and 
is lined within by flat endothelial cells. Normally it contains from 5 to 
50 c.c. of clear serous liquid. 

Partial or complete absence of the pericardium is sometimes seen, 
especially in cases of ectopia of the heart. Occasionally diverticula are 
present congenitally. 

CIRCULATORY DISTURBANCES 

Hyperemia of the pericardium may occur in valvular heart disease 
or in cases of tumor or aneurysm causing intrathoracic pressure. 

Hemorrhages. — Extreme passive congestion with ecchymotic hemor- 
rhages is found postmortem in cases of death from asphyxia. Small 
punctate hemorrhages are also occasioned by various infectious diseases 
and by certain poisons, as phosphorus. They are also seen in pernicious 
anemia, scurvy, purpura, and other blood diseases. 

Hemopericardium is a term applied to accumulation of blood in the 
pericardial sac. It may result from rupture of the heart or of aneurysms 
of the aorta, pulmonary artery, or coronary arteries. The serous 
effusion of inflammatory conditions of the pericardium may some- 
times contain considerable blood which has escaped from the small 
blood-vessels in the inflamed tissue. This is more common in inflam- 
matory effusions of the pericardium than of other serous membranes, 
and is particularly true of tuberculous and cancerous cases. 

Hydropericardium, or dropsy of the pericardium, may occur when 
passive congestion is continued, or as a part of anasarca. Occasion- 
ally the liquid is milky (chylous hydropericardium). Edema of the 
coronal fatty region as the bases of the ventricles is not uncommon 
in cases of acute general infections. It appears as if the mural layer 
were raised from the muscle by a yellow gelatinous fluid. 

INFLAMMATION 

Inflammation of the pericardium, or pericarditis, is the most 
important pathological process affecting this serous sac. 

Etiology. — Pericardial inflammations may be primary or secondary. 
In the former the irritants are conveyed to the pericardium through 
the blood, while in the latter the inflammation results from extension. 
Primary pericarditis occurs in association with various infectious dis- 
eases, notably acute rheumatism, scarlet fever, small-pox, influenza, and 
intense septic infections. These cases are termed "primary" because 
they are not extension processes, but hematogenic. It is also met with 
in the course of nephritis, either acute or chronic. Secondary peri- 
carditis may result from extension of inflammation from the pleura, the 
lung, the mediastinal glands, the sternum, the esophagus and stomach, 
or from the heart itself. 

In many instances, even when the pericarditis has occurred in the 
course of an infectious disease, micro-organisms are not discovered in 
the exudate; this may be due to the arrest of the micro-organisms in 



520 



A TEXT-BOOK OF PATHOLOGY 



the pericardial tissues; staphylococci, streptococci, pneumococci, in- 
fluenza bacillus, and tubercle bacilli have all been found. 

Pathological Anatomy. — Several varieties may be distinguished, 
though one form may merge into another. 

Fibrinous or Dry Pericarditis. — The first change noted in pericarditis 
is a dulness or lusterless condition of the surface of the membrane. 
Somewhat later distinct granulations, or a thin coating of fibrin, appear 
upon the surface, and this may increase until the deposit has a notable 
thickness. The movements of the heart may give the latter a marked 




Fig. 221. — Acute pericarditis (Bramwell). 



roughness or rugosity, and the term applied by older writers, cor villosum, 
is not inappropriate (Fig. 221). Microscopically, there is seen a deposit 
of granular or fibrillar fibrin upon the surface, while the endothelial 
cells are loosened and partly degenerated, and the subendothelial tissues 
are infiltrated with round cells. The blood-vessels are generally widely 
dilated, and punctiform hemorrhages may be observed. 

Serofibrinous Pericarditis. — The pericardial exudate rarely remains 
purely fibrinous in character. Usually there is some serous outpour- 
ing, and the sac becomes distended with more or less abundant tur- 
bid, serous liquid, in which flakes of fibrin are suspended. In such cases 



DISEASES OF THE CIRCULATORY SYSTEM 



521 



the fibrinous deposit is generally slight. Later the fluid may be reab- 
sorbed, leaving a simple fibrinous pericarditis. 

Purulent pericarditis, or pyopericardium, may begin as a fibrinous 
or serofibrinous process, or it may assume the suppurative form from the 
very start. In these latter cases the cause of the pericarditis is usually 
some intense general infection, as in puerperal pyemia and septicemia, 
or it may be a local infection, as in cases in which an esophageal or gastric 
ulceration has ruptured into the pericardium, or in which a caseous tuber- 
culous focus or purulent pleurisy has found a similar discharge. The 
pericardial sac is filled with purulent or seropurulent liquid, and the 
pericardium itself is covered with fibrinopurulent exudate. The super- 
ficial layers of the myocardium are frequently involved by inflammatory 
edema, myocarditis, or fatty degeneration. 

Hemorrhagic pericarditis is met with in individuals of low vitality 
and in persons suffering from scurvy, purpura, and similar affections. 
Pericarditis accompanying tuberculosis or cancer of the pericardium is 
specially prone to assume a hemorrhagic type. Usually the exudate is 
serous, but distinctly colored with blood; sometimes it is almost com- 
pletely hemorrhagic. 




Fig. 222. — Adhesive pericarditis, showing fibrin deposit, with new blood-vessels extending 

upward into it (Perls). 

Terminations of Acute Pericarditis. — Any of the forms described 
may persist for a considerable length of time without change, but usually 
certain alterations are noted. In the fibrinous variety or in the sero- 
fibrinous form, after the liquid has been reabsorbed, the visceral and 
the parietal pericardium lie in contact and are agglutinated by the 
exudate. Gradually the inflammatory processes beneath the fibrinous 
exudate extend into the fibrinous coating; connective-tissue hyperplasia 
and new formation of blood-vessels follow, and granulation tissue unites 



522 



A TEXT-BOOK OF PATHOLOGY 



the adjacent layers of pericardium. At the same time the fibrinous 
exudate is reabsorbed and subsequently organization of the granulation 
tissues is completed. Fibrous adhesions binding the two layers of the 
pericardium together ensue, and at times complete obliteration of the 
sac is the consequence (Fig. 222). In cases in which the in- 
flammation is slight, or in which the layers are kept apart by persistent 
serous exudate, the areas of inflammation gradually become thickened 
by new-formed fibrous tissue, and there remain upon the surface of the 
pericardium sclerotic spots, often spoken of as "milk spots." Occa- 
sionally portions of the fibrinous exudate remain unabsorbed, and 
together with the thickened membrane itself and the adhesions suffer 
calcareous infiltration. The heart may thus be encased in calcareous 
plates of considerable thickness. An infrequent termination is the 
retention of tabs of thick fibrin, covered by connective tissue, con- 
taining considerable fluid. These give the impression of small peduncu- 
lated cysts. 

Purulent pericarditis may terminate by discharge of the exudate 
into the esphaogus, stomach, pleura, or even into the bronchi, and by 
the subsequent adhesion of the two layers of the sac. In other cases 
gradual inspissation of the pus takes place and the cheesy residue may 
remain or eventually become calcareous. 

Associated Conditions. — While, on the one hand, pericarditis often 
follows inflammatory processes in the surrounding parts, it, on the 
other hand, not infrequently occasions disease of the adjacent structures. 
In most cases of severe acute pericarditis there is some associated in- 
flammation of the mediastinal structures and of the pleura contiguous 
to the pericardium. Cases which terminate with the formation of 
fibrous adhesions within the pericardial sac usually also present me- 
diastinal and pleural adhesions with the external surface of the peri- 
cardium (pericarditis interna et externa). This adhesion may at times be 
so firm that retraction of the lower chest occurs, in some cases moving 
with the heart beats. Myocarditis extending to a depth of 1 or 2 mm. is 
seen in nearly every case of pericarditis, and in long standing cases the 
coronaries may be so involved as to interfere with nutrition of the muscle. 
In cases in which considerable pericardial exudate is present the heart 
muscle is pressed upon and impeded in function, so that venous conges- 
tions are commonly observed. Adhesive pericarditis leads to hyper- 
trophy and, later, dilatation of the chambers of the heart. 

INFECTIOUS DISEASES 

Tuberculosis of the pericardium may result from the extension of 
pulmonary or pleural tuberculosis, or of tuberculous affections of the 
mediastinal glands. More rarely direct infection may occur through the 
medium of the circulation. Miliary tubercles are formed in the sub- 
serous and serous layers of the membrane, while the surface is covered 
with fibrinous exudation. The attendant pericarditis may be entirely 
fibrinous and the tubercles may be hidden from view by a thick deposit. 
In other cases there is serous, hemorrhagic, or purulent exudation, the 
latter especially in cases in which vomicae containing infective matter 
have ulcerated into the pericardial sac. Tuberculous pericarditis may 



DISEASES OF THE CIRCULATORY SYSTEM 



523 



terminate by gradual absorption of the exudate and fibrous adhesion, 
sometimes with calcareous infiltration. In other cases the necrotic and 
destructive changes characteristic of tuberculous processes elsewhere 
gain the ascendancy, and the disease proves fatal by the seriousness of 
the cardiac involvement. 

Syphilis is an extremely rare condition. Certain indurative changes 
in the pericardium have, however, been met with in association with 
syphilis of the heart. 

Actinomycosis may result from extension of actinomycosis of the 
mediastinum or of the lungs. 

TUMORS AND PARASITES 

Primary tumors, such as lipoma and fibroma, are extremely rare. 
Secondary carcinoma and sarcoma are more frequent. They result from 
similar growths in neighboring structures. Hydatid cysts and cysti- 
cerci are occasionally met with. 

PNEUMOPERICARDIUM 

Pneumopericardium (air in the pericardium) may result from per- 
foration of the sac in cases of fracture of the ribs or from penetration 
of foreign bodies through the esophagus into the pericardium. It also 
results from rupture of gastric or esophageal ulcers, and a certain amount 
of gaseous accumulation complicates purulent pericarditis when the 
exudate undergoes decomposition. The association of air and pus 
(pneumopyopericardium) more often results from secondary purulent 
inflammation after the development of pneumopericardium. 

The Arteries 

Anatomical Considerations. — The arteries and veins consist of 
three coats, called, respectively, the intima, or inner coat; the media, 
or middle coat; and the adventitia, or external coat. The intima con- 
sists of a layer of endothelial lining cells, below which there is a thick 
fibrous layer and then an elastic membrane. The middle coat con- 
sists of smooth muscle- and elastic fibers, while the outer coat is composed 
of fibro-elastic tissue. Small blood-vessels, the vasa vasorum, ramify 
through the adventitia and outer media, but the intima and immediately 
subjacent media are avascular, and probably nourished from within the 
vessel. The thickness and ultimate structure of vessel walls vary some- 
what with their size and function, a fact that to a minor degree affects 
their pathological histology. In the great arteries, the intima has a well 
developed museulo-fibrous layer between the endothelium and the internal 
elastic lamina and it is perhaps in this that the first effect of degenerative 
processes is felt. It is well to emphasize the elastic strands within the intima 
for upon them the rigidity of vessels depends. The resiliency depends 
upon the muscle in the media, a tissue generously supplied to the smaller 
vessels, elastic fibers being relatively fewer in this layer except perhaps just 
under the adventitia where it is difficult to state to which layer they belong. 
The relatively small amount of muscular tissue supplied to the great vessels, 
compared to the work they do, may be one reason why they suffer from 
degenerations of severe grade more than the small vessels. 



524 



A TEXT-BOOK OF PATHOLOGY 



The internal surface of vessels, lined as it is .with smooth flat cells, 
offers no impediment to the onrush of blood. Current is, however, di- 
verted and increased at branches and where a true dichotomy occurs 
there is a sharp angle against which the stream strikes, while when a 
branch comes off at an acute angle with the parent vessel, a crescentic 
sharp edge is produced. At such places emboli may catch, swelling or 
degeneration is prone to begin and thrombi to form. 

CONGENITAL DEFECTS 

Certain defects of distribution and of origin of the larger trunks 
have been referred to in the discussion of congenital defects of the heart. 
Very commonly there are anomalies in the arrangement of the periph- 
eral branches, but these are merely of anatomical interest. 

Hypoplasia. — A condition of importance is congenital smallness, 
or hypoplasia. This may affect the aorta and larger vessels together 
with the heart, or it may be confined to the blood-vessels, the heart 
being normal. Vascular hypoplasia has been especially met with in 
chlorotic girls, and also occurs in cases of status lymphaticus. The 
aorta is sometimes so small that it barely admits the little finger, and 
the walls are usually correspondingly decreased in thickness. Decided 
elasticity of the coats of the vessels may be observed. 

HYPERTROPHY 

This occurs when a collateral circulation is established in conse- 
quence of obstruction of an artery. Similarly, in the new formation of 
tissue the blood-vessels first formed are delicate vascular channels, which 
subsequently hypertrophy and are converted into well-developed arte- 
rioles. In this case there is a uniform overgrowth of each of the com- 
ponent parts of the blood-vessel, and not a mere hyperplasia of one 
or another coat. There is also some increase in the size of vessels from 
excessive and prolonged physical labor and this may in time lead to 
degenerations and thus to arterio-fibrosis. 

ATROPHY 

This may occur in a part which is undergoing general atrophy, or 
where there is pressure and anemia of certain areas. Degeneration of 
the walls usually takes place in such cases, and the conditions are, there- 
fore, more properly considered among degenerations. 

DEGENERATIONS 

Fatty Degeneration. — Any one of the coats may be affected, but 
the process is most common in the intima. Fatty degeneration is one 
of the important factors in atheroma; more rarely it occurs as an inde- 
pendent affection of the blood-vessels. In the latter case disturbances 
of circulation and toxic agencies in the blood are the immediate causes. 
Small white or yellowish spots or streaks may be seen in the endothelium, 
and microscopically the endothelial cells may be found granular or filled 
with fat-drops. In cases of greater severity there may be actual erosion 
of the endothelial surface. In cases in which the media is affected the 



PLATE 9 




Acute aortitis. From a woman aged twenty-eight. Septicemia following abortion. 
Specimen stained concurrently with Sudan III and Scharlach R. Acute fatty degenera- 
tive areas deeply stained. Normal aorta should exhibit no more stain than shown in 
palest areas. (Norris and Landis. Specimen from Jefferson Medical College Museum.) 



DISEASES OF THE CIRCULATORY SYSTEM 525 

muscle-cells undergo fatty degeneration. Fatty degeneration may occa- 
sion rupture of the blood-vessels, or calcareous infiltration may ensue. 

Calcareous Infiltration is the common termination of atheroma, 
but sometimes calcification of the intima or media, or even of the entire 
wall of the vessel, may be observed vvithout arteriosclerosis. The 
process is most common in the intima and media, and, aside from the 
instances in which it is a part of atheroma, it may occur in consequence 
of circulatory disturbances, or as the result of bone disease, with de- 
struction of osseous tissue and surcharge of the blood with earthy salts. 
The salts are disposed either within the cells or irregularly through the 
tissue either as granules or continuous sheets that can be seen grossly. 

Hyaline degeneration is a condition the nature and uniform char- 
acter of which remain in doubt. A form of hyaline degeneration is very 
common in the hyperplastic tissue of arteriosclerosis, and is generally the 
first evidence of beginning degeneration. It is met with in small blood- 
vessels which are obstructed by thrombi, or which are subjected to de- 
structive pressure by inflammatory new growths or other causes. Not 
infrequently it is due to infectious fevers or intoxications, and in these 
cases the small arteries and the capillaries are prone to be affected. 
Hyaline degeneration of the blood-vessels is the striking feature of 
certain cylindromata (see Fig. 18). The artery may show a uniform or 
a more nodular, firm, opaque thickening, and under the microscope the 
subendothelial tissue, the adventitia, or the entire wall of the blood- 
vessel may be found converted into vitreous substance. Rupture of the 
affected vessel is a not infrequent result. 

Amyloid infiltration commonly begins in the blood-vessels of the 
parts of the body in which this disease is found. In the kidneys the 
capillary tufts of the Malpighian bodies, and in the spleen the capil- 
laries within the follicles, are first affected, at which places the substance 
is laid down first beneath the endothelium, growing and causing the 
essential cells to atrophy thus finally giving the impression that the 
whole part had become amyloid. Amyloid disease is sometimes found in 
the intima of the larger blood-vessels, occurring in small linear or punc- 
tate areas, and scarcely to be recognized excepting by chemical tests. 

INFLAMMATION 

Inflammation of the arteries may affect the inner, the middle, or 
the outer coat, and in a strict anatomical sense the terms endarteritis, 
mesarteritisj and peri-arteritis are justified; but, as a rule, all three coats 
are more or less involved at the same time, and no practical distinction 
can be drawn. There may be acute or chronic inflammation. 

Acute Arteritis 

Acute arteritis may be of two kinds: a suppurative or necrotic 
form and a productive form. 

Acute suppurative arteritis occurs in the arteries traversing areas 
of suppurative inflammation, and results from the extension of the 
suppurative process. It may also occur in consequence of the lodg- 
ment of infected emboli or as a result of infection of thrombi within 
the vessels. 



526 



A TEXT-BOOK OF PATHOLOGY 





Fig. 224. — Septic thrombo-endo-arteritis of coronary in vegetative endocarditis. 



DISEASES OF THE CIRCULATORY SYSTEM 



527 



When the process extends from without, the adventitia and then 
the media are infiltrated with round cells, and in cases of some of the 
larger vessels there may be visible points or collections of pus. The 
process may extend as deeply as the intima, and may completely per- 
forate the wall of the vessel, leading to hemorrhage. The intima itself 
is not directly involved by the suppurative process from the lack of inde- 
pendent blood-supply, but the emigrated leukocytes may infiltrate it, 
and degenerative changes are common in the endothelium. Where the 
process begins by infection within, as through softened thrombi or in- 
fectious emboli, there is first necrotic or degenerative destruction of the 
intima, and subsequently infiltration of the media and adventitia with 
emigrated round cells (Fig. 224). 

During, and indeed following, many acute infections, notably malig- 
nant endocarditis, meningitis, streptococcus and pneumococcus disease, 
there is an endoarteritis with its special lesions in and under the endothe- 
lium. This form affects chiefly the small vessels producing in them an 
endothelial swelling, prominence and possible multiplication of subjacent 
muscle and fibrous tissue cells, and what seems to be some edema. This 
change may end in a thickening of the inner layer at this point or the 
outer coats may be involved if ulceration and deep infiltration follow. 
In the latter case hemorrhage may result or, if resistance be sufficient, an 
aneurysm may form. In the former case the thickening takes the nature 
of a thrombosis with proliferation of the intimal tissues, the elastica being 
much fragmented, and the replacement of the thrombus by connective 
tissue, endarteritis proliferans. 

Productive endarteritis is seldom really acute although it may follow 
upon an acute lesion as just described. The changes usually discussed 
under this term may be classed as twofold — a rather slowly progressive 
affair due to local trophic changes or the more subacute generalized 
process known as thromboangitis obliterans. The first form is seen in 
vessels that close their lumen in atrophy of the breast or ovary in the 
recession of these organs, or accompany chronic diseases — chronic neph- 
ritis or tuberculosis. In such cases it seems as if the process were one of 
simple proliferation of internal structures since the internal elastic 
lamina is usually preserved entire, while the new growth of fibrous tissue 
remains covered with endothelium, little if any different from normal. 
There is rarely a thrombosis springing from the walls of these vessels, 
although hyaline bodies are at times seen within them probably from 
obstruction to blood flow. The media may show some fibrosis. The 
other form, endarteritis or thromboangitis obliterans, has many features 
of an infectious or toxic process and has been especially noted in young 
Jews of foreign birth. 

The principal lesions are to be found in the lower extremities and the 
symptoms are lameness, pain, tingling and in some cases gangrene. In 
so far as the exact origin of the lesions is concerned, no unanimity of 
opinion exists but by most writers it is thought to depend upon intra- 
vascular thromboses which become organized. 

The changes affect mainly the intima and the adventitia, both of 
which coats are densely infiltrated with round cells. The thrombus, 
which was the original cause of the arteritis or which has resulted there- 



528 



A TEXT-BOOK OF PATHOLOGY 



from, becomes similarly infiltrated with round cells, and as the process 
advances is found to be penetrated by fibroblastic cells, which probably 
take origin from proliferation of the intimal cells or from other connective- 
tissue cells in the walls of the vessels. In moderate grades the elastica 
remains intact although some records exist in which dense cellular infil- 
tration with destruction of this wavy line were observed. New blood- 
vessels spring from the vasa vasorum and penetrate the thrombus, and a 
lesser number of new vessels may enter the thrombus directly from the 
lumen of the occluded vessel itself (see Fig. 10) ; partial canalization may 
occur. The process of organization takes place as in the serous surfaces 
generally, and as new connective tissue is formed the thrombus is gradu- 




Fig. 225. — Nodular productive endarteritis. 



ally removed and the lumen of the vessel may become completely oblit- 
erated. Less extensive involvement of the vessel may lead to the formation 
of bands of adhesion passing from one side of the vessel to the other, 
and causing considerable deformity and distortion. The media usually 
takes very little part in the process, being merely infiltrated with round 
cells, but the entire wall of the vessel may become fibroid in the terminal 
stages and the separate coats may be indistinguishable. 

The principles involved in the foregoing are to be applied to the 
closure of a severed or ligated vessel. Intravascular coagulation having 
occurred, in either case it is by internal proliferation and vascular new 
growths from the media that organization of the clot and obliteration of 
the lumen take place. 

Peri-arteritis Nodosa. — Under this name has been described a form 
of productive inflammation of the adventitia leading to the formation 



DISEASES OF THE CIRCULATORY SYSTEM 



529 



of fibrous nodules. In some of these cases there is no doubt a different 
pathology, as in the instances in which the intima has been found to 
protrude in a hernia-like manner through defects in the media, but in 
most cases the disease is a productive peri-arteritis (see also under 
Aneurysm). The medial changes seem secondary, this coat showing 
necroses and hemorrhages, and finally atrophy. Intimal thickening 
occurs later. The disease is an acute one frequently and has been as- 
cribed to syphilis. The etiology cannot always be established. 

Arteriosclerosis 

Arteriosclerosis, or endarteritis chronica deformans, is a chronic 
degenerative and inflammatory disease of the arterial system. It may 
be confined to the arteries, or may be more extensive, involving the 
capillaries as well, when the term arteriocapillary fibrosis (Gull and 
Sutton) is applicable. Sometimes the veins also are involved, and for 
this condition the name angiosclerosis has been proposed. 

Etiology. — Arteriosclerosis is a physiological process of old age, and 
probably begins as early as middle life in most persons. The earlier 
occurrence of the disease or the more extreme grades of its severity are 
dependent upon a variety of causes, among which certain chronic intoxi- 
cations — viz., syphilis, gout, chronic alcoholism, and chronic nephritis — 
are prominent. An important cause is muscular exertion, and it is not 
uncommon to find marked instances in persons whose life or occupation 
has subjected them to unusual muscular strain. There is a general 
tendency to lay to continued high blood pressure a considerable part in 
the causation of the condition, but it is at present impossible to convict it 
of a primary etiological role for, with arteriosclerosis, are so often com- 
bined other lesions, the cause of or incident to increased pressure — 
cardiac and renal disease. Its importance increases in the presence of 
other factors favoring disease of the media. Cachectic conditions of 
various kinds may play a part, as in cases of carcinoma, tuberculosis, 
or inanition; and sometimes the chronic arterial disease follows after 
acute infections, such as rheumatism, scarlet fever, typhoid fever, and 
the like, while experimental evidence supports clinical suspicion that long 
continued staphylococcus disease stands in some relation to the arterial 
changes. We are inclined to think that too little attention has been paid 
to chronic intestinal intoxication from improper diet, inflammation or 
overeating. It is a matter of human experience to be aware that several 
of the above factors may be present in one person. 

Productive and degenerative diseases of the vessels occur but rarely 
in the lower mammals and birds but in them, according to the investiga- 
tions of one of the authors, are most often encountered in orders whose 
habits demand severe or protracted efforts in fight or flight, in those whose 
diet contains a high percentage of protein and whose gastrointestinal 
tract is most often the seat of inflammation. In mammals the media is 
most often diseased, in birds the intima. Parrots, however, frequently 
show lesions corresponding to senile arteriocapillary fibrosis. 

Pathogenesis. — Not a little difference of opinion has existed in 
regard to the manner in which the recognized causes of arteriosclerosis 
operate. At first it was generally maintained that the infectious and 

34 



530 



A TEXT-BOOK OF PATHOLOGY 



toxic agencies directly irritate the inner lining of the blood-vessels and 
produce inflammatory thickening. This view has, however, been quite 
generally abandoned, and it now seems established that degenerative 
changes and loss of elasticity in the vessel wall are the result of the primi- 
tive causes, and that the hyperplastic processes in the intima and other 
parts of the arterial wall are the ultimate expression of a reparative 
process. 




Fig. 226. — Degenerative deforming sclerosis and Fig. 227. — Monckeberg type of 
atheroma of aorta. medial sclerosis, femoral artery. 

In cases of arteriosclerosis occurring in old age, for example, the 
first disturbance of the blood-vessel consists in a loss of elasticity in 
the muscularis and an overdilatation of the blood-vessels. Secondarily, 
in consequence of this loss of elasticity, there is a hyperplasia of the 
intima, which serves in some measure to contract the lumen of the 
vessels and thus restore the vascular channels to their normal calibre. 
In cases of purely pathological arteriosclerosis similar functional weak- 
ness of the muscularis or more pronounced and demonstrable degenera- 
tive changes may be the primary conditions, which in the end lead to 
arteriosclerosis. In all cases the direct effect of elevations of blood-pres- 



DISEASES OF THE CIRCULATORY SYSTEM 



531 



sure may play an important part, and in cases of muscular overwork or 
of hypertrophy of the heart the increased vascular tension may be the 
all-important cause. It may be said that generally sclerotic changes 
occur most frequently in vessels that feel, or are subject to, frequent 
alterations in blood-pressure. 

In explaining the minuter origin of the vessel-wall changes one must 
think of those which begin as a chronic productive inflammatory process 
and those in which the change is degenerative at first. The line between 
is by no means sharp, and the latter may be but a forerunner of the 
former. The inflammatory kind is exemplified by syphilitic arteritis 
(q. v.) ; the degenerative, by the senile form. 




Fig. 228. — Monckeberg's sclerosis, a cross section of the vessel showing medial calcifica- 
tion and the sinking in of intima corresponding thereto. 

It has been supposed by some that degenerations of the media, 
with giving away of its muscular, elastic, and fibrous tissue, are due 
to compression by proliferated intimal endothelium acting under toxic 
influences. These alterations have been explained by others as purely 
toxic degenerative medial changes. Koster pointed out that round-cell 
infiltration surrounding the small branches of the vasa vasorum in the 
media is the earliest change in some instances. Rupture of the elastic 
coat is doubtless an important early change in many cases. Considerable 
round-cell infiltration may be seen in the deeper layers of the intima and 
in the media, and new formation of blood-vessels may be quite pro- 
nounced. Such changes, however, are not usual and not characteristic. 

Basing his conclusions upon the fact that if the intima of an early 
sclerotic patch be stripped off, a separation of the endothelial cells will be 
found, Aschoff believes that serum is allowed to penetrate the inner 
lining; this it is thought lays down colloids, and fats wmich later are 
split into glycerin, cholesterin and soaps from which there arise, globules 
of fat, refractile cholesterin esters and calcium deposits when the fatty 
acids of the soaps have been removed. These new bodies may take part 
in inciting proliferative changes in the intima. 

Although one cannot state today the exact operation of the cause of 
arteriosclerosis, the essence of the process is a proliferation of the intimal 



532 



A TEXT-BOOK OF PATHOLOGY 



tissues, a fibrillation of the elastic laminae and degeneration in the media. 
In most forms the new tissue in the intima undergoes degeneration also, 
while the media is replaced by functionally inactive tissue. 



Fig. 229. — Earliest change in degenerative or atheromatous arteriosclerosis in aorta. 
The intima is thickened, large pale cells appear, vacuoles (fat) appear and nuclei may be 
more numerous in the media. 



r 




Fig. 230. — Late stage of degenerative atheromatous arteriosclerosis in aorta. The 
intima at the right is advancing bej^ond the stage as shown in previous picture and, as one 
goes to the left, the atheromatous process increases to the pultaceous material seen in the 
centre or to calcification, beginning at the extreme left. The media becomes condensed, 
nuclei disappear and elastic fibres, shown by clear areas, become extremely thin and broken. 

Pathological Anatomy. — Arteriosclerosis may be a diffuse process, 
affecting more or less uniformly a large part of the arterial system, or 
it may be a circumscribed or nodular condition. In the latter instances, 
which are most common in the aorta and large vessels, there are seen 
on the inner lining of the vessel nodular elevations, varying from the 



DISEASES OF THE CIRCULATORY SYSTEM 



533 



merest points to areas the size of a small coin. These are raised a milli- 
meter or two above the surface, and in their earlier stages have a 
translucent grayish color;. they are covered with smooth, unaltered endo- 
thelium. Later, degenerative changes ensue and the nodule becomes 
dull-white or yellowish in color, and finally calcification may render it 
extremely hard (atheromatous plate). The focus may, on the other hand, 
soften completely by degeneration and may discharge into the lumen of 
the vessel, leaving a necrotic, ulcerated patch (atheromatous ulcer). 
Calcareous change may now occur, and the surface may be covered 
with thrombotic fibrinous deposits. These circumscribed areas of 
arteriosclerosis may be few in number^and widely separated. In such 
cases the aorta, particularly where it gives off branches, is the favorite 
seat. In other cases the plates may be so numerous and thickly set that 
the aorta is completely transformed. 

Diffuse arteriosclerosis is especially frequent in elderly persons, and is 
more common in the small vessels than in the aorta. Sometimes it is 
associated with the nodular 
form; sometimes the nodular 
change is wanting, in which 
case it is of the nature of 
obliterating arteritis, the out- 
standing features of which 
are calcification of the media 
and a fairly uniform intimal 
overgrowth. 

Microscopically, the nodu- 
lar elevations are found to 
consist of deeply staining cells 
of elongated character, the 
hyperplasia affecting the sub- 
endothelial part of the intima 
in the earliest stages. There 
is swelling of the endothelia, 
with fatty detritus and glo- 
bules collecting in these cells, 

and the connective tissue cells, possibly the collection of fibrin upon 
the surface, and the appearance of polynuclears. Subsequently degen- 
eration of the nodule becomes manifest. At first the intercellular mate- 
rial assumes a hyaline character and becomes glassy in appearance. The 
cells themselves may suffer fatty degeneration from pressure. Later the 
whole area undergoes myxomatous or, more particularly, fatty degenera- 
tion, and breaks down, forming a pultaceous detritus in which fat-drops 
and cholesterol plates are prominent (Fig. 231). Eventually calcareous 
granules are deposited. Early in the stage of degeneration the internal 
elastica breaks up into several thin layers or^ may dissolve entirely 
at one or more points under the plaque. In diffuse arteriosclerosis the 
changes resemble those met with in the nodular form. There is wide- 
spread thickening of the arterial coats involving the subendothelial 
tissue at first and later the entire wall. Secondary degenerative changes 
in areas or patches occur in the large arteries, but are less common in the 




Fig. 231.- 



- Atheromatous degeneration of a cerebra 
artery (Karg and Schmorl). 



534 



A TEXT-BOOK OF PATHOLOGY 



small vessels. The endothelium attempts repair over defects except 
calcareous ulcers. It is heaped up over subintimal and medial swellings. 

Fatty degeneration and calcification may also be apparent in the 
media, and more or less hyperplastic connective-tissue overgrowth 
may be seen in the adventitia. The calcium deposits may take the form 
of amorphous granules, irregular masses of bone salts or an attempt may 
be made to simulate bone formation, even with marrow spaces and cells. 
In cases of diffuse arteriosclerosis the media, as a rule, is thickened by 
hypertrophy of the muscle-fibers as well as by sclerosis; but in the nodular 
forms the media is usually distinctly thinner than normal. This hyper- 
trophy only affects those that are wholly intact and is compensatory, as 
destroyed media muscle-fibers do not regenerate. Repair occurs in direct 
relation to the freedom of blood-supply to the diseased parts, either from 
the vasa vasorum or from the lumen of the affected vessel. This brings 
nutrition and stimulates cells of the fibroblastic series. Even elastic 
fibers may be restored. 

In that type of arteriosclerosis to which Monckeberg has given his 
name, the gross and minute anatomy vary considerably from the above 
and indeed the history of the case may be of some significance. It occurs 
sometimes in senile persons but has been frequently seen in diabetes in 
which disease it has seemed to be related to gangrene. The extremities 
are usually involved and the trunk vessels may be free of sclerosis. The 
process starts as a fatty and hydropic degeneration of the medial muscles 
upon which calcification in separated plaques quickly succeeds. This 
gives the vessels an irregular outline and occasions sacculations, over 
which the intima may attempt to grow in order to restore the lumen; this 
effort is often very slight and practically always ineffectual for the distor- 
tion is increased by one process or the other. Obliteration of the lumen 
is uncommon. 

Results. — In the smaller blood-vessels, particularly in those of 
the brain, the hyperplastic process in the intima may proceed to such 
a degree that the lumen of the vessels is almost completely obliter- 
ated (endarteritis obliterans). Complete obliteration may take place 
by direct union of the opposite walls of the vessel, or there may be first 
thrombosis, with subsequent organization of the thrombus. In the 
aorta and in some of its larger branches the loss of elasticity consequent 
upon the formation of fibrous tissue and subsequent degenerations leads 
to gradual dilatation of the blood-vessel walls, either in the form of dif- 
fuse ectasia or of localized aneurysmal sacs. Sometimes the degenera- 
tion of the diseased area occasions spontaneous rupture of the vessel. 

Portions of the thrombotic deposits upon the roughened lining of 
the vessels, or portions of the degenerative tissue itself, may be dis- 
charged into the circulation, and may be carried to the peripheral parts 
as emboli. 

Changes in Other Organs. — Diffuse arteriosclerosis places an im- 
pediment upon the heart which leads to hypertrophy of its walls, and, in 
particular, of the walls of the left ventricle. 

When the process affects the small blood-vessels in the substance 
of the various organs, degenerative changes due to anemia and react- 
ive hyperplasia of connective tissue are common results. Thus, in 



DISEASES OF THE CIRCULATORY SYSTEM 



535 



cases of sclerosis affecting the cerebral vessels, cerebral softening is 
commonly met with, while in cases in which the branches of the coronary 
or of the renal arteries are affected, degeneration and fibroid changes are 
seen in the heart and kidneys. 

INFECTIOUS DISEASES 

Syphilis may involve the blood-vessels in a variety of ways. No 
doubt syphilitic infection is a most potent cause in the production of 
arteriosclerosis, but more specific involvement of the vessels occurs. 
Recent investigators have described a special type of arteriosclerosis 
as syphilitic. Unlike senile arteriosclerosis, it seems an inflammatory 
process from the start, an assumption supported by the close relation of it 
and the Wassermann test, the discovery of the cause of syphilis in the 
tissue and the statement from one source that injections of the spiro- 
chetes produce in animals a lesion like the spontaneous one. In the 



■ %| 

Fig. 232. — Syphilitic aortitis showing irregular productive intimal overgrowth of fibrous 
tissue, fibrous tissue and round cell increase in the media, a gumma, increase in number of 
vasa vasorum and perivascular round cell mantle. 

presence of syphilis, however, the factors that form arterial disease, as 
before discussed, increase the probability of its development. It occurs 
chiefly in males during early middle life and leads to aneurysm in about 
one-fourth of the cases. The aorta is notably affected, the lesions pre- 
senting themselves as scar-like changes which cause marked deformity 
of the endarterial surface in the shape of longitudinal ridging and irregu- 
lar gray, yellow and white patches which encroach on the lumen of the 
main vessel but especially upon that of the small branches which are 
sometimes reduced to mere points. Extension may occur down the 
aorta into the thoracic or abdominal division but the stretch near the 
heart is most characteristically altered. It very frequently proceeds 
toward the heart and affects the valve bases or the leaflets themselves. 
Microscopically, the media and adventitia are much more decidedly in- 
volved than in ordinary arteriosclerosis. The process begins as a peri- 
vasa-vasorum infiltrate of round and plasma cells in the media and 




536 



A TEXT-BOOK OF PATHOLOGY 



adventitia, shortly followed by atrophy of muscularis and elastica. The 
mesial elastic strand may degenerate and completely disappear while the 
internal lamina may be fractured at places, but there is not the 
longitudinal fibrillation seen in degenerative sclerosis. Actual gumma 
formation is common. 

In areas of syphilitic infiltration and induration or adjoining gummata 
the small blood-vessels present noteworthy changes. The intima and the 
adventitia, but particularly the former, undergo great hyperplasia, and 
the lumen of the vessel may be almost obliterated. The changes are first 
noted in the intima, where large numbers of epithelioid cells are formed, 
while, later, infiltration of round cells is observed. The adventitia is 
similarly, but less extensively, affected. The outcome of this arteritis 
is fibrous scar-tissue; atheroma and calcification occur very seldom 
in pure syphilitic arteritis. The scar-tissue, while dense, is without 
elasticity, so that at the points of cicatrization variations of lumen occur 
(syphilitic aneurysms, q. v.). 

Tuberculosis. — The arteries may become involved in areas of tuber- 
culosis, though, as a rule, they prove resistant for a long time. Typical 
caseous degeneration may be seen in the walls of the blood-vessels, 
beginning in the adventitia and gradually advancing toward the inte- 
rior. In the lungs these changes are not infrequently seen in the walls 
of tuberculous cavities, and as a result there may be small aneurysmal 
dilatations at the points where the wall of the vessel has become eroded 
and weakened. It is from such vessels that the severe hemorrhages of 
the late stages of phthisis take place. Sometimes the blood-vessels 
of the tuberculous area present productive change leading to great 
thickening of the adventitia and of the intima, and there may be con- 
siderable narrowing of the lumen of the vessel. This, however, is less 
common than the degenerative changes before alluded to. There may 
be solitary tubercles in the intima or subintimal layers of the media. 
Thej' are of ordinary architecture and may open into the vessel lumen. 
They start as endothelial tubercles when the organisms are taken up 
by these lining cells in capillaries. 

ANEURYSM 

Definition. — By aneurysm is meant a more or less localized dilata- 
tion of the arterial walls. The term has, however, been applied also to 
collections of blood outside of an artery enclosed by an adventitious 
wall dependent entirely upon a traumatic rupture of the vessel. The 
name jalse or spurious aneurysm has been specially applied to such cases, 
while the term true aneurysm is reserved for such as conform to the first 
definition. It is preferable to confine the single word aneurysm to the 
latter. 

Etiology. — Aneurysms are always due to some weakness of the 
walls of the blood-vessel and to the distending force of the blood within. 
It is, therefore, most common to find the disease in persons beyond the 
age of forty or forty-five years, and particularly in those who have 
acquired arteriosclerosis. Among the remote causes, therefore, are 
those of arterial disease — syphilitis, gout, alcoholism, lead-poisoning, 
and other chronic intoxications. Of all the individual causes, syphilis is 



DISEASES OF THE CIRCULATORY SYSTEM 



537 



most important. Sometimes it would seem that there is hereditary weak- 
ness of the arterial coats, and instances of aneurysm occurring in succes- 
sive generations have been recorded. Even congenital aneurysms have 
been observed. As contributing causes may be ranked all conditions 
which increase the blood 7 pressure. Thus, laborious occupations, hyper- 
trophy of the heart, and diseases which occasion constant excess of blood- 
pressure give rise to arterial degeneration and also to dilatation of the 
vessel in a purely mechanical way. Sudden aneurysmal dilatation of a 
weakened vessel may occur after severe straining efforts, as in coughing, 
during labor, in the straining of obstinate constipation, etc. 

More acute degenerative changes in the blood-vessels may lead to 
aneurysmal dilatations. Thus, in the rare instances of acute aortitis in 
association with malignant endocarditis, small aneurysmal dilatations 
and even rupture of the aorta may occur. Embolism plays a part 

in a similar manner. Sometimes a cal- 
careous embolus from a diseased valve 
of the heart, or from an atheromatous 
plate in the aorta, may lacerate the walls 
of a peripheral vessel, leading to the 
formation of a dilatation. In other 
cases infected emboli (as in malignant 
endocarditis or thrombosis with second- 
ary degeneration of the clot) lodge in 
the peripheral vessels and occasion acute 





Fig. 233. — Worm aneurysm of the horse Fig. 234. — Miliary aneurysm of the brain. 
(Leuckart) . 



inflammatory or degenerative lesions of the walls, and eventually 
aneurysmal dilatation. These cases are analogous to the aneurysms 
of lower animals caused by animal parasites (Fig. 233). 

The artery most commonly affected is the aorta, and in particular 
the thoracic portion. A majority of the aneurysms affecting the thoracic 
part of this vessel arise from the ascending limb, and not rarely it is one 
of the sinuses of Valsalva that first suffers dilatation. Next to the 
aorta in point of frequency, the popliteal, femoral, carotid, subclavian, 
innominate, axillary, and iliac vessels are affected. 

An interesting form, and one of great frequency and clinical sig- 
nificance, is that which affects the small blood-vessels of the brain, par- 
ticularly the branches supplying the lenticulostriate body. This is the 
so-called miliary aneurysm, which is commonly the cause of cerebral 



538 



A TEXT-BOOK OF PATHOLOGY 



hemorrhage (Fig. 234). It is simply a small saccular aneurysm due to 
weakening of the blood-vessel walls by sclerosis or degeneration. 

In some cases of the condition described as peri-arteritis nodosa 
(see p. 528) there has been discovered a hernia-like projection of theintima 
through defects of the media. These have been recorded as instances 
of congenital aneurysm, but this explanation does not suffice for all 
cases. (See Arteritis.) 

In phthisical lungs there are often found somewhat similar hernia- 
like aneurysms, due to erosion of the adventitia and media by the tuber- 
culous process; and it is from these that 
the severe hemorrhages of the late stages 
of phthisis occur. 

Pathological Anatomy. — Aneurysms 
may be of three kinds: (1) Those in which 
there is quite general dilatation of all of 
the coats of the vessel, which, therefore, 
present themselves in the form of a more 
or less uniform dilatation (ectatic aneurysm) ; 

(2) those in which a local weakening leads 
to the formation of a saccular pouch, often 
communicating with the artery by a nar- 
rowed orifice (saccular aneurysm) ; and 

(3) those in which a rupture of the intima, 
and usually of portions of the media as well, 
has|led [to infiltration of blood between the 
tunics of the vessel wall (dissecting 
aneurysm) . 

1. Ectatic Aneurysm. — There is more 
or less uniform dilatation in these cases, 
and there may be distinguished fusijorm 
or spindle-shaped and cylindrical varieties, 
according to the shape assumed (Fig. 235). 
In some instances the vessel is rendered 
tortuous by the unequal involvement of 
different portions, and to this form the 
term cirsoid aneurysm may be applied. 
The same term, as well as the name 
anastomotic aneurysm, is given to certain 
conditions of the arteries of the scalp and 
other parts which lead to the formation of 
tortuous vessels standing out prominently beneath the skin; but these 
are instances rather of hypertrophy of the coats, with increase of 
length and thickness of the walls, without, in reality, any aneurysmal 
dilatation at all. 

In ectatic aneurysms the intima and adventitia are usually thickened, 
and there are generally atheromatous patches in the former. The media 
is generally thinner than normal, and may be actually deficient in places. 
Ectatic aneurysms may show a certain amount of thrombosis in the form 
of laminated clots, when there are pouchings or inequalities in the dila- 
tation, but very frequently there is no thrombosis. 




Fig. 2 3 5. — Cylindrical and 
somewhat cirsoid aneurysm of the 
abdominal aorta: an opening has 
been made to show the clot within 
(from a specimen in the Museum 
of the Philadelphia Hospital). 



DISEASES OF THE CIRCULATORY SYSTEM 



539 




Fig. 236. — Saccular aneurysm of the arch of the aorta, projecting forward and attached to 

the ribs (Ziegler). 




Fig. 237. — Saccular and partly ectatic Fig. 238. — Saccular aneurysm of the 

aneurysm of the descending part of the arch ascending part of the arch of the aorta 

of the aorta (from a specimen in the Museum (from a specimen in the Museum of the 

of the Philadelphia Hospital) . Philadelphia Hospital) . 



540 



A TEXT-BOOK OF PATHOLOGY 



2. Saccular Aneurysm. — This is the most important variety. Ac- 
cording to Thoma and others, the first step in the process is the weak- 
ening or giving way of the media, followed by gradual dilatation of the 
intima and adventitia. There results a saccular dilatation commu- 
nicating with an artery, from which it arises by a more or less narrow 
orifice (Figs. 236-238), representing the place at which a very decided 
loss of tissue, by degeneration, has occurred. The expansile blood 
pressure dilates still further the sac thus formed and one must imagine 
a whirl of blood within the aneurysmal cavity. Under the microscope 
the edges of the opening are seen to consist of the ordinary walls of the 
vessels, usually sclerotic, while the part that is turned out to form the 
sac consists of fibrous connective tissue formed by the surrounding 
tissues over which the intimal endothelium tries to grow. When this is 




Fig. 239. — Aneurysm of the aorta: erosion of the sternum and projection of the sac 

beneath the skin. 

imperfect, as is usually the case, thrombosis begins, and makes an effort 
to fill up the cavity; the clots organize and fuse with the connective 
tissue wall of the aneurysm, a process that may in small sacs fill up the 
dilatation. When endothelium is successful in growing over the inner 
surface, it in time degenerates or disappears because it is inadequately 
supported by a media; it may even show atheromatous plates. In 
small aneurysms and those recently begun, much more of the coats 
remains, but the original disease and the constant dilatation soon causes 
them to degenerate. 

• The tissues surrounding the aneurysm are pushed aside or com- 
pressed, and may suffer extensive necrosis. In cases of aneurysm of the 
thoracic aorta the sternum and ribs may be eroded, and the aneurysm 
may project beneath the skin anteriorly and eventually rupture (Fig. 
239). In other cases the trachea, bronchial tubes, or lungs are com- 



DISEASES OF THE CIRCULATORY SYSTEM 



541 



pressed, and rupture takes place through the trachea or bronchi (Fig. 
240). In still others the sac projects posteriorly, erodes the bodies of 
the vertebrae and ribs, and may compress the spinal cord or may project 
.beneath the tissues of the back. Those developing in the intraperi- 




Fig. 240. — The trachea, showing perforation of an aneurysm of the aorta (from a specimen 
in the Museum of the Philadelphia Hospital). 

cardial portion of the aorta or extending into it, may rupture then or 
form an arteriovenous anastomosis with one of the large pulmonary 
vessels. Occasionally, communication is established with the large 
venous trunks, particularly the descending vena cava. Complete arrest 
or cure of an 'aneurysm may take place by organization of the clots 
contained, but such a result is rare. 




Fig. 241. — Dissecting aneurysm of the aorta: the aneurysm began near the aortic 
valves and extended to the iliac branches, converting the aorta into a double tube: a, 
Transverse section; b, longitudinal section. 

3. Dissecting aneurysm is most common in the aorta. As the 
result of degenerative lesions or of mechanical injury rupture of the 
intima occurs, and the blood finds its way between the coats of the 
artery, often burrowing to considerable distances. In a case under 
the observation of one of the authors the walls of the aorta were dis- 



542 



A TEXT-BOOK OF PATHOLOGY 



sected as far as the bifurcation, where secondary ruptures had occurred 
in the intima (Fig. 241). Usually the dissection takes place in the 
media, which is thus separated into two parts. Subsequently the ad- 
ventitious canal may become lined with endothelium, and in the case 
quoted atheromatous plates had formed in the latter. 

Associated Conditions in Other Parts. — Some hypertrophy of the 
heart may occur when an aneurysm is situated near the root of the 
aorta, and particularly in instances in which direct pressure is brought 
to bear upon the heart. As a rule, however, the amount of hyper- 
trophy is much less than might be expected. Pressure upon the venous 
channels is an early manifestation, and leads to passive congestion and 
often to dropsy and cyanosis. Necrosis of the parts which are directly 
compressed has already been alluded to. Portions of the clot within 
the aneurysmal cavity not rarely become separated, and are carried as 
emboli to the peripheral parts of the circulation. 

False or spurious aneurysms most commonly result from trauma- 
tism, though sometimes spontaneous rupture of the vessel is the imme- 
diate cause. The blood may find its way from the ruptured artery into 
the surrounding tissues, forming a blood-tumor, or hematoma, which 
becomes encapsulated by condensation of the surrounding tissues and 
by reactive overgrowth of connective tissue stimulated to activity by the 
fibrin formation and liberation of leukocytes. The retaining wall thus 
formed majr in some cases be lined with endothelial cells, and secondary 
inflammatory thickening or atheromatous plates may form. When an 
artery and vein are both injured, as is sometimes the case in phlebotomy, 
the blood may enter the vein and distend this markedly. The term 
aneurysmal varix is applied to such cases. In other instances the artery 
and vein communicate by an intermediate sac formed by the condensa- 
tion of the intervening tissues, and for such the name varicose aneurysm 
is used. 

The Veins 

Anatomical Considerations. — The veins resemble the arteries, 
excepting that the muscular coat is less well developed, and that most 
of the veins are supplied with endothelial reduplications or folds, which 
act as valves and prevent the backward flow of the blood. 

CIRCULATORY DISTURBANCES 

Thrombosis of the veins is the most important condition. This, 
however, has been sufficiently considered under Thrombosis (see p. 73). 

DEGENERATIONS 
Fatty degeneration of the intima and media may occur as in the 

arteries, but it is comparatively rare and unimportant- 
Calcification is met with in veins which have become dilated or 

varicose, or otherwise diseased. 

INFLAMMATION, OR PHLEBITIS 
Acute phlebitis is a comparatively common affection. It may 
occur as the result of inflammation, particularly of infectious nature, 
in the neighborhood of the vein. In such cases the outer coat is first 



DISEASES OF THE CIRCULATOKY SYSTEM 



543 



involved, and the term "periphlebitis " is properly applied. This 
condition is met with in association with infected wounds and phleg- 
monous inflammations of the subcutaneous tissues. The veins beneath 
the skin may be distinctly visible as blue streaks running in various 
directions. Microscopically, there is found to be an invasion of the 




Fig. 242. — Thrombophlebitis of the femoral vein (from a specimen in the Museum of the 

Philadelphia Hospital) . 

adventitia with round cells, and actual foci of suppuration are not un- 
common. The cellular infiltration may extend to the media and some- 
times to the intima, and not rarely thrombosis occurs within. The 
thrombi thus formed may secondarily become infected, soften, and 
occasion septic embolism. 




Fig. 243. — Phlebitis and periphlebitis of the umbilical vein of the newborn: purulent 
infiltration of the intima and adventitia; calcareous particles in the media (Birch-Hirsch- 
feld). 

When the exciting cause first makes itself felt within the lamen of 
the vessel, thrombosis is one of the earliest changes because slowness 
of the current together with whirls or eddys around valves favor coa- 
gulation; this is termed endo- or thrombophlebitis (Figs. 242 and 243). 
The histological changes are similar in these to those which occur in 



544 



A TEXT-BOOK OF PATHOLOGY 



thrombo-arteritis, and as terminal results localized thickening of the 
venous wall or irregular contractions by the formation of fibrous adhe- 
sions and even complete obliteration of the venous channel may result. 
When the thrombus is thus organized or partially organized calcification 
may eventually occur, and in this manner phleboliths, or vein-stones, are 
formed. 

Chronic phlebitis, or phlebosclerosis, corresponds to chronic 
arteritis or arteriosclerosis. A certain amount of chronic inflammatory 
thickening of the vein ensues as a consequence of thrombophlebitis. 
Phlebosclerosis may also be due to overdistention of a vein resulting 
from thrombosis or other forms of obstruction, and thus plays a secondary 
part in dilatation of the veins, or phlebectasia. 

Phlebosclerosis may, however, occur as a widespread affection in 
association with arteriosclerosis, though rarely in equal degree, in con- 
sequence of certain systemic conditions — syphilis, alcohol, gout, etc. 
The changes occurring in the vein are much the same as those in the 
artery, but the new-formed fibrous tissue in the intima less commonly 
undergoes degenerative changes and calcification than in arterial scle- 
rosis. Sections of the affected veins show, as a rule, absence of signs 
of inflammation and of marked degeneration. The essential change is a 
proliferation of the cells of the intima and of the connective tissue of 
the media. The condition resembles more a functional hyperplasia, the 
result of mechanical forces, than a chronic inflammation. 

In cases of congenital syphilis an interesting form of thickening of 
the intima, leading to stenosis or even complete obstruction, has been 
found in the veins of the umbilical cord, and less frequently in the 
portal vein. Similar hyperplastic endophlebitis has been found in the 
veins of the extremities in syphilis of adults. 

DILATATION OF THE VEINS; PHLEBECTASIA; VARICOSITY 

Etiology. — Dilatation of the veins occurs from mechanical obstruc- 
tion to the circulation or from weakness of their walls. It presents itself 
more commonly in dependent portions of the body, and is particularly 
frequent in the veins of the legs, of the rectum, of the neck of the bladder, 
of the spermatic cord, of the scrotum, and of the vagina. 

Mechanical causes are most important. Thus, in cases of cirrhosis 
of the liver, of obstinate constipation, and of pelvic tumors, dilatation of 
the veins of the rectum, causing hemorrhoids, is frequent. In cases of 
abdominal tumors, repeated pregnancy, or other causes of obstruction 
to the venous return of the blood from the lower extremities, varicosity 
of the veins of the legs is frequently observed. Always, however, local 
disease of the veins themselves tends to make the dilatations more 
pronounced, and, in addition, systemic depression and, particularly, car- 
diac weakness are contributing causes which operate by aiding in the 
stagnation of the blood, which otherwise might pass by collateral chan- 
nels to its proper destination. 

Pathological Anatomy. — -The veins in phlebectasia become dilated 
and also elongated, so that they soon assume a tortuous character. Not 
rarely masses of much-dilated veins lie closely aggregated in groups or 
clumps" beneath the surface of the skin; and, communications may be 



DISEASES OF THE CIRCULATORY SYSTEM 545 



established between the adjoining pouches of dilatation, and thus a 
cavernous tissue is formed. The walls of the dilated veins are usually 
considerably thickened (phlebosclerosis), and even calcification may 
occur in the intima. 

Results. — The circulation of the blood is slowed and thrombosis is, 
therefore, frequent. The thrombi may undergo organization or calci- 
fication, or in other cases may soften and occasion embolism. When 
varicosities are established in the veins of any submucous tissue, catar- 
rhal inflammation of the overlying mucosa is occasioned and generally 
proves obstinate. At the same time a certain amount of hyperplasia of 
the connective tissue between the dilated veins takes place and thicken- 
ing of the mucous membrane results. When the subcutaneous veins are 
involved the skin is prone to become thickened and to present eczema- 
tous inflammation, while the subcutaneous tissue may be greatly 
increased in thickness and density (phlebectatic elephantiasis or pachy- 
dermia). Not rarely ulcerations of the skin of the lower extremity owe 
their origin to varicosity of the veins, and such ulcers are prone to prove 
indolent and obstinate. Hemorrhage may occur from varicosities of the 
submucous veins, particularly in case of hemorrhoids and in the esopha- 
geal varicosities of drunkards. 

TUMORS 

Tumors rarely begin in the walls of the veins, though myoma and 
sarcoma have been described. More commonly the walls of the veins 
are secondarily involved in cases of tumors surrounding them. Aschoff 
lays stress upon the involvement of veins by leukemic infiltrates and 
myeloma. 

INFECTIOUS DISEASES 

Tuberculosis not rarely attacks the veins, particularly those of the 
lungs. Perforation of the wall may take place, and miliary tubercu- 
losis is a frequent consequence. 

Syphilis of the veins has already been referred to. 

The Lymphatic Channels 

Anatomical Considerations. — The lymphatic system begins in the 
lymph-spaces, which occupy spaces between the tissue elements in all 
parts of the body. These lymph-spaces unite to form definite lymphatic 
capillaries, which are channels having walls composed of a single layer 
of endothelial cells. The lymphatic capillaries unite to form larger 
vessels, and in these connective-tissue coats support the endothelial 
lining. The system is a closed one, there being no direct connection 
between it and the cells, any interchange occurring through the endothelia. 
Drainage is to lymph nodes, not to veins. 

Lymph coagulates very slowly — ten to twenty minutes — due to 
the small amount of thrombokinase in it. Intralymphatic thrombosis 
does occur after ligation, but it is much favored by destruction of tissue 
locally, such a condition freeing thrombokinase. Opie has shown this 
by addition of tissue extracts to freshly drawn lymph. Bacterial inva- 
sion of lymph-channels assists in freeing thrombokinase. 

35 



546 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATION 

Inflammation of the lymphatic vessels, or lymphangitis, is 

always secondary to inflammatory affections of the parts surrounding the 
lymphatics, or of those parts from which the lymphatics take their 
origin. In cases of infective lesions of the extremities, red lines, indi- 
cating the position and course of the inflamed lymphatics, may not in- 
frequently be seen beneath the skin, extending upward to the nearest 
lymphatic glands. Histologically, the first change in such cases is 
swelling and offtimes multiplication of the endothelial cells of the 
lymphatic vessel; later, there may be accumulation of leukocytes within, 
and the lymphatic channel may be uniformly filled with pus or dis- 
tended at different points. Usually a certain amount of perilymphangi- 
tis accompanies the process, and in cases of violent septic infection the 
surrounding tissues may become extensively involved in phlegmonous 
inflammation. Thrombosis may take place within the lymphatic channel 
in cases of moderate severity and thus obstruction ensue. The termina- 
tion is either in resolution or suppuration, with more or less widespread 
involvement of the surrounding tissues. Resolution may be only 
partial, the inflammatory changes going on to the formation of con- 
nective tissue, which may obliterate the channels, or the restitution of 
the wall of the lymphatic vessel may be imperfect and subsequent 
dilatation results. 

A primary chronic lymphangitis may arise from prolonged obstruc- 
tion to the lymph flow or by continued irritation, as by foreign particles 
which the channels are draining to the lymph-nodes. The vessels are 
changed to a solid band of endothelial cells surrounded by a thickened 
fibrous coat. 

DILATATION OF THE LYMPHATICS, OR LYMPHANGIECTASIA 

This condition may be an acquired or a congenital affection. 

Acquired dilatation of the lymphatics results from obstruction to 
the larger channels, as in cases of pressure upon or thrombosis of the 
thoracic duct, or of obstruction of the lymphatic channels by filariae. 
In other cases it is due to inflammations surrounding the lymphatics 
and leading to weakness of their walls. It is very commonly observed 
in the subcutaneous lymphatics, and constitutes the endemic elephan- 
tiasis of warmer countries. This condition is particularly common in 
the lower extremities, scrotum, and labia, but may affect other parts. 
The skin is greatly thickened and the surface often of irregularly lobu- 
lated character. On incision into it there is found an abundant exuda- 
tion from the subcutaneous tissue of serous or of milky liquid. 

Obstructive dilatation of the intra-abdominal lymphatics is not 
unusual. Rupture of dilated branches in the genito-urinary tract 
may lead to chyluria; similarly, chylous ascites or hydrothorax may 
arise by obstruction or rupture of the thoracic duct. 

Congenital lymphangiectasia may take the form of a diffuse condi- 
tion affecting the lymphatics more or less regularly in certain parts of 
the body, or it may appear in circumscribed areas, often in situations 
in which the ordinary lymphatic supply is not abundant. The diffuse 
form occasionally presents itself in the newborn in the form of edema- 



DISEASES OF THE CIKCULATORY SYSTEM 



547 



tous or semicystic swellings of the subcutaneous tissues, resembling those 
of elephantiasis. In the same group of cases belong the instances of con- 
genital enlargement of the tongue (macroglossia) and of the lips (macro- 
cheilia). In some of these instances the development of the condition 
does riot occur until sometime after birth, though the process is, in 
reality, congenital. Localized lymphatic dilatations constitute the form 
of new growth known as lymphangioma. (See General Pathology.) 

INFECTIOUS DISEASES 

Tuberculosis. — The lymphatics play an important part in the dis- 
semination of tuberculosis within the organs, and they may themselves 
be involved in the disease. This is beautifully illustrated in cases of 
intestinal tuberculosis with ulceration. In such cases the lymphatic 
channels in the serous coat may be seen radiating from a point opposite 
the ulceration toward the mesentery, and small miliary nodules are 
seen in their course. 

Syphilis. — The lymphatics may be involved in syphilitic processes 
in their vicinity, but the changes are not characteristic. 

TUMORS 

In addition to the lymphangiomata referred to, the lymphatic vessels 
are the primary seat of tumors resulting from multiplication of the 
lining endothelial cells, which are known as endotheliomata. These 
tumors are especially common in the serous surfaces, but may also be 
met with in the skin and elsewhere. The lymphatics bear an important 
relation to the metastasis of malignant tumors, particularly of carcino- 
mata. The carcinoma cells enter the lymphatics and are carried by 
the stream to distant parts of the body; sometimes the lymphatics near 
carcinomata are found densely packed with cancer cells. 

PARASITES 

The adult of the Filaria bancrofti resides in the lymphatic vessels, 
and the embryos may be present in large numbers. (See General 
Pathology.) 

THE THORACIC DUCT 

Pathological processes involving the thoracic duct resemble in 
general character those of the other lymphatic vessels, but the size of 
the duct and its anatomical relations make the diseases affecting it of. 
somewhat greater significance than the same diseases when occurring 
in the smaller lymphatics. 

Thrombosis may occur in association with inflammation of the duct 
or without such, and there may be permanent occlusion in consequence. 
Dilatation of the lower parts of the duct, as well as of the lymphatic 
vessels of the abdomen, may ensue, and sometimes the receptaculum 
or other portions of the duct may become cystic. Chylous ascites may 
likewise result. More commonly collateral circulation re-establishes 
communications and serious consequences are not observed. 

Dilatation of the thoracic duct may also result directly from cardiac 
failure with engorgement of the greater veins. The outflow of lymph 



548 



A TEXT-BOOK OF PATHOLOGY 



is impeded, and in some cases the backward pressure of the blood 
through the superior cava may fill and distend the upper part of the 
thoracic duct with blood. 

Inflammation occurs in consequence of various inflammatory dis- 
eases of the abdomen or of the pelvis, by the invasion of irritants through 
the lymph received from the affected areas. There may also be direct 
extension of inflammation in cases of abdominal disease, or in pleurisy 
or other intrathoracic affections. 

Tuberculosis affecting the abdominal portion of the duct is some- 
times observed in cases of intestinal or mesenteric tuberculosis, and 
may occasion secondary miliary tuberculosis, particularly the form in 
which the disease is subacute or chronic in its course (Weigert). It 
occurs in periductal or intimal form. In the latter case it may be either 
as a soft spreading lesion leading to erosion and ulceration, or as a poly- 
poid outgrowth into the lumen. 

Tumors. — Primary tumors (sarcoma, fibroma) are sometimes ob- 
served, and secondary carcinoma is more commonly met with. 



CHAPTER IV 



DISEASES OF THE RESPIRATORY SYSTEM 

THE NASAL CAVITIES 

Anatomical Considerations. — The mucous membrane of the nose 
is usually prominent, especially over the lower turbinated bone, where 
it is 4 mm. thick. In the lower or respiratory parts of the nose the 
epithelium is stratified, ciliated, columnar in type. The submucosa is 
replete with a venous network, giving it, particularly over the inferior 
turbinated bone, the appearance of erectile tissue. In the olfactory 
regions non-ciliated columnar cells, which become attenuated at the 
inner end, line the surface. Between the filiform prolongations within 
lie round and tapering olfactory cells. Small tubular and racemose serous 
and mucous glands are freely distributed in the mucosa. 

CONGENITAL ABNORMALITIES 

Deviations of the septum and other slight anomalies are common. 
Atresia, absence of the septum or other parts, or complete absence of 
the nose are rare defects. Harelip and cleft palate frequently involve 
the nasal cavities. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs in consequence of exposure to great heat 
or cold, or of ascending elevations, and when the heart is overstimulated. 
Certain odors or finely divided dust-particles may provoke transient 
congestion. Frequently, however, such congestion terminates in in- 
flammation. 

Passive hyperemia may be due to cardiac weakness, obstructive 
diseases of the lungs, and local pressure on veins. 

Hemorrhage.- — In either passive or active congestion and in inflam- 
mations of the mucous membrane hemorrhage (epistaxis) may occur. 
Bleeding may also result from blood-diseases (hemophilia, pernicious 
anemia, leukemia), from disease of the blood-vessels (arteriosclerosis), 
or in a paroxysmal form from obscure causes. Epistaxis is a frequent 
prodromal symptom of typhoid fever; less frequently it occurs in 
influenza and other infections. Trauma may cause nosebleed. It also 
may occur vicariously when normal menstruation fails. 

Edema of the mucous membrane may be associated with inflam- 
mation, in coryza, but perhaps just as important is the swelling occurring 
in persons susceptible to the action of pollens (hay fever) or emanations 
from animals, which is edematous before inflammation develops. 

549 



550 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Acute nasal catarrh (acute rhinitis, coryza) commonly results from 
exposure to cold. Irritant fumes may cause it; often it seems infectious 
and contagious. It may occur as an associated condition in various 
infections, as grip, typhoid fever, measles, etc. Hay-fever and its 
related disorders are forms of acute rhinitis. Gout and other nutri- 
tional disorders may predispose to rhinitis or cause it. The mucosa is at 
first intensely red and dry; then an irritating serous, followed by mucous 
and finally mucopurulent, exudation is discharged. Herpes or ecze- 
matous eruptions of the lips are common. Considerable inflammatory 
edema of the mucous membrane of the nose and accessory cavities may 
occur. It may spread to the middle ear, to adjacent sinuses, or to the 
brain. This is especially true in the purulent form. Pyemia of the 
antrum of Highmore may start in this way. 

Chronic rhinitis follows repeated acute attacks, especially in 
tuberculous or syphilitic persons. The mucosa, especially over the 
inferior turbinated bone, becomes thickened {hypertrophic rhinitis) 
and may remain so, or undergo atrophy (rhinitis atrophica). In the 
atrophic form the exudate is scanty and appears as dry, greenish crusts, 
which sometimes occasion extensive ulcerations and become horribly 
offensive. To such cases the term ozena is applied. Various forms of 
bacilli and micrococci have been discovered, the most frequent being an 
organism resembling the bacillus of Friedlander, which is considered the 
cause of the disease by many observers. Fetid discharges may also 
occur in syphilitic or tuberculous diseases of the nose (ozcena syphilitica 
seu tuberculosa). 

In the hypertrophic variety the openings of the sinuses about the 
nose may be slowly closed, with resultant chronic inflammation, which 
may lead to widespread phlegmon or necrosis. In this form there is 
increase of the submucosa and but little change in the epithelial layer, 
except for occasional glandular distention or distortion of mucous glands. 
While secondary atrophy may occur, what is called atrophic rhinitis 
(as above described) is said by some to be atrophic from the start, there 
being atrophy of both glands and supporting tissue. 

INFECTIOUS DISEASES 

Diphtheritic rhinitis is usually secondary to pharyngeal diphtheria. 
Primary diphtheritic rhinitis of rather benign character is occasionally 
observed. Non-specific pseudomembranous rhinitis is a very rare con- 
dition. 

Syphilis in the secondary stage and in congenital cases sometimes 
occasions simple catarrhal rhinitis. Mucous patches may occur, or 
gummata spring from the mucous membrane or from the periosteum 
or perichondrium. The latter tend to ulcerate and cause destruction. 
The purulent discharge may be fetid. 

Tuberculosis may occur as disseminated or aggregated tubercles 
of the mucous membrane, or as ulcers and carious processes. These 
are all rare, but "scrofulous catarrhs" of children, probably often due to 
tuberculous lesions, are common. Lupus of the face may extend to the 
nose. 



DISEASES OF THE RESPIRATORY SYSTEM 



551 



Glanders occasions intense purulent and hemorrhagic rhinitis, or 
nodular growths with ulceration. Nodules and ulcers are common in 
leprosy. Irregular swelling and induration of the mucous membrane of 
the nose and the adjoining skin in rhino scleroma are rare conditions. 

TUMORS 

The commonest form of tumor is the polyp, which is sometimes 
distinctly the result of hypertrophic rhinitis, at other times obscure in 
origin. Polypi present the ordinary structure of the nasal mucosa, 
with a tendency to cystic change from occlusion of the glands, or to 
adenomatous appearances from proliferation of the glandular elements. 
Fibroid, myxomatous, and sarcomatous polypi also occur. In all cases 
there is a tendency to recurrence after removal. A rare form of hairy 
polyp has been described. Chondromata, osteomata, sarcomata, and 
epithelial or glandular cancers may be found. 

PARASITES AND FOREIGN BODIES 

Larvae of various flies may occur in the nasal chambers and set up 
serious inflammatory lesions. Foreign bodies may become incrusted 
with lime-salts and lead to the formation of rhinoliths. These formations 
may also arise around a nucleus of epithelial crusts, mucus, or desqua- 
mated epithelia in obscure niches of the nasal cavity after prolonged 
catarrh. 

The sinuses (frontal, ethmoid, and sphenoid) and the antrum of 
Highmore are frequently involved in inflammations of the nasal mucosa, 
and when their outlets are obstructed by swelling of the nasal mucosa 
chronic lesions (catarrhal or suppurative) may occur. These may occa- 
sion generalized infections or infectious toxemias of various forms. 
Empyemata of the sinuses may open into the nose, the cranial cavity, 
the mouth, or may discharge externally. Chronic enlargements of the 
lymphadenoid tissue behind the nose are discussed on page 634. 

The Larynx 

Anatomical Considerations. — The lining epithelium of the larynx 
is stratified squamous as far as the false vocal cords. Below these and 
throughout the ventricles it is stratified, ciliated, columnar, and thus 
continues into the trachea and bronchi, excepting over the true vocal 
cords, which are covered with stratified squamous epithelium. The 
tunica propria contains much yellow elastic fiber, and the submucosa is 
quite loose, especially over the base of the epiglottis and the aryepi- 
glottic folds. 

CONGENITAL ABNORMALITIES 

Minor defects in shape of the constituent parts of the larynx are not 
rare. Congenital fistulae communicating with the exterior, and dilata- 
tion of the ventricles similar to the normal pouching found in certain 
monkeys, due to imperfect closure of one of the branchial arches, are 
occasionally met with. Abnormal largeness and smallness, the latter 
especially in persons having poorly developed sexual organs and those 
castrated early in life, are more frequent conditions. 



552 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Anemia may occur in general anemia, and is sometimes found in 
tuberculous and chlorotic subjects in pronounced degrees. 

Active hyperemia follows exposure, overuse of the voice, and irri- 
tation by gases, dust, and the like. 

Passive hyperemia occurs in heart diseases, intrathoracic tumor, and 
other conditions obstructing the venous circulation. In active conges- 
tion the larynx is bright red ; in passive congestion it is dark red in color, 
and distended veins may be prominent. 

Hemorrhages are seen in the mucosa after death from asphyxia, 
in cases of purpura or other hemorrhagic conditions, as well as in intense 
inflammation of the larynx. Large hemorrhages may occur in cases of 
cancer. 

Edema of the epiglottis, the aryepiglottic folds, and other parts of 
the larynx may be part of anasarca in Bright 's disease or heart dis- 
ease, or may result from local pressure upon the veins; in any case the 
swelling may exaggerate if the head be bent enough, in sleep or un- 
consciousness, to interfere with circulation. The parts become greatly 
swollen and of an anemic, translucent appearance. Non-inflammatory 
edema may not be visible after death but the mucosa is loose and wrin- 
kled. Great stenosis of the larynx commonly results. Generally 
"edema of the larynx" is inflammatory in nature (see below). 

INFLAMMATIONS 

Acute catarrhal laryngitis results from chemical or mechanical 
irritation; it accompanies whooping-cough, measles, small-pox, typhoid 
fever, and other infections. The mucous membrane is bright red and 
swollen. A scanty mucous or mucopurulent exudate is usually noted. 
Intense laryngitis is attended with small hemorrhagic ecchymoses or 
erosions; true ulcers are rare. Follicular ulcers are sometimes seen, and 
rarely small vesicles arise upon the surface (herpetic laryngitis) . 

As is the case with all surface inflammations, laryngitis may assume 
a catarrhal, fibrinous, pseudomembranous, purulent, or ulcerative form. 
They merge into one another and, with the exception of the specific 
forms, have no peculiar etiology or pathology. 

Pathological Physiology. — Acute laryngitis may cause considerable 
disturbance of breathing by the swelling of the mucous membrane, and 
in children often leads to spasmodic contraction of the laryngeal muscles, 
with paroxysmal dyspnea (Jalse croup). 

Chronic catarrhal laryngitis may follow the acute form or begin 
gradually. Overuse of the voice and exposure to cold or irritating 
gases or dust are the common causes. The mucous membrane is usually 
thickened and somewhat granular or even papillomatous and, except 
where the epithelium has changed to squamous type, there is a thick 
closely adhering muco-purulent exudate. There is a tendency for the 
epithelium to assume a squamous or epidermoid character (pachydermia 
laryngis). In the later stages atrophic changes may ensue. Fibrous 
thickening and stenosis of the larynx sometimes result from the chronic 
irritation of foreign bodies, such asjntubation tubes. 



DISEASES OF THE RESPIRATORY SYSTEM 



553 



Edematous laryngitis is generally known as edema of the larynx. 
Nearly always it is a true inflammatory edema, due to violent irrita- 
tion, general or local infection, or severe local lesions of a chronic nature, 
such as tuberculous or syphilitic ulceration and perichondritis; it is also 
seen in angioneurotic edema. The looser submucous tissues at the 
base of the epiglottis and over the aryepiglottic folds become greatly 
swollen, and the surface is more or less translucent. Sometimes the 
edematous infiltration is yellowish, or even quite purulent, especially 
in cases in which phlegmonous suppurations have extended from neigh- 
boring parts (retropharyngeal abscess, erysipelas). When circumscribed 
areas are affected abscess results. 

Perichondritis, inflammation of the perichondrium of the cartilages 
of the larynx, is usually secondary to serious laryngeal diseases, as 
syphilitic or tuberculous ulcers, car- 
cinoma, etc. It may be primary in 
typhoid fever or other infections. 
Frequently suppuration and necrosis 
of the cartilage result, but merely 
localized induration and swelling may 



occur. 



INFECTIOUS DISEASES 



Diphtheritic and croupous in= 
flammations may be part of the 
anatomical changes in diphtheria, but 
may also occur in typhoid fever, scarlet 
fever, small-pox, or other infectious 
diseases (due in such cases to strepto- 
cocci or other organisms), or from 
violent irritation by steam or the like. 
The surface of the larynx is covered 
with a more or less adherent grayish 
or yellowish pseudomembrane, which 
consists of a network or masses of 
fibrin entangling degenerated round 
cells and epithelium. The membrane 
is most adherent where the epithelium 
is squamous. Diphtheritic laryngitis 
usually follows a similar process in the 
pharynx. (See Diphtheria and Pseu- 
domembranous Inflammation, Part I, 
page 135.) 

Tuberculosis is nearly always secondary to pulmonary tubercu- 
losis; primary lesions are exceedingly rare. Small localized tuberculous 
masses or more dhiuse tuberculous infiltration are found in the mucosa 
and submucosa, especially on the posterior wall of the larynx, and may 
remain for long periods as the infiltrative type, but caseation and ul- 
ceration are usually early developments (Fig. 244). There is no reason 
to divide the tuberculous lesions in the larynx into different forms, as 
they do not have peculiar courses. Simple catarrhal inflammation or 




Fig. 244. — Tuberculous erosion and 
ulceration of the larynx, causing extensive 
destruction of the vocal cords (from a 
specimen in the Museum of the Phila- 
delphia Hospital) . 



554 



A TEXT-BOOK OF PATHOLOGY 



hypertrophic conditions of the mucous membrane between the tubercu- 
lous masses, giving rise to warty or polypoid growths or edematous 
laryngitis and perichondritis, may complicate the tuberculous lesions. 
Lupus of the nose and pharynx may extend to the larynx, where it 
occasions nodular thickenings and ulceration. Primary laryngeal lupus 
has been observed. 

Syphilis may occasion simple catarrh of the larynx, mucous patches, 
or infiltration and erosion of the mucous membrane secondary to 
pharyngeal involvement. The latter conditions are most frequent in the 
epiglottis, the posterior wall of the larynx, and the vocal cords. Gum- 
mata may occur in the same situations independent of pharyngeal 
syphilis, and lead to deeper ulcers. In the healing of syphilitic ulcers 
irregular papillomatous elevations of the healthy mucosa or extreme 
contractions and deformities of the larynx may occur. 

Lepra and glanders sometimes occur in the form of nodular swell- 
ings and ulcers. 

Swelling and ulceration of the lymphatic follicles, chiefly at the 
base and side of the epiglottis, analogous to the lesions in the intes- 
tines, may occur in typhoid fever; and in small-pox there may be small 
areas of infiltration and epithelial degeneration, 
or even pseudomembranes. 

Atrophy of the mucous membranes with 
various degenerative changes or deposits may 
occur in the larynx as the result of chronic 
inflammation in loco, or as a part of a con- 
stitutional disease (gout, rheumatism). 

Stenosis is due to pressure from without or 
by contraction of healed ulcers. 



TUMORS 

Papilloma. — Over one-half of all tumors of 
the larynx belong to the group of papillomata 
or papillomatous fibromata. These are simply 
hypertrophied papillae covered with a thick mantle 
of squamous epithelium (Fig. 245) . The stroma 
may be insignificant and the epithelium consider- 
able (hard papilloma), or the stroma may be 
excessive, highly vascular, and infiltrated with 
round cells, while the epithelial covering is thin 
(soft papilloma) . Papillomata are most frequent 
on the false vocal cords or on the other parts 
of the larynx lined with squamous epithelium. They usually occur 
in numbers, but may be solitary. Chronic inflammation often de- 
termines their occurrence, and they are not infrequent around chronic 
ulcers or carcinoma of the larynx. Simple hyperplasia of mucous mem- 
brane, of normal structure, occurs in various chronic inflammatory 
conditions of the larynx. 

Fibroma. — Nodular, sessile, or polypoid fibromata constitute one- 
third of all tumors. They are most frequent on the vocal cords and in the 
upper part of the larynx. 



Fig. 245. — Papillomata 
of the vocal cords (from a 
specimen in the Museum of 
the Philadelphia Hospital) . 



DISEASES OF THE RESPIRATORY SYSTEM 



555 



Cystic dilatation of the glands may occasion mucous polypi. 
Adenoma, lipoma, myxoma, sarcoma, and chondroma are rare tumors. 
Tumor-like masses of heterotopic thyroid-gland tissue have been found 
in the larynx. 

Carcinoma may be primary or, less frequently, secondary. Pri- 
mary carcinoma is usually of the squamous variety and occurs about 
the vocal cords. Nodular thickening with ulceration results. Papillo- 
matous thickening* of the mucous membrane frequently surrounds the 
growth. Secondary involvement of the cervical glands and esophagus 
may occur. 

Of 1100 tumors of the larynx collected byBruns, 602 were papillomata; 
346, fibromata; 73, mucous polyps; and 27, cysts; 76 per cent, occupied 
the true cords or the anterior commissure of the cords. Mackenzie 
found 67 per cent, papillomata and 16 per cent, fibromata. Cysts 
of the epiglottis occur, mostly on the anterior surface next to the tongue, 
by occlusion of the ducts. One case seen lately had acquired the size 
of an English walnut. Similar formations within the laryngeal cavity 
have been seen. 

PARASITES AND FOREIGN BODIES 

The larval Trichinella spiralis may infest the laryngeal muscles; 
and lumbricoids occasionally enter from the pharynx. Echinococcus 
cysts are very rare. 

Large foreign bodies may cause death by suffocation. Smaller 
bodies may rest in the larynx, especially the ventricles, for years, be- 
coming surrounded by hyperplastic mucous membrane or a capsule 
of fibrous tissue. Calcareous concretions may form around small 
foreign bodies or spontaneously in the ventricles. 

THE TRACHEA 

MALFORMATIONS 

Congenital Malformations. — Complete absence of the trachea oc- 
curs in acephalic monsters. Congenital decrease in length or diameter, in 
the number or completeness of the cartilages, and similar minor deform- 
ities are more common. An adventitious bronchus is occasionally seen, 
especially on the right side, and fistulous communications with the 
exterior or with the esophagus are rare congental defects. Diverticula 
may be due to a rudimentary condition of a supernumerary bronchus. 
Congenital cysts may occur between the trachea and esophagus when 
fistulous communications between them become closed at either end. 

Acquired Malformations. — Dilatations of the trachea may be 
diffuse br localized. They depend for their occurrence upon weakness of 
the walls and some impediment to expiration. Saccular dilatations are 
usually on the posterior wall. Narrowing of the lumen may be due to 
pressure of tumors or aneurysms, to new growths or cicatricial contrac- 
tions (especially syphilitic), or to foreign bodies within. 

CIRCULATORY DISTURBANCES 

Anemia and active and passive congestion result from the same 
causes as in the larynx, and the pathological anatomy is the same. 



556 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Inflammations are usually associated with laryngitis or bronchitis, 
and are due to the same causes. Simple catarrhal and pseudomem- 
branous inflammations are met with. Foreign bodies may cause exten- 
sive and deep inflammation, leading to ulceration and sometimes per- 
foration. Chronic inflammation assumes a proliferative and, later, an 
atrophic character. Proliferative (polypoid) inflammation is not infre- 
quent after tracheotomy, and may occasion serious obstruction. Ozena 
of the larynx and trachea may be associated with nasal ozena. 

INFECTIOUS DISEASES 

Tuberculosis and syphilis occur under the same circumstances as 
in the larynx. Syphilis may, however, affect the trachea and bronchi 
independent of disease of the pharynx or larynx. 

TUMORS 

Primary tumors are rare. Secondary involvement by cancer, ex- 
tending from the esophagus or thyroid gland, or by sarcoma, from the 
surrounding lymphatic structures or thymus gland, is more frequent. 
Ecchondroses and osteomata may spring from the cartilages, and 
multiple chrondromata have been found in the mucous membrane. 
Retention-cysts of the mucous glands are occasionally seen on the 
posterior wall, protruding outside the trachea. 

THE BRONCHI 

Anatomical Considerations. — The larger bronchi correspond very 
closely to the trachea in structure. The smaller divisons have thinner 
walls, being less provided with cartilaginous rings, but having instead 
small cartilage-plates and a greater abundance of muscle-fibers. The 
tubes having a diameter less than 1 mm. are called the terminal bron- 
chioles, and lead into yet smaller tubes, the alveolar passages, which open 
into dilated injundibula, and the last named are finally surrounded by 
air-sacs. The lining epithelium is stratified columnar, ciliated down to 
the terminal bronchioles where it becomes simple columnar. In the 
alveolar passages there is first polygonal, then flat, epithelium, while 
in the infundibula and air-sacs there are practically only flat epithelial 
cells. 

CONGENITAL MALFORMATIONS 

These are rare and unimportant. Dilatations or narrowing and 
anomalous division of the tubes have been noted. (See Trachea.) 

CIRCULATORY DISTURBANCES 

Anemia and hyperemia occur under the same circumstances as in 
the trachea and larynx. 

Hemorrhage. — Intense congestion may occasion hemorrhages into 
the mucous membrane or into the bronchi themselves. More fre- 



DISEASES OF THE RESPIRATORY SYSTEM 



557 



quently hemorrhage is due to catarrhal inflammation, tuberculous 
ulceration, or a general hemorrhagic tendency. Aneurysms of the 
aorta (see Fig. 240) and the small aneurysms of the pulmonary arterioles 
in tuberculosis of the lungs not infrequently rupture through the 
bronchi. 

INFLAMMATIONS 

Both acute and chronic bronchitis are common conditions, and there 
are several forms. 

Acute catarrhal bronchitis results from exposure, from inhalation 
of irritating gases, and from downward extension of tracheal catarrhs. 
The terminal bronchioles are frequently affected secondarily in pul- 
monary diseases. Bronchitis is constantly associated with some of the 
infectious fevers — typhoid fever, measles, whooping-cough, etc. Various 
micro-organisms have been found in bronchitis. Among these are the 
pyogenic micrococci, the diplococcus of Frankel, the bacillus of Fried- 
lander, the Bacillus influenzal, the B. coli, with many others. The 
mucous membrane presents an intensely red color; at first it is dry, 
but later a mucous or mucopurulent exudate is formed (see Fig. 34). 
The exudation may be excessive in quantity, in which case the condition 
is called bronchorrhea. This may be serous or purulent, and is sometimes 
very offensive in odor (fetid bronchitis). 

Accordingly, as the exudate assumes a serous, mucous or mucopuru- 
lent, or fibrinous character, these names are applied. They have no 
etiological significance aside from the specific infections. All forms may 
go over into gangrenous bronchitis by retention and putrefaction of 
exudate. 

Microscopically, the bronchial mucous membrane is infiltrated with 
round cells, especially in the purulent cases; the epithelial cells are de- 
generated, many being converted into goblet-cells; and the mucous 
glands are distended with mucus. The mucosa of the bronchi is covered 
with mucopurulent material containing degenerated epithelial cells and 
detritus. If the process proceed toward the respiratory alveoli, therefore 
into bronchi with progressively more delicate walls, the tissue about the 
air tube is almost always the seat of some round cell infiltration, while if 
the lesion be severe the adjacent alveoli may be involved in broncho- 
pneumonia. There has been described, as "capillary bronchitis a form 
limited to the smallest bronchi but it is questionable if this be a condition 
sui generis; it is much more likely to be a form of pneumonia. In all 
long standing bronchitides there is a peribronchitis. 

Pathological Physiology. — Bronchitis may occasion no other dis- 
turbance than cough. In many cases, however, the infection may cause 
fever and general depression. Substernal soreness or pain is not infre- 
quent, while generalized thoracic pain may result from the violent 
coughing. Dyspnea is rare excepting in children and old persons, in 
whom cardiac weakness and spasmodic contractions of the bronchi 
seem to be operative. 

Chronic catarrhal bronchitis occurs after repeated attacks of the 
acute form, and especially in old persons or in those who have some 
cardiac weakness which tends to cause congestion of the bronchi. Gout 



558 



A TEXT-BOOK OF PATHOLOGY 



seems to constitute a distinctly predisposing cause. Chronic bronchitis 
is frequently associated with chronic diseases of the lungs. In chronic 
cases the mucous membrane may undergo considerable alteration. Fre- 
quently the ciliated cells disappear entirely and are replaced by columnar 
or polygonal epithelium; and hypertrophic conditions of the mucous 
membrane are sometimes present. More frequently the bronchus is 
uniformly thickened by cellular infiltration and overgrowth of fibrous 
tissue. It may, indeed, become hypertrophic, and, when the overgrowth 
encroaches upon the lumen with progressive granulation tissue, an ob- 
literating bronchitis occurs. At times the mucosa may become atrophic, 
under which conditions it is dry, irregular and covered with scanty 
thick mucus. In the productive form the exudate may be profuse and 
fetid. The peribronchial tissue is almost always involved in fibrous 

inflammation. All these processes 
tend to weaken the wall predisposing 
to bronchiectasis. 

Fibrinous bronchitis occurs un- 
der a varfety of conditions. It is 
most frequent in association with 
laryngeal and tracheal diphtheria, but 
may also be due to inhalation of pow- 
erful irritants. Fibrinous inflamma- 
tion of the finer bronchi occurs in both 
croupous and catarrhal pneumonia. 
Finally, there is a form of chronic 
or essential fibrinous bronchitis, char- 
acterized by periodic attacks, in which 
fibrinous casts of the bronchi are 
formed and discharged (Fig. 246). 
In all forms of fibrinous bronchitis 
there are often found in the sputa, on 
microscopical examination, fine spirals 
wound about a central fiber (Cursch- 
mann's spirals); and within these or associated with them the small 
octahedral crystals described by Charcot and Ley den (Plate 10, Fig. 1). 

Bronchiolitis Exudativa. — This term was given by Curschmann 
to the condition of the terminal bronchioles he assumed to be present in 
cases of asthma. The sputa contain the spirals that bear his name and 
Charcot-Leyden crystals. The sputa in these cases are further char- 
acterized by the abundance of eosinophile cells (Plate 10). 

Ulcers of the bronchi are met with in severe catarrhal inflammations, 
but more frequently are tuberculous, syphilitic, or due to extension of 
ulcerative processes from neighboring parts. It is not unusual to find 
ulceration in the main bronchus opposite the point of pressure of an 
aneurysm. 

Peribronchitis may occur from direct extension of inflammation from 
within, or it may be due to extension along the lymphatic channels from 
the pleura or interlobular septa of the lung. It is practically constant 
in influenzae pneumonitis and commonly as a part of pulmonary tubercu- 
losis, and may be fibrous, caseous, or purulent. 




Fig. 246. — Large bronchial coagulum 
chronic fibrinous bronchitis ( Vierordt) . 



PLATE 10 




Fig. 2. — Sputum from a case of asthma, showing leukocytes, some containing eosino- 
phil granules, free eosinophile granules, and micrococci: stained with eosin and meth- 
ylene-blue (Jakob). 



DISEASES OF THE RESPIRATORY SYSTEM 



559 



STENOSIS AND OBSTRUCTION OF THE BRONCHI 

The smaller bronchial tubes may be considerably occluded by 
catarrhal swelling of the mucosa and accumulation of exudate within. 
Clinically, this is often so marked in bronchitis affecting the terminal 
bronchioles as to have suggested the name "suffocative catarrh." (This 
capillary bronchitis is always merely a part of bronchopneumonia, and 
will be considered under that head.) More serious obstructions of the 
bronchi occur when old ulcers have healed, leaving cicatrices; or in 
cases of tumors of the bronchi or pressure upon the outside. If the ob- 
struction be total and permanent, atalectasis of the lung occurs in that 
part supplied by the affected tubes. In temporary obstruction a mild 
local emphysema occurs beyond the obstruction. Foreign bodies are 
usually coughed up, but may remain for long periods and occasion 
obstruction. 

BRONCHIECTASIS, OR DILATATION OF THE BRONCHI 

This is due to increased pressure within the bronchi or to some 
weakness of the walls, or to both, when the fault lies primarily in the 
bronchial walls. If these be badly damaged, simply the force of the 
inspired air may suffice to cause dilatation, but the increased 
expiratory efforts of coughing may aid materially. When a part of the 
lung is collapsed (atelectasis) the impediment to the entrance of air leads 
to dilatations of the bronchi above the collapsed area. This is especially 
noted in children. The weight of accumulating secretions in the tubes is 
an occasional cause of bronchiectasis. Finally, in fibrous pneumonia the 
traction of the connective tissue, attaching itself, on the one hand, to the 
outer wall of the bronchus, and, on the other hand, to the pleura, may 
bring about considerable dilatations. 

An analysis of series of cases shows that chronic bronchitis and 
chronic cough stand at the head of the etiological antecedents. Probably 
in a much larger proportion of cases than is now recognized there is an 
association of bronchial dilatation with chronic bronchitis. 

The role played by such a process will be evident upon considering 
the loss of support to the tube by inflammatory destructions of its 
musculature and cartilage. To this must be added the effect of peri- 
bronchitis upon supporting aveolar and pulmonary tissue. Both these 
processes are well exemplified in influenza (q. v.) and in tuberculosis; in 
the latter instance cavitation by destruction of alveoli aids materially 
in allowing bronchi to distend. The clinician and pathologist also have 
in the past given little attention to cases in which the dilatations were 
not pronounced or saccular. Clinically, there can, however, be recognized 
a group of cases of chronic bronchitis with excessive sputa in which the 
bronchi are probably uniformly though slightly dilated. 

Among the other causes tabulated are preceding pneumonia, pleurisy, 
tumor, foreign body in the bronchus, aneurysm. 

A congenital varicose dilatation of bronchi is sometimes seen, due 
either to a malformation wherein no connection exists with the main 
bronchus, or to an inherent weakness of the wall, distention of the 
lumen arising with the first inspiratory actions. 



560 



A TEXT-BOOK OF PATHOLOGY 



The enlargement of the bronchus may be localized, when it is termed 
saccular bronchiectasis; or more uniform, when the names cylindrical 
and Jusijorm are applied, according to the shape of the bronchus (Fig. 
247). The latter types are frequently generalized and give symptoms 
only of chronic bronchitis. The results of saccular dilatation depend 
somewhat upon their size and position. If the swelling be small and can 
empty itself readily, few or no evidences of its presence will exist, but if 
the opening into the bronchus be small or if the cavity be dependent, 
secretions may accumulate and progressive distention occur. In these 
cases, emptying of the cavity has to be done by having the patient 
adopt a position which will make the secretion flow out of the sac. The 
mucous membrane may be almost nor- 
mal in appearance in small dilatations, 
but more commonly is thickened and 
irregular on the surface. There may 
even be actual polypoid outgrowths, and 
ulcerations may occur when the secretions 
are specially abundant and irritating. 
Microscopically, the epithelium is found 
to approach the squamous type; the 
wall of the bronchus is generally in- 
filtrated and cirrhotic. The exudation 
is generally purulent and copious, and 
may be very fetid. Occasionally it is 
thick and cheesy. 






Fig. 247. — Bronchiectasis: a, Saccular; b, 
lindrical; one-half natural size (Orth). 



cy- Fig. 248. — Honey-comb lung, illustrat- 
ing the extreme results of generalized 
acute bronchiolectasis of the bronchitic 
type (H. Morley Fletcher's case). 



Bronchiolectasis. — Cases of extensive dilatation of the small 
bronchi and bronchioles have been observed. They are especially com- 
mon in childhood and may be of a bronchitic type when bronchitis is 
the precedent condition, and an obscure pneumonic form in which the 
bronchiolar dilatation is associated with pneumonic consolidation. 
Bronchiolitis may be acute or chronic in its course and localized or 
quite general. In some cases the lung is quite honey-combed in appear- 
ance (Fig. 248). 



DISEASES OF THE RESPIRATORY SYSTEM 



561 



INFECTIOUS DISEASES 

Tuberculosis of the bronchi is usually associated with pulmonary 
tuberculosis, and appears in the form of miliary or larger nodules 
in the mucosa or submucosa, which tend to break down to form ulcers. 

Syphilis sometimes occurs in the form of eruptions and ulcers. There 
may be dense scar formation and deformity in consequence of the heal- 
ing of such ulcers. 

TUMORS 

Polypoid conditions of the mucosa occur in cases of chronic bronchi- 
tis. Fibroma, chondroma, and lipoma are rare forms of tumors. Pri- 
mary cancers may spring from the mucous glands or from the surface 
epithelium, but are very rare. Leukemic nodules are seen in the bronchi 
at times, and lymphosarcomata are not rarely found to spring from the 
peribronchial lymphatic tissues. 

PARASITES AND FOREIGN BODIES 

Bronchiectatic cavities may contain a growth of aspergillus — 
mycosis aspergillina. Round worms may enter by migration, and 
hydatid cysts are met with. The Paragonimus ringeri is a rare parasite 
invading the bronchi. 

Foreign bodies from the exterior usually enter the right bronchus. 
They often lead to atalectasis and inflammation unless they are coughed 
up. Bronchial concretions sometimes form by inspissation of the 
secretions, especially in bronchiectatic cavities. Very rarely cartilag- 
inous or bony masses, derived by outgrowth and later separation from 
the bronchial cartilages, are observed. 

The Lungs 

Anatomical Considerations. — The structure of the lungs in their 
unexpanded condition is very similar to that of an epithelial gland, 
consisting of ducts, the bronchi, and glandular tissue, the pulmonary 
parenchyma. The terminal bronchioles divide into several alveolar 
passages, which open into infundibula, and these, in turn, are surrounded 
by air-sacs. The groups of infundibula connected with a terminal bron- 
chiole constitute an acinus. Neighboring acini unite to form lobules, 
and the lobules unite to form lobes. The epithelial lining cells of the air- 
sacs are large flat plates, which resemble endothelial cells very closely. 
Beneath these cells is a layer of elastic tissue, which gives the lungs 
their characteristic elasticity, and in which is embedded a rich net- 
work of capillaries, that carry on the proper respiratory function of 
the lungs. These capillaries nre the terminal ends of the pulmonary 
artery. Another set of blood-vessels, the bronchial arteries, serve only 
to nourish the walls of the bronchi and the structure of the lungs them- 
' selves. The return circulation is mainly carried on by the pulmonary 
veins, which receive the blood of the pulmonary arteries and much of 
that of the bronchial arteries. The distribution of the lymphatic ves- 
sels in the lungs is of the greatest significance in pathological anatomy, 
especially with regard to the dissemination of infectious diseases in the 

36 



562 



A TEXT-BOOK OF PATHOLOGY 



lung itself. One system of lymphatics begins in the lymph-spaces be- 
tween the cells of the intervesicular septa. These lymph-spaces deliver 
their contents to lymphatic capillaries in the same region, and these, in 
turn, follow the alveolar passages, surrounding the latter on all sides. 
Where the several alveolar passages unite to form a terminal bronchiole 
the smaller lymphatic capillaries also unite to form larger branches, 
which follow the bronchioles. Other lymphatic vessels surround the 
pulmonary veins, constituting a perivascular system. Still another 
system begins in small subpleural capillaries, which unite, enlarge, and 
then penetrate the lung along the interlobular septa. Some, of them, 
however, pass at once to the peribronchial and peri vesicular tissues. All 
the lymphatic trunks leave the lung at the root and eventually discharge 
into the thoracic duct. 

Collections of lymphoid cells are found in various places along the 
lymphatics in the tissue of the lung. Near the root these are of consid- 
erable size, and merit the name of lymphatic nodes or glands. Still 
larger and more important ones are found surrounding the bronchi just 
outside the lungs and around the end of the trachea. This compound 
group of nodes is important as being the seat of hyperplasia in all acute 
inflammations of the lungs and in being involved to more or less extent 
in chronic processes. They frequently contain old healed or calcined 
tubercles and they are, in city dwellers at least, not uncommonly dark 
by their content of coal dust. They form therefore a barrier, for the blood, 
against particles received in the lungs. Occasionally they are involved 
in tumor formations. Suppuration is observed at times and this has 
been known to rupture into the bronchi. 

CONGENITAL DEFECTS 

Complete absence of the lungs has been noted in certain monsters. 
One lung may be absent, or its parenchyma may be undeveloped 
while the bronchi are dilated even to a cystic condition. The opposite 
lung is compensatorily enlarged. Minor abnormalities in the division 
of the lobes and the like are not rare; and in a few instances accessory 
lobes, wholly disconnected from the rest of the lung, have been observed. 

CIRCULATORY DISTURBANCES 

Anemia of the lung occurs as a part of general anemia, from pres- 
sure upon the lung, or from obstruction or obliteration of the blood- 
vessels. The last is the cause fo the great pulmonary anemia in 
emphysema of the lungs. The lungs are pale in color or of a mottled 
appearance in elderly persons, in whose organs considerable pigment is 
usually present. The apex is the first part to show anemia. 

Active Hyperemia or Congestion. — Exercise constantly leads to in- 
creased flow of blood to the lungs, and this may be extreme, causing rapid 
death (apoplexia pulmonum vascularis). In cases of irritation of the 
lungs by the inhalation of heated or cold air, or of irritating gases, and 
in certain lesions of the base of the brain there may be more or less 
active congestion of the lungs (Fig. 249). Collateral hyperemia occurs 
when the opposite lung or some other part of the body becomes anemic 
through a stoppage of the circulation in that part. The lung in active 



DISEASES OF THE RESPIRATORY SYSTEM 



563 



hyperemia has a dark-red color, and on section blood flows from the 
surface of section. The alveoli may contain free blood, and in marked 
cases there is blood in the sputa during life. 




Fig. 249. — Acute congestion of the lung (Karg and Schmorl). 

Passive hyperemia is, for the most part, a chronic condition due to 
causes which prevent the outflow of blood from the lungs. The most 
frequent cause is valvular disease, particularly mitral stenosis and re- 




Fig. 250. — Lung in chronic passive congestion showing thickened septa, round cell increase, 
heart-failure cells and coarsely granular coal pigment. 

gurgitation; but weakness of the left ventricle from fatty disease or 
fibroid degeneration acts in a similar manner. Any local cause of hin- 
drance to the outflow of the blood in the veins leads to similar passive 



564 



A TEXT-BOOK OF PATHOLOGY 



congestion. It is often found in the dependent parts of the lungs in 
cases of great asthenia, as in typhoid fever, when the respiratory 
movements are ineffectual in properly emptying the pulmonary vessels. 
This is called hypostatic congestion; not infrequently it leads to hypo- 
static pneumonia when irritants are inspired or descend through the 
bronchi to the parts of the lung affected. Postmortem there is often 
a similar hypostatic congestion, but without any evidences of catarrhal 
inflammation of the bronchi, such as always occurs in the cases de- 
veloped during life. 

The lung in passive hyperemia is deep brown in color and heavy. In 
the more acute cases it is moist on section, being infiltrated with serous 
exudate and blood; in chronic cases, as in slow heart-failure, the tissue 
is dry and indurated. Microscopically, the blood-vessels in the alveolar 
walls are seen to be greatly distended, irregular, tortuous, and project 
into the alveoli. Red and white blood-corpuscles are seen within 
the alveoli and in the interstitial tissues. In the later stages the red 
corpuscles either re-enter the circulation or break down to form dark 
pigment-granules within the alveolar epithelial cells, the leukocytes, or 
lying free in the tissues of the alveolar walls. In such cases there are 
at the same time considerable hyperplasia and induration of the con- 
nective tissue of the lung; and the whole process is called cyanotic 
induration. In cases of heart disease with congestion of the lungs there 
are very commonly found in the sputa pigmented epithelial cells and 
leukocytes, such as those described above (Plate 1, Fig. 2). These have 
been called heart-failure cells (Herzfehlerzellen). They are of some 
diagnostic importance. 

Edema occurs most frequently as a result of passive hyperemia 
and is due to disproportion in the expulsive force of the two ventricles, 
the right heart continuing to pump blood into the organ, the left side 
being unable to receive and drive all that is returned. The acute edema 
of nephritis may possibly be due to the inability of the left heart to 
empty because of the continued circulatory hypertension. In other 
cases the edema is the consequence of general septic conditions which 
lead to unusual permeability of the blood-vessels. In this group of 
cases belong the instances of "acute idiopathic edema" which are 
apparently independent of cardiac weakness and probably dependent 
on some form of infection. This is sometimes seen as an acute fatal 
attack in persons suffering from vascular disease, especially of the 
aorta, and in nephritics. Similar edema, not dependent on passive 
congestion, occurs in the parts of the lung surrounding inflammatory 
areas, and in some cases sudden pulmonary edema seems dependent on 
vasomotor relaxation. In cases of stenosis of the larynx, edema of the 
lung may result, from the reduced pressure of air in the alveoli and the 
consequent suction of blood to the pulmonary circulation. In the cases 
of edema due to passive congestion the lungs are dark-red in color, 
firmer than normal, pit on pressure, do not show normal crepitation, 
and on section more or less serous fluid, rendered frothy by admixture 
of air, exudes from the cut surface. In long-standing cases the exuding 
fluid may be dark by admixture of degenerated blood. In the other 
forms of edema the lung may be quite light in color, generally grayish, 
but on section the same frothy serum exudes from the surface. 



DISEASES OF THE RESPIRATORY SYSTEM 



565 



Microscopically, little is to be seen. There is some congestion of the 
septa, with a few epithelial cells and a hyaline coagulum in the alveoli. 

Hemorrhage. — Small punctate hemorrhages occur in cases of severe 
congestion or inflammation, in the hemorrhagic or infectious diseases, 
and in consequence of high blood-pressure, as in death from asphyxia or 
in whooping-cough. .The cause of such hemorrhages is inflammatory or 
degenerative weakening of the vessel walls or an obstruction of the lumen. 
When the former exists, and the latter supervenes, the production of hem- 
orrhage is easier and more extensive. When hemorrhage from congestion 
is combined with serous effusion the lung assumes an appearance not 
unlike that of a hyperemic spleen (splenization) . A form of apparent hem- 
orrhage is seen in cases in which the blood is aspirated from the bronchi. 
In such cases lobular spots of hemorrhagic infiltration are found at the 
bases. Hemorrhagic areas occur also in cases of cardiac decompensation, 
especially from mitral disease. Large hemorrhages into the substance 
of the lungs may be traumatic, or they may be due to rupture of an 
adjacent aneurysm into the lung. Small or large pulmonary hemorrhages 
are at times due to lesions of the nervous system, especially of the base of 
the brain. 

Hemorrhage from the lungs, discharging externally through the 
bronchial tubes, is most commonly due to tuberculosis, and is particu- 
larly frequent in the late stages, when cavities have formed. The im- 
mediate source of the bleeding is generally an eroded vessel in the wall 
of the cavity, and a small miliary aneurysm is commonly found at the 
point of erosion. It may, however, be one of the first signs of the disease 
since very early tuberculous lesions may bleed. Massive hemorrhages 
are at times due to infarction or the rupture of an aneurysm. Occasion- 
ally, hemoptysis is due to congestion of the lungs from cardiac decom- 
pensation, to erosion of small blood-vessels from gangrene, abscess or 
the like, or to vicarious menstruation. 

Hemorrhagic infarcts may occur in the lungs, as in other places, 
from obstruction of the arteries by emboli. The latter come from the 
right heart or from the general venous system, and lodge in the smaller 
branches of the pulmonary artery, frequently at their points of sub- 
division. Very often, however, emboli are not found, or, if so, are so 
small as to have been unable to cause obstruction without the associated 
thrombosis, or there may be purely thrombotic occlusion. Valvular 
lesions and muscular weakness of the heart aid greatly in the produc- 
tion of infarctions by causing a sluggish circulation in the pulmonary 
vessels, and thus encouraging thrombosis. Infarctions are occasionally 
due to thrombosis of the pulmonary veins without obstruction of the 
arteries; more rarely they are caused by occlusion of one of the bronchial 
tubes. The latter condition leads to collapse (atelectasis) of the part of 
the lung associated with that tube, to consequent congestion (see Ate- 
lectasis), and, sometimes, when the congestion is severe, to hemorrhage. 
In addition, it is to be remembered that hemorrhages into the lungs 
are likely to have the shape and appearances of ordinary infarcts, be- 
cause they occupy the area supplied by the bronchus into which the blood 
finds its way. Contributory causes are to be found in emphysematous 
lungs or those with senile or chronically altered arteries. These act as 



566 



A TEXT-BOOK OF PATHOLOGY 



conditions favoring embolism and, secondarily, thrombosis by reason of 
degenerated -vessel walls, and a loss of accommodative power by the 
pulmonary vascular and tissue tension. Infarctions are most frequently 
found in the lower lobes and in the right lung; they are usually multiple 




Fig. 251. — Double hemorrhagic infarct of lung (from a specimen in the collection of 

Dr. Allen J. Smith). 

(Fig. 251) and have the characteristic wedge shape, the base of the 
wedge directed toward the pleural surface. They are hard, airless, dark 
colored, and project above the other parts on section and on the pleural 
surface. The pleural surface is at first shining and dry; later it becomes 
moist, then cloudy, and a layer of lymph appears, sometimes to be fol- 




Fig. 252. — Hemorrhagic infarction of the lung (from a photograph by Dr. Wm. M. Gray). 

lowed by a distinct fibrinous or adhesive pleuritis. Microscopically, 
there is seen a uniform hemorrhagic infiltration of the tissues (Fig. 252) 
and not infrequently hyaline thrombosis of the smaller blood-vessels. 
Toward the apex of the infarct there is more fibrin in the blood-vessels, 
and the main vessel may be found obstructed by an embolus or throm- 



DISEASES OF THE RESPIRATORY SYSTEM 



567 



bus. Small infarcts may be wholly removed through the vascular and 
lymphatic channels after liquefaction and granular degeneration of the 
blood-clot. More commonly a pigmented scar is left. Softening and 
cyst formation may occur, or in cases in which the original embolus 
was infected by micro-organisms, or in which the infarct becomes in- 
fected through the bronchial tubes, abscess or gangrene may result. 

Embolism without infarction is not infrequent in the lungs. An 
interesting form is fat-embolism, resulting from fracture of a bone 
with disorganization of the marrow, and less frequently from traumatic 
disturbances of other fat tissues. When large branches of the pulmonary 
artery are occluded in this way, or when numerous vessels are ob- 
structed, sudden death may result. In other cases there are merely 
great dyspnea and oppression. Air-embolism, embolism of hydatid 
cysts and of portions of tumors are rare. Attention has been called to 
the embolism of placental cells in certain cases of eclampsia. 

HYPERTROPHY AND ATROPHY 

Hypertrophy. — True hypertrophy, in the sense of increase of all the 
constituents of the lung tissue, is extremely rare, and probably only 
occurs when areas of the pulmonary tissue have been rendered useless 
early in infancy or in fetal life. Cases have been observed, however, 
in which a single lung occupied the entire side of the thorax to which it 
belonged, and also a part of the other side, where complete atrophy of 
the other lung had existed. It may be that limited areas of hyper- 
trophy occur more frequently than we at present believe, but evidence 
is wanting. 

Partial Hypertrophy. — The muscular tissue of the intervesicular 
septa and of the smaller bronchioles not infrequently undergoes pro- 
liferation or hyperplasia when there has been obstruction in the air- 
passages, so that greater expiratory force was required. Similarly, the 
elastic tissues may become increased; but these are not instances of true 
hypertrophy. 

Atrophy. — Aside from that which occurs as a part of emphysema, 
atrophy does not take place. 

EMPHYSEMA 

By this term is indicated an increase of the air contained within 
the lungs, either in the normal tubes and alveoli or in the interstitial 
connective tissue. Two varieties of emphysema may be distinguished 
by their essentially different nature. These are the interstitial and the 
vesicular. 

Interstitial emphysema of the lungs is similar to the emphysema 
of the subcutaneous tissues — i. e., the term refers to the existence of air 
within the fibrous tissue of the lung. This occurs in the course of affec- 
tions in which there is some obstruction to the expiration, combined 
with severe coughing or forcible expiratory efforts, leading to rupture of 
the intervesicular septa and extravasation of air. Degenerative or in- 
flammatory weakness of any part of the pulmonary structure would, of 
course, act as a primary cause. Interstitial emphysema is most com- 
monly observed in such diseases as whooping-cough and membranous 



568 



A TEXT-BOOK OF PATHOLOGY 



croup; it may also result simply from straining efforts, as in women 
during labor, or from forcibly blowing wind-instruments, etc. The air 
from the ruptured air-vesicle finds its way into the interalveolar and in- 
tervesicular septa, and, passing along these, eventually reaches the inter- 
lobular and subpleural connective tissue, where it is seen in the form of 
small blebs, movable from place to place. The process may extend to 
the roots of the lungs, and even to the mediastinal tissues or to the sub- 
cutaneous tissues of the neck. When an air-vesicle near the pleural 
surface ruptures, pneumothorax may result. 

Vesicular emphysema is the term used to designate overdistention 
of the alveoli and air-sacs of the lung. Two factors play a part in the 
causation of this condition : first, increase of the pressure under which the 
air exists in the lung; and, second, degenerative or inflammatory weak- 
ness, with loss of elasticity of the lung structure itself. There are 
several varieties, and the causes vary somewhat in each. 

(a) Acute vesicular emphysema results simply from excessive air- 
pressure within the alveoli, and may be more or less widespread. It 
occurs in cases in which inflammatory swelling or mucous secretions 
within the bronchi obstruct the expiration of air, but are not sufficient 
to impede the more vigorous inspiratory force. There results over- 
distention of the alveoli and air-vesicles. Somewhat similar conditions 
are present when the entrance of air into certain parts is impeded by 
obstruction or disease of the bronchi or by consolidations of the pul- 
monary tissue. Localized emphysema of other parts results; the 
term vicarious emphysema is applied to such cases. This is not 
unusual in the lobules of the lung surrounding areas of pneumonic or 
tuberculous consolidation, and may affect an entire lobe or lung when 
the entrance of air into the other lobes or the other lung is prevented 
{compensatory emphysema) . 

Pathological Anatomy. — In these cases of acute and vicarious 
emphysema there is simply overdistention of the alveoli, and the tissue 
presents a paler color than normal and a cotton-like sensation when 
grasped in the fingers. Microscopically, nothing beyond overstretching 
of the septa and some anemia of the vessels is apparent. If the causes 
continue to operate, changes similar to those found in chronic vesicular 
emphysema ensue. 

(6) Chronic vesicular emphysema is the ordinary form of emphy- 
sema, and is sometimes spoken of as substantial emphysema. 

Etiology. — Chronic vesicular emphysema commonly occurs in el- 
derly persons, and is predisposed to by attacks of bronchopneumonia 
and by the existence of other inflammatory and congestive conditions 
of the lungs. The condition not infrequently arises in prolonged 
essential asthma in which. both the chronic bronchitis and the severe 
paroxysmal cough play important etiological roles. All of these con- 
ditions lead to weakness or loss of elastic tissue in the lungs. Heredity 
plays a part in the same direction, and it is supposed by some that there 
is an abnormal lack of development of the elastic tissue in the lungs of 
such persons, rendering them more susceptible to this disease. The 
direct exciting cause of emphysema is increase of the air-pressure within the 
alveoli, and much speculation has been indulged in to discover whether 



DISEASES OF THE RESPIRATORY SYSTEM 



569 



inspiration or expiration plays the more important part in increasing the 
pressure. It seems likely that the expiratory force is the more important 
one, as in the case of constant coughing in chronic bronchitis, the blow- 
ing of wind-instruments, and the constant straining in certain pelvic 
disorders, all of which may lead to emphysema. Unusual rigidity of 
the chest walls, as in abnormal ossification of the costal cartilages, is 
held responsible for some cases, the extra force necessary to expand the 
vesicles being answerable for their dilatation. 

Pathological Anatomy. — The lung increases in size, and very often 
remains distended when the thorax is opened postmortem. The edges 
are rounded; the organ is light in color, and has a cotton-like feeling 
when squeezed between the ringers. On section into it the alveoli may 
be seen to be distended, and there may be cavities of quite considerable 
size, often as large as a pea, and sometimes even that of a cherry or 
plum (Fig. 253). Large spaces of this kind are not unusual near the 



pleural surface; the term bullous emphysema has been used in reference 
to such cases. The pigment matter of the lung is very much lessened, 
and may be distributed in radiating or parallel lines. This lessening 
of the pigment is not alone due to its distribution over a greater space, 
but there is also actual disappearance by removal through the lymphatic 
channels and through expectoration. 

Chronic emphysema may be a general process affecting all parts 
of both lungs, or it may be localized. In the latter case it is the apex 
and anterior edges that are most commonly involved, but spots of 
emphysema may be seen here and there in other parts of the lung, inter- 
spersed with normal tissue. The involvement of the apex and anterior 
portions is due to the fact that the expiratory force is more apt to distend 
these portions of the lung than the lateral and basal portions, which 
receive the uniform support of the sides of the chest and the diaphragm 
as these contract against the lung. 

Microscopically, emphysema is found to consist in enlargement of 
the vesicles and alveoli by distention and by atrophy and disappear- 




Fig. 253. — Emphysema of the lungs (Karg and Schmorl). 



570 



A TEXT-BOOK OF PATHOLOGY 



ance of the intervesicular and inter alveolar septa (atrophic emphysema) . 
Studied from the earliest stage, there will be found, first, overdistention 
of the air-sacs, then a gradual thinning, and finally vacuolization of the 
intervesicular septa at their thinnest parts. Coincidentally, the small 
capillaries are compressed, and are finally converted into hyaline cords. 
The anemia consequent upon this determines additional atrophy and 
degeneration of the septa and fatty degeneration of the loosened epi- 
thelium, so that eventually the whole of the septum disappears. Later, 
adjacent alveoli intercommunicate and large spaces are thus formed. 

The obstruction to the pulmonary circulation due to the obliteration 
of the capillaries leads to collateral hyperemia of the larger branches 
supplying the bronchi, and thus prolongs the chronic bronchitis, which 
in the first instance may have been the cause of the emphysema. Sub- 
sequently, collateral anastomosis between the pulmonary arteries and 
the bronchial system of blood-vessels is established. 

Associated Conditions in Other Organs. — The shape of the thorax 
in emphysema is characteristic. The chest is in a constant state of ex- 
treme inspiration, the clavicles elevated, the sternum protruded, the 
back arched. It has a shape well likened to that of a barrel. The dia- 
phragm is usually depressed and the liver is below its normal position; 
the heart is almost or completely covered over in front and usually 
pressed somewhat backward from the chest wall. 

Pathological Physiology. — The effect of emphysema upon the circu- 
lation is important. The obstruction of the pulmonary capillaries leads 
to increase of pulmonary pressure, and eventually hypertrophy of the 
right heart; later, dilatation of the right ventricle ensues, and character- 
istic cardiac dropsy with general cyanosis may result. 

(c) Senile emphysema is due to thinning of the intervesicular septa, 
the result of the atrophic processes to which old age predisposes. There 
is not necessarily any element of increased air-pressure in the causation 
of this form of emphysema, and the volume of the lung may not be 
notably increased, though the tissue is lighter and the air-spaces are 
found to be increased. The lung is light in color and often collapses 
readily. 

ATELECTASIS 

The term "atelectasis" is applied to two distinct conditions, one 
occurring as a congenital affection, in which the lung has never been 
properly expanded by air; the other occurring in after life, in which the 
lung is compressed or collapsed, so that the alveoli and air-vesicles are 
rendered airless. 

Congenital atelectasis is found in newborn babes in whom the 
inspiratory power has been so deficient, as the result of general weakness 
or compression of the thorax, or of compression of the brain by cerebral 
hemorrhage, that the lungs, or parts of them, have never been expanded. 
It may also take place in a purely mechanical way by obstruction to the 
air-passages by meconium or other foreign matter. 

.Pathological Anatomy. — Congenital atelectasis commonly affects 
the bases and posterior portions of the lung. The area of disease is of a 
dark reddish color; it is rather tough, and on section presents a smooth 



DISEASES OF THE RESPIRATORY SYSTEM 



571 



appearance; pressure gives no sign of crepitation. If a portion be thrown 
into water, it sinks. Usually a considerable part of the lung is involved, 
but sometimes merely lobular areas are affected. By inserting a blow- 
pipe into the bronchi the lung may be inflated, and resumes its normal 
appearance, provided the condition has not persisted for any length of 
time. If the child does not perish, secondary changes take place. The 
epithelium of the alveoli degenerates, more or less proliferation of the 
connective tissues of the septa occurs, and the pleura over the diseased 
area is prone to become thickened. The atelectatic portion of the lung 
in such cases remains collapsed; it is smooth on section, free of pigment, 
and can no longer be inflated. Secondary dilatation of the bronchioles 
and bronchi may ensue. 

It is of interest, in a medicolegal sense, to recognize that atelectasis re- 
sembling the congenital form may be met with in the bodies of infants that 
have lived, breathed, and even cried lustily. 
The explanation of this is that collapse 
occurs some time after birth, and, that as 
the lung has practically still its fetal char- 
acteristics, the resulting atelectasis is the 
exact counterpart of the congenital form. 

Atelectasis in later life occurs under 
a variety of conditions. It may simply 
be the result of compression of the lung by 
pleural effusions, by deformities of the 
chest, by tumors, aneurysms, and the like. 
It may also be met with in cases in which 
the bronchial tubes have become obstructed. 
The larger bronchi may be occluded by the 
pressure of tumors or aneurysms, or by 
foreign bodies, and the resulting atelectasis 
is of considerable extent; the smaller bronchi 
and bronchioles are frequently obstructed 
by intense catarrhal thickening of their 
mucosa, and in consequence lobular areas 
of atelectasis are developed. The latter is 

especially frequent as one of the pathological features of broncho- 
pneumonia (q. v.). 

The explanation of atelectasis as the result of bronchial obstruction 
has occasioned much discussion, and several theories have been pro- 
posed. In some cases it is not unlikely that mucous secretions within 
the bronchi may prevent inspiratory entrance of air into the lungs with- 
out opposing any obstacle to expiration, so that collapse is gradually de- 
veloped. In other cases it is likely that both inspiration and expiration 
are prevented, while the air contained within the air-vesicles is gradu- 
ally absorbed. It is claimed that first the oxygen, later the carbonic 
acid, and finally the nitrogen are absorbed; the collapse of the alveoli 
then becomes complete. It is possible, also, that atelectasis may be 
developed as the result of the failure of respiratory motions on one side, 
or affecting a certain part of the lung. As a result of this, the elasticity 
of the pulmonary tissue would gradually press the air out of the affected 




Fig. 254. — Atelectasis due to 
bronchial obstruction: acute em- 
physema of the unaffected portions 
of the lung (Orth). 



572 



A TEXT-BOOK OF PATHOLOGY 



area, while new air was not supplied by inspiration. Such a condition, 
however, must be rare. 

Pathological Anatomy. — The part affected by atelectasis is dark in 
color and is much reduced in size, so that when lobular areas are affected 
the pleural surface may be considerably depressed (see Fig. 254) . On sec- 
tion, the surface is smooth and generally dry, though in some instances 
passive hyperemia, which is generally present to some extent, reaches 
such a grade that bloody liquid flows freely from the surface of section. 
The term splenization is properly applied to such cases, whereas the in- 
stances in which the surface is dry are often spoken of as carnification. 
The lung does not crepitate, and sinks when placed in water. In the 
earlier stages the diseased portion may be inflated through the bronchial 
tubes; but when the condition has persisted, connective tissue over- 
growth springing from the septa causes permanent induration and 
collapse. The lung in such cases is hard and of a dark color, due to 
the deposit of hematogenous pigment, the result of disintegration of the 
blood present. The bronchi may be compressed, but sometimes atelec- 
tatic bronchiectasis results from the increased pressure of air sustained 
by the bronchi in consequence of the collapsed state of the lung tissue. 

INFLAMMATION, OR PNEUMONIA 

Classification. — Inflammation of the lungs, pneumonia, or pneu- 
monitis may arise in a variety of ways, and present itself in a number 
of widely varying forms, both as to the distribution and the nature of 
the pathological changes in the pulmonary structure. In all cases some 
irritant is conveyed to the lung either (a) from the upper air-passages 
or external world through the bronchi (bronchogenic pneumonia); (6) 
from some other part of the body through the blood (hematogenic 
pneumonia); or (c) from the pleura by direct extension or through the 
lymph-channels (pleurogenic pneumonia). 

Anatomically, pneumonia is classified according to the nature of the 
inflammatory products, and there are thus distinguished: fibrinous 
pneumonia, in which the air-vesicles and terminal bronchioles contain 
an exudate especially rich in fibrin; catarrhal, or bronchopneumonia, 
in which the exudate is composed of an albuminous liquid containing 
numerous epithelial cells and blood-corpuscles; purulent pneumonia, 
in which pus-cells are the noteworthy element in the exudate; cheesy 
pneumonia, in which cellular desquamation and cheesy necrosis are 
prominent ; and productive or fibrous pneumonia, in which there is over- 
growth of fibrous connective tissue. It is to be remembered, how- 
ever, that mixed cases are of frequent occurrence and that the essen- 
tials of inflammation are present in all types. Thus, in many instances 
localized areas of decided fibrinous pneumonia are found in the midst 
of larger areas of catarrhal pneumonia; some distinctly purulent exuda- 
tion may be met with in many instances of fibrinous or catarrhal pneu- - 
monia; and more or less productive inflammation and fibrous overgrowth 
may be seen in any of the other varieties. While typically pure cases do 
occur and homogeneous areas are seen in certain parts of pneumonitic 
lungs, it is not uncommon for different stages of the process to occur side 
by side. Thus in lobar pneumonia the stages of hepatization may vary 



DISEASES OF THE RESPIRATORY SYSTEM 



573 



in nearby sections, and purulent areas may be surrounded by catarrhal 
or strictly fibrinous zones. 

The terms "parenchymatous" and "interstitial pneumonia" are 
sometimes employed, but are of doubtful significance. The proper 
parenchyma of the lungs, the alveolar septa and their contained blood- 
vessels, are never the sole seat of inflammation, and the term "parenchy- 
matous pneumonia," as usually applied to inflammations of the lining 
epithelium of the air-vesicles, is, therefore, misused. It is appropriate 
to call the fibrous variety "interstitial pneumonia." 

Fibrinous Pneumonia 

Definition. — Fibrinous, or croupous, or lobar pneumonia is an acute 
infectious form of pneumonia, generally caused by the Diplococcus 
pneumonias, and usually involving an entire lobe or more than one lobe 
of one or both lungs. Pathologically, it is characterized by an exuda- 
tion within the air-vesicles and terminal bronchioles, mainly composed 
of fibrin; clinically the disease is marked by a definite and character- 
istic course. 

Etiology. — The important factor in the causation of fibrinous 
pneumonia is the Diplococcus pneumoniae (Frankel-Weichselbaum) . 
This micro-organism is found in the sputa and in the lungs, and is un- 
doubtedly the cause of the pneumonia in the great majority of cases, 
but some other micro-organisms seem able to occasion typical fibrinous 
pneumonia. Among these are the pneumobacillus of Friedlander, 
streptococci, staphylococci, the bacillus of typhoid fever, the bacillus of 
influenza, and the Bacillus coli communis. In some cases in which 
bacteria other than the diplococcus are supposed to be the cause there 
is, doubtless, mixed infection; but it must be accepted at the present time 
that a number of micro-organisms are capable of causing the disease. 
The fibrinous pneumonia which occurs in the course of tuberculosis is 
certainly due to secondary infection, and the same thing frequently 
happens in the course of typhoid fever and influenza, though the specific 
bacilli of these diseases may alone cause pneumonia. 

The micro-organisms usually gain access to the lungs through the 
bronchi. In the case of the Diplococcus pneumoniae the frequent oc- 
currence of this organism in the mouth and upper respiratory passages 
furnishes a ready explanation of one source of infection. More rarely 
the bacteria may be directly inspired from without, or, exceptionally, 
they may reach the lungs through the circulation. 

There are certain predisposing factors which have long been recog- 
nized clinically as causes of pneumonia. These probably act by render- 
ing the pulmonary tissues less resisting, or by increasing the virulence 
of the diplococci of the mouth. Among these causes are exposure to cold, 
injury of the lungs by traumatism, fatigue, and systemic depression. 

(For the description of the Diplococcus, see p. 294.) 

Latest studies have placed this disease, at least when caused by the 
pneumococcus, among the acute specific infections. There is almost 
always a bacteremia. While admitting the effect of disposing causes in 
the production of the disease, attention has been called to acute localized 
congestions in the lung or bronchioles, as starting-points of the general 



574 



A TEXT-BOOK OF PATHOLOGY 



involvement. Such, says Cole, are the most likely beginnings of the 
pneumonia because they offer colonizing places for pneumococci. The 
virulence of the bacterium has little relation to its pathogenicity, but 
the more virulent, the more fatal. There is only a slight parallelism 
between the severity of the infection and the extent of the anatomical 
lesions. The leukocytes and their phagocytic power are both increased 
toward the end of an attack. At its height the infection continues by 
reason of a state of balance between the phagocytic- power of the leuko- 
cytes and certain antibodies in the blood on the one hand, and the 
infectious organisms on the other. When the defensive group neutral- 
izes the offensive, the balance is destroyed and crisis takes place. (See 
Immunity and Pneumococcus, pages 269 and 281.) 

Pathological Anatomy. — The lesions most frequently involve the 
lower lobe of the right lung; next in order is the lower lobe of the left 
lung; the apices alone are least frequently involved. In all cases there 
is a tendency to the involvement of a whole lobe, and, as a rule, the 
entire area of disease is affected uniformly and simultaneously. There 
are wide variations, however; for, on the one hand, typical fibrinous 
pneumonia may occasionally appear as a more or less lobular disease 
(particularly in influenza), and, on the other hand, the process may 
spread from one part of the lung to another (pneumonia migrans). In 
typical cases not only is the process uniformly distributed, but it passes 
through distinct stages: first, of congestion, then of consolidation, and 
finally, of resolution. 

State of Congestion or Engorgement. — The affected area is dark-red 
in color; it is swollen and heavy, and on pressure crepitates less than a 
healthy lung. The pleura over the diseased part is dull and lusterless. 
On section through the lung, bloody liquid exudes, and when the part is 
compressed with the fingers this liquid shows a few air-bubbles. The 
condition is simply one of intense congestion, with exudation into the 
alveoli and terminal bronchioles of serous liquid and blood-corpuscles 
(see Fig. 249) . Microscopically, the small blood-vessels of the septa are 
seen to be greatly distended and project inward toward the alveoli. 
Within the latter may be found many red corpuscles, a lesser number of 
leukocytes, and some detached epithelial cells. 

Stage of Consolidation, or Hepatization. — The diseased lung is now 
completely solid and liver-like in consistency (hepatization) . It is 
swollen, and marked on the surface by indentations of the ribs. The 
surface of section is at first red in color (red hepatization, Plate 11), 
but later becomes white or gray, or in elderly persons (in whom the lungs 
are usually darkly pigmented from inhalation of dust) of a variegated 
appearance, resembling granite (gray hepatization, Plate 12). The cut 
surface is entirely dry, and is finely granular on account of the projection 
of small plugs of fibrin from the alveoli and bronchioles. The pleura 
is generally covered with fibrinous exudation. Microscopically, the 
alveoli are found distended with a network or particles of fibrin, in 
which the same cellular constituents as occur in the stage of congestion 
are embedded. The fibrinous network is beautifully demonstrated 
by staining the sections after the method of Weigert (Fig. 255). While 
at first this coagulum is rather uniformly distributed among the cells of 



PLATE ii 




Croupous pneumonia, stage of red hepatization (Bollinger). 



PLATE 12 




Croupous pneumonia, stage of gray hepatization (Bollinger). 



DISEASES OF THE RESPIRATORY SYSTEM 



575 



the exudate, it seems gradually to contract and may, just before its 
liquefaction, appear as irregular masses or balls. Careful examination 
of a lung section will sometimes reveal a point of insertion of the fibrin 
upon the alveolar wall corresponding to the point of insertion of fibrin in 
the adjoining alveolus. It is thought that it is actually continuous in the 




Fig. 255. — Red hepatization of the lung (from a photograph by Dr. Wm. M. Gray). 

two spaces, passing through stomata between the epithelia. The blood- 
vessels are less prominent than in the first stage, although some may be 
seen occluded by hyaline thrombi. As the disease advances to the 
period of gray hepatization the number of leukocytes within the exudate 
increases and the blood-vessels become still less prominent (Figs. 256 and 




Fig. 256. — Croupous pneumonia: beginning Fig. 257. — Advanced gray hepatiza- 
gray hepatization (Karg and Schmorl) . tion (from a photograph by Dr. Wm. 

M. Gray). 



257). This change of appearance is due to destruction of red blood-cells 
and leukocytes, a solution of fibrin by enzymes from leukocytes, and the 
arrival of new leukocytes, which act as scavengers of the destroyed 
material. Under the microscope the exudate has retracted from the 
septa and liquefactive necrosis appears. 



576 



A TEXT-BOOK OF PATHOLOGY 



Stage of Resolution. — Gradually softening of the exudate occurs and 
the lung becomes more moist, the cut surface being gelatinous or trans- 
lucent. Puriform liquid may be squeezed from the surface of section, 
or may be seen in the bronchioles and bronchi. Crepitation is re-estab- 
lished. Microscopically, fatty degeneration of the cells of the exudate is 
apparent. Softening is further contributed to by simple liquefaction. 
The result of these processes is emulsification of the exudate, which is 
finally carried off by the lymphatics or expectorated. 

Resolution occurs by action of the ferments liberated from the infil- 
trated cells upon their disintegration, and somewhat from the ferments 
of the bacteria. The digestion products of the ferment action are ab- 
sorbed, not the cells and fibrin as such. 

Before the process of resolution is completed the epithelial cells 
of the alveoli and bronchioles proliferate, so as to repair the diseased 
portions. At the same time proliferative changes may be seen in the 
tissues of the septa. These conditions exist throughout the disease to a 
slight extent, but become more apparent in the stage of resolution. 
Eventually the lung is restored to its previous condition. 

Unusual Characters. — In some cases the pathological changes 
vary somewhat from the typical form described. Not rarely there are 
considerable congestion and even edema of the lung throughout the 
disease; in drunkards or cachectic individuals the exudate is more mark- 
edly hemorrhagic than is usually the case; and sometimes, particularly 
in instances accompanied by streptococcus infection, the exudate is 
more cellular than customary. A very distinct mucinous character is 
assumed where the causative organism has been the Streptococcus 
mucosus or the Friedldnder bacillus, with the latter germ fibrin being 
very inconspicuous. 

In thinking of the outcome of a pneumonia one must not forget that, 
in this acute lobar form at least, large parts of the respiratory tissue are 
functionless, and are deprived of blood-, lymph-, and probably nerve- 
supply. The result within the lung will depend upon the power of the 
leukocytes to combat the bacteria and to dissolve the fibrin. If they be 
inadequate in number or in function, delayed resolution may result, a 
condition predisposing to abscess, gangrene and fibroid pneumonia. 
Moreover if, during resolution, putrefactive microbes gain entrance 
gangrene may at once supervene. It appears that any lesion which 
severely damages the bronchial wall and favors bronchiectasis reduces 
the chance of complete restitution. 

Associated Lesions and Pathological Physiology. — The portions 
of the lung not involved by the pneumonic process are usually some- 
what emphysematous and congested, and edema may develop. The 
latter is, however, not so common as has often been assumed. The 
larger bronchial tubes, as a rule, remain normal or, at most, become 
congested. The finer bronchi are more frequently hyperemic, and 
excess of mucus coats the surface. In practically every case there is a 
certain degree of fibrinous pleurisy, either on the costal surface of the 
pleura or between the lobes, and at times one finds a serous fluid separat- 
ing the layers of this sac; generalized pleuritis is however uncommon. 
The pleurisy is directly attributable to the micro-organism which has 



DISEASES OF THE KESPIRATORY SYSTEM 



577 



caused the underlying pneumonia and arises as a migration of the germs 
from the alveoli or along the septa of the organ. 

Though fibrinous pneumonia is sometimes a local infection anatomic- 
ally, systemic intoxication is usually present, and general infection may 
further aid to develop widespread pathological changes. Leukocytosis is 
present in the great majority of cases; its absence is generally significant 
of unusually intense systemic intoxication. In fatal cases white clots 
are often detected in the chambers of the heart and in the large blood- 
vessels leaving the heart. Cardiac and respiratory embarrassment, 
often ascribed to mechanical causes, such as heart-clot or extensive 
consolidation, is probably in many cases due to the action upon the 
nervous system of the toxins of the disease. Myocardial degenerations 
aid in producing circulatory weakness. The heart muscle and the 
kidneys may suffer parenchymatous degeneration as in other febrile 
infections, and acute exudative inflammation (myocarditis, nephritis) 
may occur in either of these organs. Albuminuria is not infrequent, and 
albumoses may be found in the urine, especially during the stage of 
resolution. Calcium, chlorin, and sodium are decreased in excretion, 
while magnesium and potassium are increased. The splenic enlarge- 
ment is of the acute septicemic variety. 

Pericarditis is frequent, and endocarditis, either of the simple or of 
the malignant type, is more common than in any other acute infection, 
excepting rheumatism. Meningitis is occasionally noted. 

Fibrinous or pseudomembranous bronchitis, laryngitis, gastritis, 
colitis, and cystitis are sometimes met with. Inflammation of the joints 
and abscesses in various organs may occur. 




Fig. 258. — Induration of the lung (carnification) in a case of pneumonia of five weeks' 
duration: a, a, a, New connective tissue of the septa; 6, intra-alveolar proliferation of con- 
nective tissue; c, c, c, desquamated epithelium in the alveoli; e, e, e, new blood-vessels; 
/, lining epithelium of the alveoli (Kaufmann). 

Unusual Terminations. — Secondary infection with pyogenic micro- 
organisms may lead to termination in abscess ; or this result may be due 
to the fact that the pneumonia was primarily caused by active pus 
formers. The affected area may suffer gangrene even more commonly 
than suppuration. Gangrene is especially prone to occur when the 
exudation is distinctly hemorrhagic and in cases in which the circu- 
lation is specially weak. Finally, resolution may be delayed and pro- 
ductive changes may occur in the septa and even within the alveoli. 
There results a solidification (carnification) of the lungs, or, as it is 
termed, fibrous pneumonia (Fig. 258). 

37 



578 



A TEXT-BOOK OF PATHOLOGY 



Bronchopneumonia 

Definition. — Bronchopneumonia, or lobular pneumonia, sometimes 
also called catarrhal, is an acute inflammatory affection of the pulmonary 
tissue, occurring in localized areas and consequent upon inflammation of 
the terminal bronchioles and their adjacent alveoli. Pathologically, the 
disease is characterized by inflammation of the terminal bronchioles and 
by exudation into the alveoli of albuminous liquid containing desqua- 
mated epithelial cells, together with red blood-corpuscles and leukocytes 
in varying number; clinically, the disease is marked by an indefinite and 
irregular course. 

Etiology. — Lobular pneumonia may be produced experimentally 
in animals by causing them to inhale steam or various irritating vapors. 
Still more characteristic lesions are produced when the vapors inhaled 
hold decomposing organic matter in suspension. The same result 
is accomplished by cutting the vagus nerves, as a consequence of which 
the vocal bands and esophagus are paralyzed and irritating secretions 
and particles of food are conveyed into the lung by inspiration. A 
similar thing may occur by the abolition of the pharyngeal reflex under 
the influence of ether. In man, tumors, enlargements of the thyroid 
gland, or inflammatory exudation may compress the vagi and lead to 
forms of pneumonia similar to the experimental pneumonia of dogs. 
Somewhat analogously, in the late stages of various diseases, particles of 
food and mucous secretions may sink to the dependent parts of the lungs, 
or may be drawn in by the inspiratory air and set up lobular pneumonia 
in the parts already predisposed to inflammation by hypostatic congestion 
(hypostatic pneumonia). Of the same etiological sort are the catarrhal 
pneumonias which occur in diphtheria, epithelioma of the larynx, and 
inflammatory conditions of the mouth and pharynx, in which irritating 
particles are carried to the finer bronchi by inspiration (aspiration pneu- 
monia, deglutition pneumonia). Catarrhal pneumonia of this kind is not 
infrequent in the newborn as a result of vigorous inspiratory efforts made 
while the head is descending through the vagina. 

Most frequent, however, of all forms of bronchopneumonia is that 
which occurs in the course of measles, whooping-cough, influenza, or 
other infectious fevers attended with bronchitis. The manner of in- 
volvement of the alveolar structures will presently be described; for the 
present it may be said that the inflammatory process extends from the 
bronchi by continuity and contiguity, or by aspiration of irritating 
bronchial secretions. It would seem also that insular pneumonia of the 
kind under discussion could arise where the bacteria are carried to the 
lungs via the blood stream, especially in lungs already the seat of edema 
or hypostatic congestion. 

The immediate cause of bronchopneumonia is some bacterium, 
the most frequent being the Diplococcus pneumoniae, which occurs in 
over 50 per cent, of all cases, either alone or in combination with the 
Streptococcus pyogenes, staphylococci, the pneumobacillus of Friedlander, 
the bacillus of influenza or of typhoid fever, or the Bacillus coli communis. 
Any of the other forms named, and especially the pyogenic micrococci, 
may cause bronchopneumonia without the diplococcus of Frankel; but in 
the case of fevers (typhoid fever, influenza) in which the specific micro- 



DISEASES OF THE RESPIRATORY SYSTEM 



579 



organisms are found there is usually mixed infection with the Diplococcus 
pneumonice. 

Pathological Anatomy. — The lesions vary somewhat in different 
cases, and we may distinguish three important types: the simple, or 
ordinary catarrhal bronchopneumonia, the hypostatic form, and aspira- 
tion pneumonia. 

X. Simple Bronchopneumonia. — The lung in such' cases presents 
more or less distinct external appearances. On the pleural surface may be 
seen lobular areas of dark- or light-red or grayish color, which are some- 
what elevated and harder than the normal lung. Surrounding these the 
pulmonary tissue is emphysematous, while here and there may be seen 
dark-red or lead-colored and somewhat depressed areas of pulmonary 
collapse (atelectasis). The lung as a whole is crepitant, while the pneu- 
monic and atelectatic areas are consolidated and airless and sink in water. 



On section through the lungs the same general appearances are visible, 
though the consolidated patches are most abundant near the surface. 
Both lungs are, as a rule, involved, and any portion is liable to the dis- 
ease. The smaller and medium-sized bronchi and the bronchioles contain 
mucopurulent secretion, which may be squeezed out ; the areas of pneu- 
monic consolidation are smooth and moist on the surface of section, or 
exceptionally somewhat granular as a result of admixture of some fibrin- 
ous exudate. Occasionally there may be puriform liquid or small purulent 
collections around the bronchiole in the center of the lobule. The area of 
collapse (atelectasis) is dark red, as a rule, and on pressure bloody liquid 
exudes. 

In the very earliest stages of the disease the areas of consolidation 
and collapse may be inflated by inserting a tube into the bronchus 
supplying the part and by blowing gently into it. Later this is not pos- 
sible, as the consolidation increases. At the same time it is noted that the 
consolidated areas become lighter in color, until at last they are grayish 
yellow; while the areas of collapse become pneumonic and present a 
similar change of color. 




Fig. 259. — Catarrhal pneumonia (Karg and Schmorl). 



580 



A TEXT-BOOK OF PATHOLOGY 



Microscopically, the terminal bronchioles and alveolar passages 
present somewhat swollen walls and contain variable amounts of fluid 
exudate with many desquamated cells. In the areas of consolidation 
the alveoli and the air-sacs are filled with liquid and variable numbers of 
epithelial cells, red corpuscles, and leukocytes (Fig. 259). The epi- 
thelial cells are desquamated from the lining membrane either singly 
or in groups, and there is evidence that active proliferation is taking 
place as well. In most cases the number of red corpuscles and leuko- 
cytes is small, but in some instances, particularly in cases in which 
streptococci and staphylococci are operative, the exudation may be 
quite hemorrhagic or, later, purulent. The alveolar septa regularly pre- 
sent considerable round-cell infiltration, and the blood-vessels are sur- 
rounded by emigrated leukocytes. The blood-vessels in the septa are 
distended and tortuous. 

The atelectatic areas present even greater congestion of the blood- 
vessels, and the alveolar cavities are obliterated by the collapse of the 
walls, or contain, at most, a little hemorrhagic exudate. The epithelial 
cells tend to lose their characteristic shape and become cuboidal. 

As resolution advances, the cellular exudate becomes lighter in color 
as a result of fatty degeneration, and eventually it is absorbed or ex- 
pectorated. Coincidently the round-cell infiltration disappears from the 
septa, and the pulmonary tissue returns to the normal, excepting that 
the epithelial cells of the alveoli tend to remain more or less cuboidal 
for a time. Resolution probably takes place as in the case of fibrinous 
pneumonia. 

The form of bronchopneumonia due to the hemolytic streptococcus has 
gained in importance because of its severity during the late war and 
because of its frequent association with measles. It is probably broncho- 
genic and follows in many ways the lobular type here discussed but is 
distinguished from it by the fact that it is almost entirely limited to the 
bronchi, their immediately adjoining alveoli and to the fibrous septa of the 
lung. The bronchial mucosa is the seat of a purulent inflammation 
showing many streptococci, the lumen being full of pus, while the wall and 
peribronchial tissues, inclusive of nearby septa, show many mononu- 
clears and cocci. Alveoli, however, contain usually catarrhal and fibrin- 
ous exudate with a moderate number of polynuclears. The infection 
tends to spread along the septa to other parts of the lung and to the 
pleura, so that pseudolobar forms appear and suppurative pleuritis 
arises. Sectioning such a lung gives the impression at times of large 
diffuse tubercles surrounded by congestion and edema but search will 
usually reveal in each nodule a bronchus plugged with pus. Abscesses 
within the lung and interlobar empyema frequently result from this 
condition. Resolution occurs in the usual manner but the peribronchial 
fibrosis seems marked. 

Pathogenesis. — The manner of development of the lesions is of con- 
siderable interest. In the ordinary catarrhal bronchopneumonia now 
under discussion there is always a primary bronchitis of the terminal 
bronchioles, a bronchiolitis, or capillary bronchitis, as it is termed. This 
may be spread to the alveolar structure in several ways. In most in- 
stances, no doubt, the inflammation travels downward along the bron- 



DISEASES OF THE RESPIRATORY SYSTEM 



581 



chioles to their termination by continuity, or outward through their 
walls to the surrounding alveoli by contiguity. In either case there 
results a patch of catarrhal pneumonia surrounding a terminal bron- 
chiole. Less commonly the affected lobule first becomes atelectatic and 
then pneumonic. The atelectasis results from the obstruction of the 
bronchioles by mucus or by their swollen walls, and is due to the gradual 
absorption of the air contained within the alveoli and the inability of 
more to enter (see Atelectasis) . Subsequently the collapsed area becomes 
inflamed by the entrance of micro-organisms from the bronchioles or by 
extension of surrounding inflammation. 

Unusual Characters.^— Marked variations are seen in the nature of 
the process and in its distribution. In some instances there is but little 
pneumonic consolidation, while the bronchiolitis, or capillary bronchitis, 
is a striking feature. In other cases the exudate is decidedly hemor- 
rhagic or purulent, and it may in certain areas be quite fibrinous. Re- 
garding the distribution, the most striking variation is the tendency 
in some cases to lobar involvement by confluence of the lobular areas 
(pseudolobar form) . 

Associated Lesions. — The constant association of bronchitis has been 
sufficiently noted. Pleurisy is less common than in fibrinous pneu- 
monia, but the patches near the surface are frequently covered with 
fresh pleural exudation. It has long been recognized that purulent 
pleurisy is more apt to occur after pneumonia in children than in adults, 
and in many of these cases the antecedent pneumonia is catarrhal. Wide- 
spread toxic and infective lesions may occur, as in fibrinous pneumonia. 

Unusual Terminations. — In cases in which micro-organisms, more 
virulent than usual, cause the pneumonia, suppuration and gangrene 
may result. Fetid and pultaceous foci, or purulent collections sur- 
rounded by considerable areas of congestion and inflammatory edema, 
result. In other instances the process of resolution is slow, and fibroid 
overgrowth of the septa and proliferation of connective tissue within the 
alveoli ensue, with the production of more or less extensive sclerotic 
hardening and contraction of the lung structure. Within such areas 
the alveolar exudate may lie for a long time as a fatty mass; but this is 
very unusual; and true caseation, of which so much was formerly said, 
does not occur. The instances in which this was supposed to have 
occurred were cases of subsequent infection with tubercle bacilli, or 
cases of tuberculous pneumonia ab initio. 

2. Hypostatic Pneumonia. — The bases and posterior portions of the 
lungs are commonly involved in these cases. The process occurs as a 
terminal affection in many diseases. It begins as an intense hypostatic 
congestion and hemorrhagic edema of the dependent parts of the lungs. 
Subsequently, the irritants which make their way to the congested area 
through the bronchi set up a form of inflammation of the terminal 
bronchioles and air-vesicles which is largely catarrhal, but more fibrinous 
than ordinary bronchopneumonia. The inflammatory process is also 
more diffuse, and is, at the most, insignificant compared with the ante- 
cedent and associated congestion and edema. 

3. Aspiration Pneumonia. — Of the dust which we constantly inhale, 
the greatest part is arrested in the upper air-passages or in the larger 



582 



A TEXT-BOOK OF PATHOLOGY 



bronchi, and is expectorated. A part, however, reaches the finer bronchi 
and bronchioles, and sets up a certain amount of local irritation and 
congestion, with desquamation of epithelial cells and emigration of 
leukocytes. Ordinarily, these processes are exceedingly trivial and can 
rarely be demonstrated. In persons, however, whose occupations 
(e. g., steel-grinding, coal-mining, marble-cutting, etc.) subject them to 
excessive dust inhalation the pulmonary changes are extensive and 
severe. This is one form of aspiration bronchopneumonia, but the irri- 
tation rarely stops at the point of catarrhal inflammation; on the con- 
trary, the irritant particles penetrate the walls of the bronchioles and 
are distributed by the lymphatics, causing fibroid changes of greater or 
less extent. The pneumonia thus produced is, therefore, more appro- 
priately considered as a form of fibrous pneumonia (q. v.). 

In the course of various affections of the pharynx, larynx, trachea, 
and bronchi during anesthesia, as well as in cases in which through palsy 
of the^ larynx,| or through general depression, particles of food or secre- 
tions of the mouth enter the air-passages, irritating matters may be in- 
spired or " aspirated" into the finer divisions of the bronchial system. 
As we shall see under the subject of gangrene of the lung, the lesion 
usually begins as bronchitis and peribronchitis from which the abscess 
most infrequently arises, since while the primary change is catarrhal, 
leukocytes, blood and fibrin usually appear early. 

When the aspirated object is small and reaches a fine tube, the lesion 
is usually limited and isolated, while a large object occludes a medium 
sized bronchus, causing atelectasis, hyperemia, edema and true pneumon- 
itis, often followed by abscess or gangrene. 

Cheesy or Tuberculous Pneumonia 

Definition. — Cheesy or tuberculous pneumonia is an acute or sub- 
acute form of pneumonia caused by the tubercle bacillus, involving 
lobular areas or, by confluence of such, an entire lobe or lung. Patho- 
logically, it is characterized by proliferation and desquamation of epi- 
thelial cells, infiltration of the alveolar septa, and, finally, by cheesy 
necrosis in the area of disease. Clinically, the disease presents itself 
as a more or less acute pneumonic tuberculosis. Caseous pneumonia is 
frequently associated with miliary or peribronchial tubercles, affecting 
the alveoli adjacent to the tubercles. 

The pneumonic form of phthisis florida is a caseous pneumonia. 
Bronchopneumonia of coccus origin may supervene upon chronic ulcera- 
tive phthisis, or tuberculous lesions may be implanted upon a pneumonia. 

Etiology. — Cheesy pneumonia as an independent condition is 
more common in children than in adults. The immediate cause is the 
tubercle bacillus. Infection occurs by rupture of a tuberculous gland 
or cavity into one of the bronchi and dissemination of the infective 
material throughout the lung. Likewise, bacilli may be inhaled from 
outside, or from tuberculous foci in the bronchi, larynx, or nose. In 
cases of disseminated tuberculosis of the lungs areas of caseous pneu- 
monia are habitually encountered in the pulmonary structure between 
the tubercles. Finally, infection may take place through the blood, 
but the occurrence of caseous pneumonia rather than miliary tubercu- 



PLATE 13 




Subacute caseous (tuberculous) pneumonia (Bollinger). 



DISEASES OF THE RESPIRATORY SYSTEM 



583 



losis in such cases is assuredly rare. Theoretically, it is possible to 
have a sudden and overwhelming generalization of the tubercle bacil- 
lus with involvement of a whole lung, but such an occurrence is rare. 
Such cases have been described, but it is difficult to estimate the impor- 
tance of the tubercle bacillus in the presence of other germs capable of 
producing the inflammation. The process is a catarrhal pneumonitis 
universalis without the tubercular changes characteristic of caseous 
pneumonia. 

It has, indeed, been questioned whether the tubercle bacillus alone 
can cause this caseous pneumonia, since the typical tuberculous in- 
flammation is a productive one of lymphatic or interstitial origin. On 
the other hand, a caseous pneumonitis without tubercle bacilli is not 
known. In those cases reported as primary difuse tuberculous pneu- 
monia the pre-existence of a focus discharging bacilli into the trachea 
or bronchi could not be satisfactorily excluded. 

Mixed infection with Diplococcus pneumoniae is not infrequent, but 
it is not, as. some investigators have maintained, essential to the disease. 

Pathological Anatomy. — In its most typical form caseous pneu- 
monia is a lobular process .beginning around the terminal ends of the 
bronchioles, where the infective material lodges. The lung presents on 
section areas of consolidation not unlike those seen in catarrhal broncho- 
pneumonia. At first these are congested and red in color, but very soon 
degenerative changes cause a grayish or yellowish color. The surface 
of section is usually smooth, but often somewhat granular from asso- 
ciated fibrinous exudation. When abundant infection has occurred the 
areas may be thickly set, and a lobar form is thus established (Plate 13) ; 
or there may be a gradual involvement of new areas, receiving their 
infection from those first formed, causing a similar, but less uniform, 
lobar pneumonia. 

The distribution of caseous bronchopneumonia depends upon its 
origin. If this be from the upper air-passages, the involvement may be 
more or less regular and symmetrical, while if entrance of the bacilli 
be gained through a rupture of a gland into a bronchus, it will follow the 
course of this tube and spread from it. 

Caseous pneumonia shows no tendency to resolution, but, on the 
contrary, tends to progressive cheesy degeneration, and at last to the 
formation of cavities. The entire lung may be riddled with small ex- 
cavations, presenting ragged, cheesy walls. Usually the cavities are 
small, even though there be few; exceptionally, large ones are seen. 
Though resolution does not occur, limited areas may be healed by reactive 
fibrous overgrowth springing from the alveolar septa and encapsulating 
the diseased area, or penetrating it, and transforming the whole into a 
fibrous mass. 

Microscopically, the exudation has many of the characters seen in 
catarrhal bronchopneumonia. Essentially, the exudate is cellular, 
and is principally composed of large epithelial cells. These are the des- 
quamated and proliferated lining cells of the alveoli. A smaller number 
of red blood-corpuscles and leukocytes is noted, but they are unessential. 
Sometimes a fibrinous network may be seen in the alveoli, but quite as 
often this is wholly wanting. The blood-vessels are engorged at first, 



584 



A TEXT-BOOK OF PATHOLOGY 



and the septa are infiltrated with round and spindle cells. The walls 
of the blood-vessels themselves may be thickened by proliferation of 
the connective tissue. As the process advances the cellular exudate 
and the alveolar walls as well undergo cheesy degeneration, and pre- 
sent a granular appearance under the microscope (Fig. 260) . 




Fig. 260. — Peribronchial tubercle of the lung and caseous pneumonia of the adjacent 

alveoli. 

Associated Lesions. — Cases of typical caseous pneumonia, as above 
described, are rare; as a rule, more specific tubercular lesions (tubercles) 
are associated. The smaller bronchi are commonly attacked in asso- 
ciation with caseous pneumonia, and tuberculous bronchitis and peri- 
bronchitis tending to cheesy change result. The pleura may be 
covered with inflammatory exudation, or may present miliary tubercles 
over the area of disease. Associated pleural involvement is especially 
common between the lobes. The lymphatic glands of the anterior 
mediastinum and around the bronchi are frequently enlarged, and 
may be cheesy in the later stages. 

Fibrous Pneumonia 

Definition. — Fibrous, or productive, pneumonia is a chronic process 
resulting from continued irritation, and involving small or large areas 
of the pulmonary structure. Pathologically, it is characterized by over- 
growth of connective tissue, and clinically it is marked by signs of more 
or less extensive mechanical impairment of the pulmonary functions. 

Classification. — Several quite distinct forms, depending upon differ- 
ent modes of causation, may be described. The principal varieties are: 
(1) The pneumonokonioses, or fibrous pneumonias, due to dust inhala- 



DISEASES OF THE RESPIRATORY SYSTEM 



585 



tion; (2) the secondary indurative pneumonias, such as sometimes follow 
croupous, catarrhal, or caseous pneumonia, or more frequently chronic 
congestion of the lungs or atelectasis; (3) pleurogenetic fibrous pneu- 
monia, in which the process arises by extension of chronic pleural dis- 
ease; and (4) peribronchial and perivascular fibrous pneumonia, in which 
the process follows the bronchi and pulmonary arteries. 

1. Pneumonokoniosis. — Of the dust we constantly inhale, but a 
small part reaches the finer divisions of the bronchial tree. Most of it 
adheres to the walls of the upper respiratory tract and is discharged with 
the sputa, either free or enclosed in leukocytes or epithelial cells (dust- 
cells). When fine particles reach the terminal bronchioles and alveoli 
they occasion catarrhal inflammation, marked by proliferation of the 
epithelium and exudation of leukocytes. These cells may envelop 
the irritant particles and remove them through the expectoration. 
When, however, the dust has sharp edges (as in coal-dust, iron-dust, 
marble-dust, etc.), and especially when the quantity inhaled is con- 
siderable, removal by expectoration becomes more difficult. In such 
cases the foreign particles penetrate the walls of the bronchioles and 
alveoli) passing between the epithelial cells. They may be arrested in the 
alveolar septa and in the tissue surrounding the bronchioles by the for- 
mation of a zone of inflammatory exudation, which eventually organizes, 
forming a fibrous capsule. Some of the particles, however, move along 
the lymph-spaces into the lymphatic vessels, being carried by phagocytes 
or floating free in the liquid. These particles may be arrested at various 
points along the lymphatics, and may occasion fibrous thickening of the 
vessels or of the perilymphatic tissue. The greater portion, however, 
passes to the lymphatic glands at the root of the lung and surrounding 
the bronchi, and indurative enlargement of these structures results. In 
exceptional instances the irritant particles may be conveyed still further, 
being deposited in the glands about the smaller curvature of the stomach 
and beneath the fissure of the liver. This unusual distribution in a direc- 
tion opposite the usual lymphatic current is explained by the assumption 
that obstruction of the larger pulmonary lymphatics causes a reversal 
of the current. Metastatic distribution of dust-particles may also be 
due to rupture of one of the affected lymphatic glands into a vein. (See 
discussion of Pneumonokoniosis, page 105.) 

The study of this subject has received in late years considerable 
impetus through the activity in the investigations upon occupational 
diseases. The observations have supported the data given in the 
foregoing paragraph but since they throw more light upon the genesis 
of pneumonokoniosis and its relation to tuberculosis, a brief review of 
the results is profitable. The forms usually encountered are anthracosis 
from coal dust, chalicosis or silicosis from flint or silicious dust, siderosis 
from metal dust; these forms produce more chronic lesions while dust 
in gold mines and from crushed slag give lesions resembling acute pneu- 
monias. Insofar as organic dusts are concerned, it seems to be the gen- 
eral opinion that no fibrous pneumonia results from their inhalation. 
Acute respiratory symptoms arise after breathing vegetable, rag or hair 
dusts but these are probably due to some protein intoxication or to other 
factors involved in the industry concerned jtuberculosis occurring in persons 



586 



A TEXT-BOOK OF PATHOLOGY 



breathing organic dusts is more readily explained as being favored by 
general insanitary conditions than by pulmonary susceptibility increased 
by the dust. 

The inhalation of all dust results in some degree of reactive catarrh 
on the respiratory surface, a process that seems to remove larger par- 
ticles. Mavrogordato intimates that the more the mucous and cellular 
reaction, the more the dusts will be eliminated, only the tiny particles 
that excite little inflammation remaining long enough to be absorbed 
by phagocytes. The effect upon the lungs varies directly with the 
accumulation of particles and the length of time to which the person 
is exposed to the dust. It is a matter of common observation that city 
dwellers coming to autopsy usually show some coal pigmentation under 
the pleura and in the 'glands, while miners who have followed their 
occupation for many years may have absolutely black lungs. The 
amount of fibrosis varies in the the same manner. There are however 
certain cases which, though exposed to identical surroundings, show more 
pigmentation and fibrosis than others. Therefore some predisposing 
circumstances must exist, but their nature is not well understood. 
Perhaps insanitary households and vicious living may act as favoring 
factors. There is no evidence today that pneumonokoniosis per se 
predisposes to tuberculosis but on the other hand it would seem that 
the fibrosis produced actually increases the pulmonary resistance. 

The kinds of dust that are most dangerous are those which are 
spread about in the most finely divided form — flint and silica, while coal 
and iron dusts are less dangerous because the particles are larger. 
When the granules are in the neighborhood of one micron in size they 
are most readily taken up by phagocytes, this size seeming to be too 
small to cause much local reaction. Silica seems to have the power 
to form thin non-irritating plaques over the mucosa from which absorp- 
tion goes on slowly, while coal stays in separate granules. Inorganic 
particles are also dangerous to the degree that they are sharp or jagged. 
Organic dusts are only of importance in fibrosis to the extent that they 
contain inorganic matter. 

Pathological Anatomy. — The appearance of the lung varies with 
the amount of dust inhaled and with its nature. In the early stages, 
such as are found at autopsies upon city dwellers, gray or black areas 
are seen at the lobular divisions under the pleura, about which, if closely 
scrutinized, one will find gray lines running into the surroundings within 
the lung or under the serous membrane. The hilum glands are slighty 
enlarged, firmer than normal and of a dull lead color. In cases of 
moderate degree small areas of fibrous thickening, with puckering, are 
the only abnormality. On section, these are found to be hard and of 
grayish color; often, however, darkly pigmented, owing to the character 
of the particles inhaled as well as on account of the formation of hem- 
orrhagic pigmentation. The fibrous tissue may be arranged in a stellate 
fashion, or concentrically around a nucleus of foreign matter. Secondary 
changes are not uncommon; calcification is frequently observed, and true 
bone-formation is occasionally noted. Such areas of localized pneu- 
monokoniosis are very commonly met with near the apices. 

Where the condition has lasted for years the organ will be irregularly 



DISEASES OF THE RESPIRATORY SYSTEM 



587 



deformed and of a gray or black color, more intense at the bases. Large 
areas of induration may completely destroy the vesicular character of 
the lung structure. Firm bands of connective tissue may follow the 
bronchi and radiate into the peripheral portions of the lung, or thickened 
trabecule may pass from the pleural surface toward the 
interior, or again, a more uniform sclerosis may exist throughout the 
organ. The organ is contracted; the pleura, as a rule, is thickened and 
drawn inward; and the bronchi may be widely dilated as a result of 
the traction of the contracting connective tissue and as a consequence 
of accumulating secretions within. Extensive adhesions to the chest 
wall often cause deformities of the chest, and the pericardium, heart, 
and other mediastinal structures may be drawn from their normal 
positions. Examination by rr-ray will reveal shadows radiating from 
the hilum in an irregular manner, and diffuse mottling, corresponding 
for the first to the peribronchial thickenings, for the second to local 
deposits of pigment surrounded by fibrosis. 

In rare cases the epithelium of the alveoli and finer bronchioles 
proliferates, and later undergoes a certain amount of fatty degenera- 
tion, giving rise to an appearance not 
unlike caseation. In still other cases 
necrosis, suppuration, and cavities (non- 
tuberculous) are observed. 

Microscopically. — In the beginning 
stages round-cell infiltration and con- 
nective-tissue proliferation may be seen 
around the foreign particles in the 
septa, and a certain amount of catarrhal 
inflammation may be present in the 
alveoli. Sharp-edged particles often oc- 
casion small hemorrhages. In the later 
stages dense sclerotic tissue characterizes 
the process. Proliferative inflammation 
of the epithelium of the alveoli may be 
present, but more often the cells undergo 
atrophy and disappear. 

2. Secondary fibrous pneumonia 
sometimes occurs after croupous or 
catarrhal pneumonia, or atelectasis, and secondary to chronic pleurisy 

,t. e f. (Kaufmann). 

in these cases appears m the form of 

uniform or localized induration of the pulmonary structure. It is due 
to reactive inflammation of the septa, causing thickening of the latter, 
as well as proliferation within the alveolar exudate. Similar reactive 
fibrous change is seen in some cases of caseous pneumonia, and in 
chronic phthisis the cavities are quite generally walled by fibrous 
tissue. Finally, chronic congestion of the lung, such as occurs in val- 
vular diseases of the heart, particularly mitral disease, frequently leads 
to diffuse sclerosis of the lung. Such cases are distinguished by dilatation 
of the veins and by hematogenous pigmentation. 

3. Pleurogenic fibrous pneumonia is an occasional consequence 
of chronic pleurisy. The lung presents on section dense trabecule of 




588 



A TEXT-BOOK OF PATHOLOGY 



fibrous tissue, which extend from the thickened and sclerotic pleura 
deep into the pulmonary structure (Fig. 261). 

4. Peribronchial and perivascular fibrous pneumonia may be asso- 
ciated with the pleurogenic form, or the overgrowth of connective tissue 
around the bronchi and vessels may start at the root of the lung and 
extend toward the periphery. The latter form has been described by 
some observers as especially liable to result from syphilis. More moder- 
ate peribronchial and perivascular fibrous pneumonia occurs in asso- 
ciation with other forms, as the pneumonokonioses and secondary 
fibrous pneumonias, but in these cases it is but a minor part of the 
process. 

Congenital Syphilitic Pneumonia. — A form of productive pneumonia, 
as distinguished from fibrous pneumonia in the strict sense that the latter 
is characterized by formation of sclerotic fibrous tissue, is met with in 
congenital syphilis. This may be in the form of pneumonia alba or an 
interstitial overgrowth spreading out from the hilus. 

Purulent Pneumonia 

Definition. — Purulent pneumonia is an acute form of pneumonia 
in which the exudate undergoes purulent softening, usually caused 
by the pus producing cocci. Pathologically, it is characterized by 
purulent and hemorrhagic exudation in the connective tissue, lymphatic 
channels, or terminal bronchioles and alveoli; and clinically it is marked 
by evidences of intense septic infection as well as by great pulmonary 
embarrassment. This subject is given a separate heading by reason 
of its clinical rather than pathological importance, as the dominant 
factor is septicemia. 

The infection in purulent pneumonia may reach the lungs through 
the bronchi (bronchogenic), the blood-vessels (hematogenic), or the sub- 
pleural lymphatics (pleurogenic or lymphogenic) . 

Bronchogenic purulent pneumonia has already been referred to 
in the description of fibrinous pneumonia and catarrhal broncho pneu- 
monia. It is particularly frequent in the latter, in some cases of which 
considerable purulent exudation may be seen in the alveoli or, in the 
form of small purulent collections, in the intervesicular septa. The 
pathological changes are those of catarrhal pneumonia, with an excessive 
infiltrate of polynuclear leukocytes. These are instances of intense 
infection, and the majority of such cases are due to the Streptococcus 
pyogenes or to staphylococci. The pneumococcus may, however, be 
found alone. The most decided purulent bronchopneumonia is seen in 
instances of aspiration pneumonia secondary to a suppurative process in 
the upper respiratory passages, in which particles of infective material 
are inspired and lodge in the bronchioles. 

Purulent pneumonia is rarely met in the course of fibrinous pneu- 
monia, but sometimes occurs as a terminal condition. Abscesses of con- 
siderable size may be formed. 

Hematogenic purulent pneumonia is secondary to suppurative or 
gangrenous processes in other parts of the body, and is a manifestation 
of pyemic infection. It is frequent in puerperal septicemia, in suppura- 
tive osteomyelitis, and like conditions. The micro-organisms are 



DISEASES OF THE RESPIRATORY SYSTEM 



589 



carried by the veins to the right heart, and may first set up malignant 
endocarditis, from which embolism takes place, or they may pass directly 
through the right heart to the lungs. As a rule, the micro-organisms 
in question are either streptococci or staphylococci; but in certain 
specific infections (as typhoid fever) the specific organisms may alone 
occasion purulent pneumonia. 

When large embolic masses reach the lungs occlusion of larger 
branches of the pulmonary artery occurs and hemorrhagic infarcts are 
formed. In the earliest stages these appear as more or less well-circum- 
scribed areas of hemorrhagic infiltration of dark-red color. Very soon 
change of color occurs, and the foci alter to a grayish, then a yellowish, 
color, and finally liquefy, forming suppurative cavities, with irregular 
walls. The lesion at this stage constitutes what clinicians describe as 
abscess of the lung, and though such abscesses may result from fibrinous 
pneumonia or other conditions, the most frequent variety is thai follow- 
ing embolism or thrombosis of the pulmonary artery. The tissue 
around the abscess is intensely engorged and edematous, and not rarely 
quite hemorrhagic. Microscopically, the lesion in the earlier stages 
presents the appearances of a catarrhal and hemorrhagic pneumonia. 
The abscesses frequently break into the bronchi and discharge their 
contents; more rarely rupture into the pleural sacs occurs. The pleura 
itself is intensely inflamed over the embolic areas, and, as a rule, is 
covered with fibrinopurulent exudate. Extensive purulent pleurisy 
(empyema) may occur. 

When the micro-organisms reach the lung in a more disseminated - 
manner they pass at once to the smaller arterioles and capillaries. The 
organisms circulating in the blood are, in all probability, single, but 
when they meet the intricacies of the pulmonary capillary network 
they are arrested. The oxygen present favors agglutination of bacteria, 
especially of the pneumococci. The swelling of the vascular endo- 
thelium by toxic agencies, in all general infections, favors the settling 
of bacteria. 

Embolic infarcts are wanting in such cases, but there is dffiuse 
serous, hemorrhagic, catarrhal, and purulent exudation, which causes 
consolidation of a somewhat gelatinous character. Small foci of suppu- 
ration (miliary abscess) may be seen, and the purulent process may vis- 
ibly extend to neighboring parts of the lung along the lymphatic vessels. 

Terminations. — In either of the above forms, the localized embolic 
or the diffuse, necrosis or gangrene of the pulmonary tissue may occur. 
Occasionally recovery takes place by absorption of the purulent exudate 
or by its discharge. As a rule, the disease is fatal. 

Pleurogenic purulent pneumonia follows intense pleurisy, usually 
of purulent type. Infection of the subpleural lymphatics first ensues, 
and later the purulent process extends into the lung within and around 
these vessels (purulent lymphangitis and perilymphangitis), in the form 
of yellowish streaks or bands, which surround the veins and bronchi 
and follow the interlobular fibrous tissue in various directions. The 
lobules of the lung may be so pushed apart that the term pneumonia 
desiccans is quite applicable. The proper substance of the lung adjoin- 
ing the paths of purulent invasion, and under the pleura, frequently shows 



590 



A TEXT-BOOK OF PATHOLOGY 



the same form of hemorrhagic and purulent pneumonia as occurs in 
the diffuse hematogenic form. 

Associated Lesions. — Widespread pyemic and toxic lesions are 
often found in association with purulent pneumonia, but they are often 
merely coincident results of the same primary disease to which the 
pneumonia owed its origin, rather than the consequences of the purulent 
pneumonia itself. Secondary infections may, however, occur, such as 
malignant endocarditis of the left side of the heart, septic nephritis, 
and the like. 

GANGRENE 

Gangrene of the lung results from the action of putrefactive micro- 
organisms in necrotic areas of the lung tissue. It may be the conse- 
quence # of direct extension of carious conditions of the ribs or other 
adjacent bony structures through the pleura into the lung, or of the 
extension of necrotic processes from ulcers or cancerous disease of 
the esophagus or stomach. In other cases the infective materials reach 
the lung through the inspired air, coming from ulcerative processes in 
the upper air-passages or from without. When foreign bodies lodge in the 
bronchi, or the latter are obstructed by the pressure of tumors or an- 
eurysms, there may be, first, more or less congestion and pneumonic 
consolidation, followed by secondary infection and gangrene. In still 
other instances the infective material reaches the lung through the 
blood. Finally, gangrene is sometimes a terminal process in pneu- 
monia, tuberculosis, and hemorrhagic infarction of the lungs. Certain 
general conditions predispose more or less to it. Thus, in diabetic indi- 
viduals, congestions or pneumonia are prone to terminate in this way, 
and engorgement of the veins or passive hyperemia always renders the 
lung more liable. 

Wessler has lately pointed out the relation of gangrene to abscess 
of the lung and the frequency with which this follows tonsillectomy 
especially when a general anesthetic is used. Acute forms appear more 
frequently in the upper lobes, no matter whether they be caused by 
aspiration or pneumonia, and are preceded by bronchiectasis and 
peribronchitis. Chronic or late abscesses and gangrene arise, more 
especially in the dependent parts of the lung, after pneumonitis, as the 
result of imperfect resolution and fibrotic indurations with retention 
of infective matter. 

Pathological Anatomy. — Gangrene may appear as a circumscribed 
or diffuse process. In circumscribed gangrene more or less extensive 
areas of lung present a dark, reddish, brownish, or even greenish appear- 
ance, and are surrounded by a zone of intense congestion or of pneumonic 
consolidation, often of purulent or hemorrhagic type. The diseased 
part is soft, pultaceous, and foul in odor. Later it may break down into 
a putrid mass, and may discharge through the bronchial tubes, severe 
pulmonary hemorrhages sometimes occurring at the same time. The 
bronchi and the blood-vessels often escape the process, and may pass 
through the gangrenous area without being themselves materially 
affected; but usually the bronchi are penetrated, and the blood-vessels, 
after they become occluded by thrombosis, suffer the fate of the other 



DISEASES OF THE RESPIRATORY SYSTEM 



591 



tissues. The process may extend widely from a single focus, or react- 
ive inflammation may establish a fibrous capsule, and after discharge 
of the gangrenous material through the bronchi, healing by the forma- 
tion of a scar may terminate the disease. 

Diffuse gangrene does not differ much in its general appearances, 
but is less intense and, in general, more widespread. The affected area 
is of a dark-red or greenish-black color, soft and edematous, or some- 
times dry, and has a somewhat fetid odor, as in the circumscribed form. 
Spots of hemorrhagic infiltration and of softening, with formation of 
cavities, may be noted. 

The sputa in gangrene are mucopurulent, of a yellowish-gray or 
brownish color, and intensely fetid. When placed in a conical vessel 
they separate into three layers: the upper frothy, the lower puriform 
and brownish in color, and the middle layer more fluid and yellowish. 

INFECTIOUS DISEASES 
Tuberculosis 

Tuberculosis of the lungs is usually a local process at first, but in 
many cases becomes generalized by subsequent spread of the infec- 
tion. Sometimes the pulmonary disease is from the beginning only a 
part of a general tuberculosis. 

Infection of the lungs occurs through the bronchial tubes (broncho- 
genic tuberculosis), through the blood-vessels (hematogenic tuberculosis), 
or through the lymphatic system (lymphogenic tuberculosis) . 

1. The first of these three modes of infection is probably far more 
frequent than the other two combined. The tubercle bacillus, dissemi- 
nated by the drying of sputa or other infected discharges from tubercu- 
lous patients, is carried directly to the lungs in the inspired air or, more 
rarely, it may lodge in the pharynx, upper air-passages, or bronchi, and 
produce primary tuberculous lesions from which the lungs are second- 
arily affected. Immediate infection of the lungs is more frequent than 
the secondary form. 

2. Hematogenic infection is clearly evident in cases in which a tu- 
berculous disease of some other part (as the bronchial glands, prostate, 
bones, etc.) has become generalized by entrance of the tubercle bacilli 
into the circulation and in which tuberculous lesions make their ap- 
pearance in various parts of the body, including the lungs. Sometimes 
the point of rupture of a tuberculous focus into a vein has been demon- . 
strated. The bacilli entering the venous circulation are carried through 
the right heart to the lungs, and are, for the most part, arrested in 
them. When finely divided in the blood some may pass through the 
pulmonary circulation and may thus be distributed widely through the 
body. In many cases, however, the lungs arrest all the bacilli and be- 
come affected without general tuberculosis. Sometimes perhaps the 
lungs are infected through the vascular channels without pre-existing 
lesions elsewhere. This may occur when tubercle bacilli traverse the 
mucous membranes and enter the circulation without causing a primary 
lesion at the portal of entrance. How frequently this may happen 
cannot very well be estimated, but many facts speak in favor of its 



592 



A TEXT-BOOK OF PATHOLOGY 



not infrequent occurrence. Tuberculosis of the mesenteric glands 
without intestinal lesions is not uncommon, and cannot be explained 
except on the assumption that the bacilli passed through the mucosa 
and into the lymphatics without causing a lesion at the portal of en- 
trance. Other facts (as, for example, the occurrence of primary tuber- 
culosis of bones) indicate that the bacilli may be distributed widely in 
the circulation without local lesions at the places where they entered 
the body. Lung tuberculosis can doubtless occur in the same way, 
and some authorities believe this a frequent mode of infection. In view 
of the demonstrated intercommunicability of human and bovine tubercu- 
losis, the possibility of pulmonary infection from the consumption of 
tuberculous meat and milk and the passage of the bacilli through the 
mucosa of the digestive tract is apparent. 

In some cases of hematogenic tuberculosis the bacilli gain entrance 
to the blood in an indirect manner, as, for example, when a lesion of the 
abdominal or thoracic lymph-glands penetrates the thoracic duct. The 
bacilli carried in the lymphatic stream pass through the thoracic duct 
and eventually reach the blood and are disseminated in the lungs and 
other organs. 

Localized hematogenic tuberculosis of the lungs may occur when an 
old tuberculous lesion of the lung or a caseous bronchial lymph-gland 
penetrates a branch of the pulmonary artery and thus disseminates 
bacilli in the lungs. This mode of occurrence of the disease in the lung is 
rarely observed. 

3. Lymphogenic infection of the lungs is secondary to tuberculous 
pleurisy, tuberculous bronchial lymphadenitis, mediastinitis, etc. In 
these cases the pleural and subpleural lymphatics become infected and 
the process spreads along these channels to the lungs. 

A combination of the aerogenic and lymphogenic routes is possible. 
It is believed that tubercle bacilli may settle on the mucosa of the upper 
air- and alimentary passages, be carried thence to the regional lymph- 
nodes, and finally to the mediastinal or bronchial glands, where they 
may involve the lung by extension or rupture. Still, again, the lymphatic 
channels may combine with the alimentary tract, and, as has been dis- 
cussed under Anthracosis and the Tubercle Bacillus, the organisms may 
reach the root of the lung by the lymphatic chain along the posterior 
midline of the body. This and the direct bronchogenic invasion form 
the principal infection tracts for Koch's bacillus. 

Bronchogenic Tuberculosis 

Larger masses of infective material inhaled in respiration may lodge 
in the bronchi or larger bronchioles and set up tuberculous ulcerations, 
from which smaller particles may be secondarily aspirated into the 
finer divisions of the bronchial tree. And again, perhaps more commonly, 
the tubercle bacilli are inhaled in a state of extreme dissemination, 
and are not arrested until they reach the point of division of the terminal 
bronchioles into the alveolar passages. One of two results may occur 
at this point : either there is set up a limited area of caseous or tuberculous 
pneumonia, or the bacillus penetrates between the epithelial cells with- 
out producing a definite intra-alveolar lesion and causes specific tubercu- 



DISEASES OF THE RESPIRATORY SYSTEM 



593 



lous changes in the peri-alveolar and peribronchial connective tissues 
(miliary tubercles). It has been the occasion of some dispute among 
pathologists to decide which of these processes is most apt to arise when 
the infection occurs through the bronchial tubes. Undoubtedly, both 
kinds of change may take place, and it seems likely that in most in- 
stances there is a mixture of the two forms. When the infective material 
is in great abundance and is particularly virulent, and in cases in which 
the individual is especially vulnerable, caseous pneumonia predominates 
over the formation of tuberculous nodules. On the other hand, a less 
abundant infection or greater resisting power on the part of the in- 
dividual determines a greater liability to the formation of nodules 
and less likelihood of extensive caseous pneumonia. Whichever lesion, 
however, is primary, the other soon becomes associated. Thus, if the 
epithelia of the alveoli are first affected with production of caseous 
pneumonia, the peri-alveolar connective tissues are soon involved, and 
tubercles form in loco, or, by dissemination of the bacilli along the 
lymphatic channels of the peri-alveolar connective tissues, tubercles 
appear at some distance from the first lesion. The alveoli contiguous 
to such secondary tubercles may in the next place become involved in 
caseous pneumonia. When the primary lesion is a tubercle in the peri- 
alveolar connective tissue, the adjacent alveoli in the same manner suffer 
caseous pneumonia. Thus, the disease spreads through neighboring 
lobules and in time affects considerable areas of the lung. 

Degenerative changes soon make their appearance. The areas of 
pneumonia, which began as small foci or as larger areas of lobular tuber- 
culous pneumonia, change their color from a grayish to a yellowish 
color and become completely caseated; while the secondary tubercles 
in the neighborhood, or those which were primarily formed, similarly 
become opaque and lusterless, and finally yellowish by caseation. The 
blood-vessels in caseous pneumonia or in the tubercles are inadequate 
to supply sufficient nourishment to the tissue. In the pneumonic areas 
this is due to proliferative changes in the intima and to direct pressure 
of the exudate, while in the tubercles it is due to hyaline and other forms 
of degeneration, with collapse of the walls. 

Coincidently with the process just described, round-cell infiltration 
and proliferative changes are manifest in the structures surrounding the 
diseased areas. In the case of the areas of caseous pneumonia, infiltra- 
tion and proliferation of the connective tissue of the septa, as well as 
proliferative changes in the blood-vessels of these parts, are observed. 
There is a wide variation in particular instances in the degree of these 
reparative processes, and in general it may be said that the more acute 
the disease, the more apt is degenerative caseation to take place and the 
less likely regeneration to occur. Similar overgrowth and infiltration 
may be seen around the tubercles, and in favorable instances the latter 
may eventually be completely encapsulated or converted into a fibrous 
nodule. In instances in which the reparative processes are very exten- 
sive there may eventually be a preponderance of connective tissue over 
caseous pneumonia or miliary tubercles. 

Varieties. — We may distinguish all of the forms of bronchogenic 
tuberculosis by the name of pneumonic tuberculosis, from the fact that 

38 



594 



A TEXT-BOOK OF PATHOLOGY 



the element of caseous pneumonia is always an important one, and 
separates them sharply from hemogenic and lymphogenic tuberculosis, 
in both of which the formation of miliary tubercles predominates over 
other processes. It must, however, be remembered that in some cases 
of hemogenic tuberculosis the lesion may take the form of a localized 
pneumonic tuberculosis by reason of the fact that the first-formed miliary 
tubercles are soon obscured by a more extensive pneumonic process, 
due either to an overwhelming local dose of bacilli with such a rapid 
infiltration that something resembling an infarction occurs, or to the 
concomitant action of other microbes, pneumococcus for example. 

Three forms of pneumonic tuberculosis are met with: the acute, 
which is frequently spoken of as acute caseous phthisi s, or galloping 
consumption; the chronic, which is also known as Chronic ulcerative 
phthisis; and the form in which fibrous overgrowth predominates, and 
which is, therefore, known as fibrous or fibroid phthisis. While typical 
instances of these forms are quite distinct, there is no sharp dividing line 
separating the groups, and individual forms merge insensibly one into 
the other. 

Acute pneumonic tuberculosis is more common in children than 
in adults. Two elements play a part in its occurrence: first, a high 
degree of susceptibility; and, second, abundant infection with virulent 
bacilli. The latter may be derived from without the body by direct 

inhalation, or may come from the dis- 
charge of older caseous areas in the 
lungs which have broken into the bron- 
chial tubes, or from some focus of 
tuberculosis in the upper air-passages. 

Pathological Anatomy. — This form of 
tuberculosis is lobular, but very fre- 
quently by confluence of the affected 
areas an entire lobe may be involved. 
Either the base or the apex may be 
first affected. On section the lung pre- 
sents a more or less variegated appear- 
ance in the earlier stages, due to the 
Fig. 262.-Bronchogenic tuberculosis formation of minute patches and lobular 
of the lung, showing the involvement areas of caseous pneumonia having a 
of the tissues surrounding the terminal a ra yish appearance, and the coincident 

bronchioles (Birch-Hirschf eld) . * v x- r 

congestion of surrounding portions 01 
the lung tissue. Sections through the lung which cut a terminal 
bronchiole in a longitudinal direction show it more or less filled 
with cheesy exudate and surrounded by peribronchial caseation 
(Fig. 262). Transverse sections give the appearance of a section 
through a large tubercle or an aggregation of tubercles, but the 
lumen of the bronchiole may usually be discovered in the center or 
to one or the other side. Small miliary tubercles may be apparent in the 
edges of the pneumonic patches, and even for some distance around 
them, but the connective tissue involvement is more apt to appear 
as a diffuse infiltration along the peribronchial and perivascular lymph- 
atics than as distinct tubercles. As the process increases the lung tissue 




DISEASES OF THE RESPIRATORY SYSTEM 



595 



becomes more and more extensively involved and uniformly gray or 
yellowish and consolidated (Fig. 263). The cut section is generally 
somewhat granular in the earlier stages from admixture of fibrinous 
exudation in the alveoli; but later progressively increasing caseation and 
softening render the surface of section smooth and moist. Not infre- 
quently complete destruction takes place and cavities are formed. 
These are usually small and present no 
marked tendency to the formation of an 
organized wall, but appear simply as 
necrotic excavations with irregular, 
ragged outlines. The pleura over the 
surface of such a lung is usually in- 
flamed and covered with more or less 
fibrinous or nbrinopurulent exudation, 
and not rarely with an abundant crop 
of tubercles. Sometimes a superficial 
lesion may rupture into the pleural cavity 
and cause pneumothorax or, later, 
pyopneumothorax . 

When the process is less active and 
the infection less abundant, confluence 
of the lobular areas is less likely to 
occur, and there are seen merely dis- 
seminated patches of caseous pneumonia 
scattered through various parts of the 
lung, which is, in general, more or less 
congested. In such instances, too, the 
evidences of reparative change are more 
decided. Complete encapsulation with 
subsequent calcification may ensue, or 
fibrous overgrowth may convert the en- 
tire area into a cicatricial mass. If the 

Cheesy area is simply enclosed with Fig. 263.— Extensive bronchogenic 

fibrous tissue, it may remain quiescent tuberculosis (caseous pneumonia) of 

„ , . -iir j v the base of the lung (Orth). 

for a time, possibly for years, and sub- 
sequently penetrate the enclosing wall and occasion a fresh extension 
of the whole process. 

Chronic pneumonic tuberculosis is the ordinary form of pulmonary 
phthisis. It begins in the apices of the lungs in the great majority 
of cases, though children are as likely to be first affected at the bases 
as at the apices. The apices present areas of low resistance because of 
their short excursion of motion and the slow gaseous interchange. They 
are slightly less vascular than lower lung portions. 

While there is no doubt that chronic phthisis is usually due to infec- 
tion through the inspired air, it must be admitted that occasionally the 
onset of the process is due to infection through the blood or lymphatic 
channels (see p. 591). In the instances of the latter kind there may 
first be established a localized lesion which caseates and penetrates a 
bronchial tube, discharging its contents, and thus leading to widespread 




596 



A TEXT-BOOK OF PATHOLOGY 



bronchogenic infection. The further development of the disease takes 
place in several distinct ways (see below). 

Pathological Anatomy. — When there has been a pre-existing bron- 
chitis, adhesion of the bacilli may occasion tuberculous bronchitis 
with ulceration and secondary involvement of the surrounding tissues. 
More commonly the bacilli lodge in the finer bronchioles or alveolar 
passages, as in acute pneumonic phthisis, and give rise to lobular areas 
of caseous pneumonia, surrounded by tubercles which are formed along 
the course of the lymphatic vessels leading out from the first-formed 
caseous foci. There is a tendency to a constant increase of the area of 
disease by the discharge of caseous material into contiguous bronchi 
and its aspiration into other parts of the lung, and also by dissemi- 
nation of the infection along the lymphatic vessels traversing the 
connective tissue around the blood-vessels and bronchi. Section through 

the lung discloses more or less con- 
solidated tissue of an opaque, gray- 
ish or yellowish appearance, in 
which the bronchi may be seen 
as open spaces or filled with muco- 
purulent liquid. Little distinction 
between caseous pneumonia and 
the tubercles can be made in the 
center of such an area, but at the 
edges, where the process is seen in 
the earlier stages, such distinction 
may be possible. 

At times areas of a fibrinous 
or cellular pneumonia are formed. 
These differ from caseous pneu- 
monia in presenting a granular or 
gelatinous appearance, and in their 
liability to partial or complete 
resolution. The process is sero- 
fibrinous and cellular in character, 
and often, though not always, due 
to secondary infections. 

Unless the process is very rapidly 
ulcerating, reparative processes can be detected quite early, in the 
septa and perivascular tissue. A round and connective tissue cell 
proliferation may be seen in a zone about the advancing lesion, just 
outside the exudate in which epithelioid and giant cells occur; such 
a reactive zone is not seen abutting upon a necrotic area. As the name 
implies, connective tissue reaction is more pronounced than in the 
acute form. 

The degenerative and necrotic processes lead to a most characteris- 
tic lesion of tuberculous lungs — the cavity (Fig. 264) . Cavities are formed 
either through the dilatation of the bronchioles (bronchiectasis), due to 
their ulcerated and weakened condition and to the pressure of retained 
secretions, with subsequent ulceration and breaking down of the sur- 
rounding caseous tissue; or, on the other hand, to liquefaction of caseous 




Fig. 264. — Tuberculous cavity of apex 
of lung communicating with bronchus, as 
shown by rod (from a specimen in the 
collection of Dr. Allen J. Smith). 



DISEASES OF THE RESPIRATORY SYSTEM 



597 



areas not in connection with a bronchial tube. In the latter case, 
however, communication with the bronchi is usually established by 
extension. A single cavity may grow larger and larger by constant ulcera- 
tive processes, in which not alone the caseous tuberculous degeneration 
takes a part, but also active ulcerative changes dependent upon mixed 
infection through inspiration of pyogenic organisms. As a rule, how- 
ever, larger cavities are formed by the confluence of separate smaller ones, 
and there may be found a series of excavations communicating more or 
less extensively with each other (Fig. 265) . The -cavity, or vomica, con- 




Fig. 265. — Chronic phthisis pulmonalis with cavities of left lung; note communicating 
cavities near apex, disseminated miliary tuberculosis of right lung (from a specimen in the 
collection of Dr. G. W. Norris). 

tains a variable amount of ill-smelling, putrid secretion, consisting of 
broken-down cheesy matter, pus-cells, degenerated epithelial cells 
and fibers of elastic tissue, and containing tubercle bacilli, pyogenic 
organisms, and occasionally mould fungi. The walls of the cavity are 
generally formed by reparative fibrous proliferation, and are covered 
with a " pyogenic membrane, " usually darkly pigmented. The inner 
surface is very rough and ribbed by projecting bands. The latter 
represent the trabecule and blood-vessels of the lung tissue, which have 
resisted ulceration more obstinately than the surrounding structure of 
the lung. This resistance may continue to such an extent that the 
blood-vessel is left as a cord passing directly through the center of the 
cavity, although such unusual exposure of a vessel is most often due to 



598 



A TEXT-BOOK OF PATHOLOGY 



the advance of ulceration so rapidly that obliterative endarteritis can- 
not occur. Fortunately the latter process is commonly successful 
in closing the lumen of vessels in the immediate wall of a cavity, other- 
wise fatal hemorrhages would occur from every vomica. Not infre- 
quently examination of the blood-vessels in the wall of the cavity or 
passing through it show small aneurysmal dilatations which result 
from the weakening of the wall by the surrounding necrotic process 
and from the pressure of the blood within. It is from aneurysms of 




Fig. 266. — Reticular fibrosis. (From Norris and Landis: Phipps Institute, Fifth Report.) 

this character that the large and often fatal hemorrhages of the later 
stages of tuberculosis take place, though hemorrhage may also occur 
directly from erosion of blood-vessels without aneurysmal dilatation. 
The smaller hemorrhages of the early stages of phthisis, which occasion 
only a streaking of the sputa with blood, are due to early erosion of small 
vessels of the bronchioles or to capillary ruptures dependent upon 
congestion. 

The reparative processes (connective-tissue formation) in chronic 
pneumonic tuberculosis may cause cessation of the disease when only 



DISEASES OF THE RESPIRATORY SYSTEM 



599 



limited areas of the lung are affected, by surrounding and thus encap- 
sulating the diseased parts, or by complete fibrosis of the areas. These 
changes are dominant in the form next to be described. 

Fibroid Phthisis. — The reparative or fibrous processes which tend 
to counteract caseation and destruction may begin before cavity forma- 
tion or after it. When beginning in the earlier stages the caseous areas 
will be found to present a capsule of more or less well-developed fibrous 
tissue, which may completely surround and separate them from the 
neighboring tissue of the lung. The capsule tends to contract and 
shrink, and the caseous material within may become completely cal- 
careous. In this manner a limited focus of tuberculosis of the lungs not 
infrequently becomes completely arrested. When the capsule is not so 
firm, after a period of quiescence or latency extending over even a 
number of years, fresh extension may begin, the capsule may be per- 
forated, and acute pneumonic phthisis may be established, or the tuber- 
culous process may extend more slowly through the contiguous areas 
as chronic ulcerative phthisis. When the tuberculous lesion is limited 
and consists of minute foci not too closely conjoined, the fibrous tissue 
proliferation may intersperse the lesion so that the whole is converted 
into sclerotic tissue instead of being merely surrounded by a capsule. 

When the lesions have been multiple especially when they involve 
thesepta of the lung, wide fibrous bands may spread through the 
organ and materially deform it. They not uncommonly seem to radiate 
from the hilus but of course may be limited to a lobe if such have been 
the only part implicated. 

The fibrous capsules surrounding the cavities, which have already 
been alluded to, may be of varying prominence. In case of small 
vomica? with pronounced fibrous walls the contraction of the latter may 
almost obliterate the cavities, leaving only narrow and distorted spaces 
containing a small amount of putrid material {cicatrices fistuleuse of 
Laennec). Complete healing of a cavity of notable size probably never 
occurs. When the excavations are of large size the reparative processes 
consist simply in the formation of a thick wall of fibrous tissue, which 
prevents the further extension, for a time at least, of the tuberculous 
process. 

Complications in Bronchogenic Tuberculosis. — Of first importance 
in tuberculosis of the lung is the condition of the pleura. In the acute 
pneumonic form the pleura adjoining the diseased areas is generally 
more or less inflamed and may present considerable fibrinopurulent 
exudation, as in croupous pneumonia. Serous or seropurulent exuda- 
tion may likewise be present, and eruption of miliary tubercles in the 
pleura is not unusual. The same processes may occur in chronic pneu- 
monic tuberculosis or chronic phthisis. More commonly there are found 
simply fibrous adhesions binding the one surface of the pleura to the 
other, especially at the apex. 

Extension of the tuberculous process may also take place directly 
upward along the air-passages, and is due, for the most part, to direct 
infection by the sputa. There may thus occur tuberculous ulceration 
of the larger bronchi, of the trachea, of the larynx, or of the pharynx. 
When the sputa are swallowed, as is especially likely to happen in 



600 



A TEXT-BOOK OF PATHOLOGY 



children, or in adults during sleep, intestinal tuberculosis is apt to occur. 

Finally dissemination of the tuberculous disease through the blood 
is frequent. A caseous area adjacent to one of the veins may penetrate 
the lumen of the vessel and discharge its contents into the circulating 
blood, or may first occasion tuberculous proliferation in the intima of 
the vein or infectious thrombosis, from which the blood is secondarily 
infected. There results general miliary tuberculosis, the tubercles occur- 
ring especially in the spleen, the liver, the kidneys, the choroid coat of 
the eye, or in the membranes of the brain or other serous membranes. 

Acute pneumonia may accompany either acute or chronic pneu- 
monic tuberculosis, and certain authors insist that in practically all 
cases there is more or less mixed infection. This is probably not the 
case, but complicating pneumonia is undoubtedly frequent. In most 
of such cases localized patches of catarrhal bronchopneumonia are seen 
between the caseous lobules; but sometimes a frank fibrinous consolida 
tion may occupy the lower lobe of a lung in which the upper lobe pre- 
sents beginning tuberculosis. Quite frequently there are small areas 
of pneumonic consolidation of fibrinous character in the lobe which is 
itself the seat of tuberculous involvement. Toward the end of life there 
is usually extensive edema of the bases and posterior portions of the 
lungs. 

The heart has interesting relations with tuberculosis of the lungs. 
Early writers called attention especially to the fact that phthisical sub- 
jects frequently present unusual smallness (hypoplasia) of this organ, 
and later attention was directed to the fact that congenital stenosis 
of the pulmonary orifice predisposes to tuberculosis of the lungs. Some 
have claimed that there is an antagonism between cardiac disease and 
tuberculosis. This view is not well founded, though it is probable that 
the chronic congestion of cardiac disease renders the lung somewhat 
less vulnerable to tuberculous infection than the normal lung. Where 
there is a long-standing tuberculous consolidation, hypertrophy, espe- 
cially of the right ventricle, is likely to occur. Tuberculous pericarditis 
may be found in association with tuberculous pleurisy; and tubercles 
may also, though much more rarely, be found upon the endocardial 
lining. The latter are due to infection through the blood. 

Hematogenic Tuberculosis 

This form occurs when a focus of tuberculous disease ruptures into 
a blood-vessel and the infective contents are disseminated in the cir- 
culation. As a rule, hemogenic tuberculosis of the lungs is only a part 
of a general tuberculosis of the entire body. The points from which 
the primary infection may take place are, of course, numerous, but 
caseous lymph-glands of the cervical or peribronchial group, or old 
foci of tuberculosis at the apex of the lung, are perhaps the most fre- 
quent. The organs and structures of the body likely to be involved 
by general hemogenic tuberculosis are the spleen, the liver, the kidney, 
the choroid coat of the eye, the meninges, and, more prominently than 
any other organ, the lungs. In the rare cases in which rupture of an 
old pulmonary focus has occurred into one of the branches of the pul- 
monary artery, only one lung, or but a part of a lung, may be involved. 



DISEASES OF THE RESPIRATORY SYSTEM 



601 



Some writers think that intimal tubercles of the pulmonary artery and 
its branches are the sources of continued infection of the lungs. Atten- 
tion has been previously directed to the probability that in some, if not 
many, cases what appears to be bronchogenic pulmonary tuberculosis 
is, in reality, hemogenic, the bacilli having entered the body at some 
obscure point without causing a lesion at the portal of entrance, and 
having produced a localized lesion in the lung instead of the more typical 
disseminated tuberculosis usually found in hematogenous infections. 

Pathological Anatomy. — The pathological feature of importance 
in hematogenic tuberculosis is the formation of miliary tubercles. These 
appear as gray or translucent areas, the size of millet seeds, around 
and involving the terminal arterioles or capillaries in the intervesicular 
septa. At first they may be so small that the naked eye scarcely dis- 
covers them, and they are so translucent that oblique light is necessary 




Fig. 267. — Miliary tuberculosis of the lung, showing two tubercles with degenerated 

centers. 

to make them appear to view. Later, .they increase in size and become 
more grayish and opaque. "Microscopically, there are the well-known 
characteristics of the miliary tubercle embedded in the perivascular 
connective tissue. These tubercles, however, are prone to distinguish 
themselves from the characteristic tubercles seen elsewhere by their 
more irregular outline and the more irregular arrangement of their com- 
ponent histological elements. When the tuberculous process is particu- 
larly rapid and virulent, giant cells are few in number, and the tubercle 
is composed mainly of proliferated connective-tissue cells of the ordi- 
nary type, some epithelioid cells, and round infiltration cells, all of them 
more or less granular, and the entire nodule surrounded by a zone of 
caseous, catarrhal, or even hemorrhagic pneumonia of the contiguous 
alveoli of the lung (Fig. 268). The tubercles are rarely seen in the stage 
of advanced necrosis, but this may take place in instances of a more 
chronic course in which the bacteria are admitted to the lungs slowly 



602 



A TEXT-BOOK OF PATHOLOGY 



and perhaps in a state of lesser virulence than common. In those in- 
stances of what may be termed " chronic miliary tuberculosis" there may 
be a considerable amount of caseation of the tubercles, and the patches, 
as a rule, become decidedly larger than in the ordinary acute form (Fig. 
268). An explanation of this form of chronic miliary tuberculosis has 
been offered by certain authors, who hold that these are instances of in- 
fection through the thoracic duct and blood-vessels. The infective 
material enters the thoracic duct from caseous lymphatic glands in the 
abdomen or thorax, and is discharged with the lymph into the veins in 
a gradual manner, only a little being allowed to pass at a time. 




Fig. 268. — Miliary tuberculosis. (Norris and Landis.) 



The ordinary and typical acute miliary tuberculosis presents itself 
clinically as an acute infectious disease, running its course rapidly and 
causing early dissolution. The disease is rather a general toxemia than 
a local process, and toxemic changes may be present in various organs, 
such as occur in other infectious and toxemic diseases. The heart, liver, 
the kidneys, and, in general, the parenchymatous structures are prone 
to become degenerated, and when the febrile infection continues there 
may be extensive fatty degeneration. In addition to the eruption of 
miliary tubercles in other organs, to which allusion has already been 
made, there is also involvement of the pleura which belongs properly to 



DISEASES OF THE RESPIRATORY SYSTEM 



603 



the pulmonary process itself, and is simply a continuation of the same 
infection which gave rise to the pulmonary involvement. 

Lymphogenic Tuberculosis 

It is possible for tuberculous infection of the lungs to occur through 
the lymphatic channels in several ways. In speaking of acute miliary 
tuberculosis, particularly of the more gradual type, reference was made 
to the fact that infective material is sometimes carried by the thoracic 
duct from the lymphatic glands of the abdomen and posterior medi- 
astinum, as well as possibly from carious thoracic vertebrae to the 
blood-vessels, and thence distributed through the blood to the lungs as a 
hematogenic infection. Direct infection, however, through the lymphatic 
channels may take place. Thus, tuberculous pleuritis, either primary or 
secondary to tuberculous disease of the vertebrae or ribs, sometimes 
spreads directly into the lung through the lymphatic vessels traversing 
the interlobular connective tissue; and in cases of caseous tuberculosis 
of the peribronchial glands the infective material may be conveyed into 
the lungs either by a reversal of the current of lymph in the vessels run- 
ning to these glands or by direct extension along the lymphatic walls. 
A form of lymphogenic tuberculosis of the lungs may also be referred to 
in which caseous lymph- glands directly perforate the lung tissue, but 
the actual dissemination of the process in the lungs in these cases is 
usually through the bronchial tubes into which the bacilli gain entrance. 

Pathological Anatomy. — It is characteristic of lymphogenic tuber- 
culosis to find small nodular areas which microscopically are seen to be 
more or less characteristic tubercles. These are scattered along the 
lymphatic vessels running in the interlobular septa or surrounding 
the blood-vessels and bronchi. In the instances of lymphogenic tuber- 
culosis secondary to pleuritis suppurative lymphangitis and perilymph- 
angitis (see Pneumonia) are not infrequently associated. 

SYPHILIS 

It has been the occasion of much dispute whether the many forms 
of pulmonary disease attributed to this cause can be really so classified. 
Among such doubtful cases are certain pulmonary consolidations in 
secondary syphilis, and lesions of the lungs in old syphilitics that have 
the superficial appearances oV tuberculosis. Undoubtedly some of 
the conditions attributed to syphilis are cases of tuberculosis, or of some 
other form of pulmonary disease. But there are other varieties which 
can unquestionably be spoken of as syphilitic. Among these are the 
diffuse infiltration of the newborn and the tertiary gummata. 

Diffuse syphilitic infiltration of the lungs is occasionally met 
with in the newborn. As a rule, infants showing this are stillborn. 
It manifests itself as a more or less lobar consolidation and induration 
of the lung tissue. On section, the lung is light gray or almost white in 
color, and completely airless, so that the name pneumonia alba, given 
by older writers, was highly significant. Microscopically, there are 
seen widespread round-cell and spindle-cell infiltration and prolifera- 
tion in the interalveolar and interlobular connective tissues, with more 
or less compression of the bronchioles and alveoli. The epithelium of the 



604 



A TEXT-BOOK OF PATHOLOGY 



latter may be somewhat proliferated and desquamated, and shows a 
tendency to fatty degeneration and necrosis. In some instances the de- 
generative changes do not take place, and the proliferated epithelium 
of the alveoli is massed within the alveolar lumen, and is, for the most 
part, of a cuboidal character. The blood-vessels commonly show 
proliferation of the adventitia as well as of the intima, and may be 
completely obliterated. According to Birch-Hirschfeld, syphilitic fe- 
tuses of the sixth or seventh month sometimes present limited disease 
of this nature, and of such distribution that it is recognized to begin 
as a peribronchial and peri-alveolar infiltration of lobular distribution. 
In this type Spirochcetw pallida; are very numerous. 




Fig. 269. — Syphilis of lungs: a, a, Thickened alveolar walls or stroma; b, partly longi- 
tudinal section of bronchus; c, uninfiltrated alveoli; d, new connective tissue infiltrated 
with small round cells; e, cells lining alveoli; /, artery showing thickened walls; g, des- 
quamated lining cells (Linsley). 

Syphilitic gummata may be associated with the diffuse form of 
congenital syphilis, or may be present in the newborn without the latter 
Gummata are occasionally seen in adults. They are present most 
frequently near the root of the lung beneath the pleura, but may be 
scattered through other parts of the organ. As a rule, the number is 
limited. They appear as more or less rounded nodules of a grayish to 
yellowish color, with more or less fibrous overgrowth surrounding them 
and often radiating from them into the surrounding lung tissue. Central 
necrosis may proceed to such extent that cavities are formed. 

Occasionally the contents of a gumma may be discharged through 
the bronchial tubes, or they may be absorbed and a cicatricial pucker- 



DISEASES OF THE RESPIRATORY SYSTEM 



605 



ing of the lung tissue may mark the place of the former disease. Spiro- 
chcetce pallida can be found, but are not numerous. 

Syphilitic fibrous induration of the lung, so-called, has been 
described, and it seems likely that some of the cases embraced in the 
description are really syphilitic in nature. The process begins, as a rule, 
at the root of the lungs, from which it radiates through the tissue toward 
the pleura. The fibrous tissue, for the most part, surrounds the bronchi 
and blood-vessels (Fig. 269). In another group of cases the process 
spreads from the pleura and occasions the formation of dense bands of 
fibrous tissue passing inward into the lung structure. In still other 
cases the fibroid overgrowth is so diffuse that the appearance presented 
resembles so closely that of pneumonokoniosis that it is practically in- 
distinguishable. It is quite probable that many instances in which 
appearances such as these are met with are not at all syphilitic; but 
the occurrence of changes of this description in association with gum- 
mata, and, again, the occurrence of such changes without gummata in 
undoubtedly syphilitic individuals, make it likely that some at least are 
of this origin and nature. Spirochcetce pallida? are exceedingly difficult 
to find, and only can be found, indeed, where there is a frank infiltrate 
among the fibrous tissue. 

GLANDERS 

Glanders occasionally affects the pulmonary tissue, the infection 
taking place either by inhalation from ulcerated lesions in the nose 
or other portions of the upper air-passages, or, more rarely, by distribu- 
tion of the bacilli through the blood. The lesions are of two kinds. 
There may be merely a grayish or purulent infiltration of a diffuse 
character, with the formation of abscesses and often with associated 
hemorrhagic .infiltration. Considerable areas of the lung may be con- 
solidated in this manner, or the process may be localized and lobular. 
In other cases nodular patches varying from the size of a hemp-seed to 
that of a pea are seen in various parts of the lung. These consist of 
masses of round cells, and show an early tendency to degeneration. 
More or less hemorrhagic and catarrhal inflammation of the alveoli sur- 
rounding these nodules may be present. 

ACTINOMYCOSIS 

Actinomycosis is a rare affection of the lungs. It may result from 
the direct extension of actinomycosis of the lymphatic tissues and cellular 
structures in the anterior or posterior mediastinum, when there are 
formed in the pulmonary tissue fistulous necrotic tracts containing 
more or less cheesy and purulent material, in which the characteristic 
yellowish actinomycosis granules are found. The latter, on microscopical 
study, show the actinomyces. The infection may also take place by a 
gradual descent of the process from the mouth or upper respiratory 
passages along the trachea and bronchi to the lung; or, more commonly 
still, by aspiration of the infective agents. In the latter cases nodules 
consisting of round cells are formed, and present themselves as grayish 
or grayish-red patches varying in size from that of a pea to that of a 
cherry, and showing a decided tendency to fatty degeneration and 



606 



A TEXT-BOOK OF PATHOLOGY 



purulent softening. The surrounding lung tissue is commonly con- 
solidated, and presents the appearances of purulent and catarrhal or 
even hemorrhagic pneumonia. In many cases there is also a manifest 
tendency to productive changes, which lead eventually to the formation 
of more or less fibrous tissue within the alveoli and in the interalveolar 
and interlobular connective tissues. Not rarely this indurative process 
completely surrounds areas of degeneration and softening. Infection 
with streptothrix follows the same general character. 

TUMORS 

The lungs are, comparatively speaking, rarely the seat of tumors, 
though a variety of both primary and secondary growths occur. 

Connective=tissue Tumors. — Small nodular fibromata have occa- 
sionally been observed scattered through the lungs in the peribronchial 
connective tissue, and a few instances of similar nodules of lipoma are 
recorded. Chondroma is more common than either of these, and doubt- 
less takes origin from the bronchial cartilages. Secondary chondromata 
have been observed in cases of chondroma elsewhere. True osteoma is 
rare, but more frequently ossification of sclerotic areas is met with in 
instances of pneumonokoniosis. 

Sarcoma is the most frequent connective-tissue tumor of the lungs. 
The lymphosarcoma form may originate in the lymphatic glands sur- 
rounding the bronchi at the roots of the lungs, from the lymphatic 
nodes surrounding the smaller bronchi within the lungs, from the lym- 
phatic vessels themselves, or from the subpleural or other connective 
tissue of the lung itself. Primary sarcoma is less common than sec- 
ondary. In one form it presents itself as rounded masses of grayish 
or yellowish color lying around the bronchi in the root of the lung. On 
section through this it is seen to consist of more or less enlarged and 
transformed lymphatic glands, and there may be secondary nodules 
scattered through the lung. This form of sarcoma is particularly com- 
mon in pneumonokoniosis, as seen in the fibroid lungs of the cobalt- 
miners of Schneeberg. Primary sarcoma also includes endothelioma, 
which arises either within the lung tissue or from the pleura. The 
lymphatic vessels in the peribronchial tissue become filled with pro- 
liferated cells, and their ramification may be distinctly visible on section 
as a network traversing the pulmonary tissue. Primary sarcoma of the 
spindle-cell or round-cell variety may spring from the subpleural connec- 
tive tissue. Giant-cell sarcoma has been observed. 

Secondary sarcoma is extremely common. It is seen in nearly all 
instances in which metastasis has occurred from a primary growth in any 
part of the body. In these cases there are found well-defined nodules of 
varying size, situated for the most part near the surface of the lung 
(Fig. 271). They are whitish in color and tend to soften. The lung 
tissue between may be congested, and there may even be pneumonic con- 
solidation. Secondary sarcoma of the lung may also occur from direct 
extension of mediastinal sarcoma or of sarcoma in other of the surround- 
ing structures. An interesting type of secondary involvement of the 
lungs by sarcoma or a process resembling sarcoma occurs in "malig- 
* nant lymphoma" or "lymphadenoma," either with or without leu- 



DISEASES OF THE RESPIRATORY SYSTEM 



607 



kemia. These may be considered as allied to generalized lympho- 
sarcoma. The lungs are found to contain small nodules, consisting of 
round cells without stroma or embedded in a more or less reticular 
matrix of stellate and spindle cells. 

Epithelial Tumors. — Carcinoma is practically the only form to be 
considered, though adenoma of the lung has been described. Carcinoma 
of the lung is certainly less frequent than was formerly believed, sarcoma 




Fig. 270. — Sarcomatous of lung, Fig. 271. — Secondary sarcomata of the lung: 
hematogenous in origin, showing dis- the primary growth was attached to the pleura, 
tribution from hilus. 

having been confused with it. Massive cancer may start from the 
mucous glands of the larger bronchi near the root of the lung. The 
tumor is irregular, soft, and tends to ulcerate in the center, forming 
cavities. Secondary nodules within the lung tissue are seen along the 
lymphatic vessels surrounding the bronchi. Primary carcinoma may 
also start from the epithelium of the finer bronchial tubes. The pro- 
liferation soon penetrates the wall of the bronchus and extends along 
the lymphatic vessels in the peribronchial connective tissue. In this 
manner bands of new growth are seen traversing the lung. Occasionally 
squamous-celled carcinoma may originate in the epithelium of the 
terminal bronchioles and alveoli. 

Secondary carcinoma of the lungs is less frequent than secondary 
sarcoma. It may occur by metastasis from cancer elsewhere, and in 



608 



A TEXT-BOOK OF PATHOLOGY 



these instances the appearance of the nodules is much the same as that 
of sarcoma. Secondary cancer of the lung may also result from exten- 




Fig. 272. — Secondary metastatic lymphosarcoma of lung (from a specimen in the collection 

of Dr. Allen J. Smith). 




Fig. 273. — Metastatic carcinoma of lungs from a primary pyloric growth (photographed by 

Dr. Ayer). 

sion of esophageal carcinoma or of cancer of the breast penetrating the 
thoracic walls and pleura. Finally, in carcinoma of the upper respira- 



DISEASES OF THE RESPIRATORY SYSTEM 



609 



tory passages or of the mouth, inhalation of cancerous particles may 
lead to secondary nodules in the lungs, associated at times with areas 
of bronchopneumonia. 

Cysts. — Congenital cysts have been described, but they are probably 
merely dilatations of the bronchi. (See Bronchi olectasis.) Adeno- 
matous proliferation of the epithelial lining of such dilatations may 
take place. Dermoid cysts are rarely encountered. They may dis- 
charge through the bronchial tubes. 

PARASITES 

Besides the specific and pathogenic micro-organisms that have been 
referred to as occurring in tuberculosis, pneumonia, and other infec- 
tious diseases, various forms of bacteria and mould fungi are met with 
as accidental and non-specific parasites. Such micro-organismal collec- 
tions are most frequent in areas of gangrene, in degenerated infarcts, 
and in dilated bronchi or tuberculous cavities. Sarcinse, leptothrices, 
streptothrices, and several varieties of aspergillus have been noted. The 
general term Pneumonomy costs aspergillina is applied to the occurrence 
of the last-named mould fungi in the lungs. Sometimes they are so 
abundant that they are readily discovered in the sputa; and it is likely 
that certain inflammatory conditions of the lungs are directly due to 
such organisms. The clinical course may suggest tuberculosis, and 
pathologically diffuse or irregular consolidation of the lungs may char- 
acterize such cases. (See p. 342.) 

Animal Parasites. — Of the lowest forms of animal life or protozoa, 
the Monas lens, cercomonas, and Paramecium have been observed. 
These are entirely accidental, occurring in cases of gangrene, putrid 
bronchitis, and similar conditions. The class of Vermes furnishes the 
more important parasitic affections of the lungs. The Paragonimus 
ringeri is not infrequent in parts of Asia. It occasions serious hemop- 
I tysis. The Strongylus apri, echinococcus cysts, and Cysticercus cellu- 
losa? are occasionally seen. Linguatula rhinaria has been observed. 

The Pluera 

Anatomical Considerations. — The pleura is a membrane composed 
of fibrillar connective tissue and elastic fibers, containing a rather abun- 
dant network of capillaries. It is lined on the surface with a single layer 
of flat endothelial cells, between which there are openings from the 
pleural cavity into the subpleural lymphatics. The latter form a rich 
network in the subpleural connective tissue and play an important part 
in the pathological processes affecting the pleura. It must be remem- 
bered that the two pleural surfaces are normally in apposition, that is, 
no cavity exists. They move over one another with the movements of 
the chest. There is normally a condition of negative pressure amounting 
to about 5 mm. of mercury in the pleural cavity ; under pathological con- 
ditions, air or fluid, this is changed to a positive pressure. The central 
thoracic tissues, heart, vessels, glands and fibrous tissue, form a partition 

39 



610 



A TEXT-BOOK OF PATHOLOGY 



between the lungs and pleural chambers. This is, however, not rigid 
bending slightly away from the side that develops a positive pressure, 
and thus may compress the lung on the sound side. The latter may under 
this condition lose its negative value and attain a positive one. Some of 
the dyspnea of pleural cases may be thus explained. 

CIRCULATORY DISTURBANCES 

Active Hyperemia. — This arises as the early stage of inflamma- 
tion or as the result of decrease in tension, such as occurs when fluid 
in the cavity is removed. 




Fig. 274.-^Cardiac hydro thorax. A case of rheumatic mitral and tricuspid disease, 
with marked cardiac dilatation, auricular fibrillation, etc., under observation forj[many 
years. Died in a state of anasarca. Body frozen in the recumbent posture. 

The diaphragm is depressed. The effusion reaches to the uppermost limits of the 
pleural cavity. The lung is compressed, and the dilated heart, displaced downward. 

The pericardium contains a small effusion (Norris and Landis). 

Passive hyperemia occurs in various diseases interfering with the 
respiration, and still more intensely in cases in which there is pressure 
upon the azygos veins. 

Petechial hemorrhages may occur when the congestion is intense. 
They are particularly frequent and prominent in cases of death from 
suffocation, but are also seen in various disorders of the blood and hem- 



DISEASES OF THE RESPIRATORY SYSTEM 611 

orrhagic diatheses, such as pernicious anemia, purpura, and intoxica- 
tions of various kinds. 

Hemothaox is the term applied to the presence of free blood in the 
pleural cavity. It may be due to wounds of the chest wall, causing 
rupture of blood-vessels, to fracture of the ribs, and to rupture of aneu- 
rysms into the pleural sac. In some cases the etiology is obscure. If 
the pleura is in a healthy condition and secondary infection does not 
take place, more or less rapid absorption of the blood ensues. When 
infection occurs, secondary inflammations of the pleura and disorganiza- 
tion of the blood result. 

Hydrothorax, or dropsy of the pleural cavity, may be but a part 
of a general edema occurring in chronic kidney or heart disease. It 
is usually bilateral, and the fluid presents the ordinary characteristics 
of a serous effusion. Unilateral hydrothorax is, however, not infre- 
quent in cardiac disease attended with great enlargement of the organ. 
The hydrothorax in such cases is generally right sided, and is probably 
due, according to Fetterolf and Landis, to pressure by some dilated 
segment of heart upon the pulmonary veins which drain those from the 
visceral pleura. The pleura itself is not particularly disordered, but 
very frequently some opacity and loss of luster is noted, and there may 
be edema of the subpleural fibrous tissue. The lungs are pressed back- 
ward toward the root and against the spinal column, and may be con- 
siderably compressed. Unilateral hydrothorax may be due to pressure 
upon the veins of one side by tumors or aneurysm. A small amount of 
serous outpouring into the pleural sacs occurs quite commonly just 
prior to death. The fluid of hydrothorax has the usual characters of 
transudates, low specific gravity, pale color, alkalinity, moderate pro- 
tein content, and very low cell content. 

Chylous effusion in the pleurae is due to obstruction or rupture of the 
thoracic duct or some large lymphatic channel, with the appearance 
of a milky opaque fluid containing fat-droplets. 

Hydrothorax causes compression of the lungs and displacement of 
the other adjacent viscera. The seriousness of the results are in pro- 
portion to the amount of effusion. 

Pneumothorax designates the presence of air in the pleural cavities. 
It may result from rupture of tuberculous vomicae, gangrenous areas, 
softened hemorrhagic infarcts, or abscesses of the lungs, or rupture of 
emphysematous air-vesicles beneath the pleura, allowing egress of air 
into the pleural sac. It may also occur after an empyema has ruptured 
into the lung and established a fistulous communication between the 
pleural sac and the bronchioles. Very rarely it is due to a penetrating 
wound of the chest. The pleural sac may be more or less tensely dis- 
tended with air and the mediastinal tissues pressed toward the other side. 
If these structures have been stiffened by inflammation, they may not 
compress the so-called sound lung but under ordinary conditions both 
lungs are compressed. That on the first affected side shrinks toward the 
vertebral column as a grayish brown, airless mass while the secondarily 
compressed lung is deep red and may be edematous. The collapse of the 
affected lung has been ascribed to an attempt to preserve the temperature 
constant of the blood, by contraction of the essential muscle of the organ. 



61-2 



A TEXT-BOOK OF PATHOLOGY 



The pleura itself may present no abnormality, and the air may be ab- 
sorbed; but very frequently infection takes place, and purulent exudation 
from the pleura collects in the sac. The condition is then spoken of /as 
pyopneumothorax. The neighboring organs are often greatly displaced, 
particularly the heart, the diaphragm, and the liver. In left-sided 
pneumothorax the heart may be pushed far to the right of the sternum, 
and when the right side is affected the liver may be pushed downward 
considerably below the ribs. The condition of the air inlet and outlet has 
something to do with the outcome of the condition. If the fistulous chan- 
nel from a lung cavity permits air only to pass to the pleura with inspira- 
tion, and does not permit its escape upon expiration, the accumulation 
will continue. The air, once within the cavity, may remain in about the 
original amount, or it may undergo variations when a free ingress and 
egress is afforded. Pneumothorax may be circumscribed by pleural 
adhesions, and then is termed " closed." 

INFLAMMATION 

Inflammation of the pleura, or pleuritis, is designated by the 
clinical name pleurisy. 

Etiology . — It may result from local or from general causes. Among 
the local causes the most important are extension of inflammation 
from the lungs in the various forms of pneumonia, in gangrene and tuber- 
culosis; extension from pericarditis or mediastinal diseases, and extension 
from inflammatory affections of the spine, of the ribs, or of the chest 
walls. Less directly, peritonitis, hepatic abscess, and other abdominal 
affections may occasion pleuritis by extension, and in rare cases perfora- 
tion of esophageal or gastric ulcers, or abscess of the spleen or liver, 
may be the cause. 

In the group of cases due to general causes the pleural inflamma- 
tion is the result of infection or intoxication involving the pleura through 
the blood. Thus, in pyemia and septicemia, in rheumatism and in 
other acute infectious diseases, and in Bright's disease, acute inflam- 
mation of the pleura is not uncommon. Cold and traumatism have 
long been regarded as important causes, but their action is doubtless 
only a predisposing one, the immediate cause being some infection for 
which the traumatism or the exposure to cold has paved the way. 

It is to be remembered that the pleura is made up of a visceraFand a 
parietal layer, two smooth surfaces bathed by a small quantity of lymph, 
sliding over one another in respiratory movements. While the incep- 
tion of pleurisy may be localized the piocess soon spreads over both 
surfaces. It is, of course, possible to have an acute or chronic pleurisy 
localized by reactive connective-tissue growth, as when due to a purely 
local cause, such as an indented broken rib. 

The commonest micro-organismal excitants of pleurisy are strep- 
tococci, pneumococci and tubercle bacilli. The former two usually enter 
the pleural sac by extension along the septa of the lung to form foci under 
the visceral pleura through which they can penetrate; hematogenous 
transfer, in the absence of pulmonary consolidation, can occur. In the 
instances secondary to tuberculosis of the lungs, as well as sometimes in 
cases of primary pleurisy without affection of the lungs, tubercle bacilli 



DISEASES OF THE RESPIRATORY SYSTEM- 



613 



are discovered. It is important to note the fact that in many instances a 
small and unrecognized tuberculous lesion of the lung may be the source 
of infection in cases which seemingly are primary pleurisies due to ex- 
posure, cold, etc. It would, however, be a mistake to assume that all of 
such apparently primary pleurisies have a tuberculous etiology. During 



A 




mttms: , L. • . . _ ... _ * J 

Fig. 275. — Transverse section of lung from a case of pleuropneumonia, showing great thick- 
ening of the pleura (A) and consolidation of one of the lobes of the lung (B). 

the acute stages it is usually difficult to obtain positive cultures but as the 
fluid becomes more turbid, bacterial findings are more often definite. 
Still later negative cultures are obtained because the fluid tends to steri- 
lize itself in favorable cases. With the tubercle bacillus the case is 
different, it being always difficult to find the organisms without animal 
injection. In rare instances staphylococci, the pyocyaneus bacillus, the 



614 



A TEXT-BOOK OF PATHOLOGY 



Bacillus coli communis, the typhoid bacillus, the bacillus of anthrax, and 
other organisms have been found. 

Pathological Anatomy. — Several forms of pleuritis may be recog- 
nized, though one of these merges into the other, and a single case may 
pass from one into another form at its various stages. It is well, however, 
to separate these stages as distinct forms, since many cases maintain a 
uniform character throughout. The forms are the fibrinous, serofibrin- 
ous, purulent, and hemorrhagic; after any of these forms there may be 
left chronic pleural thickening or adhesions of a fibroid character. 

Fibrinous pleuritis begins with congestion and loss of luster of the 
pleural surface, after which there soon follows exudation of a fibrinous 
character, forming a thin, whitish pellicle on the surface. This may be- 
come yellowish and increase in thickness, so that the pleural surfaces 
become agglutinated, and when separated present an appearance lik- 
ened to the appearance of two pieces of buttered bread separated after 
having been pressed together (bread-and-butter pleurisy). This process 
may be confined to small areas of the pleura, or it may be quite universal. 
Sometimes it is limited to the reflections of the pleura separating the 
lobes of the lung. 

Microscopically, the exudate consists of fibrils or flakes or granular 
masses of fibrin more or less infiltrated with round cells. Beneath this 
the endothelium of the pleura is found to be somewhat thickened by 
proliferation and some of the cells are detached. Two conflicting views 
have been entertained regarding the origin of fibrin formation in the 
pleura. According to one, the deposit is purely exudative and the endo- 
thelium is in nowise involved, being found intact under the fibrinous 
layer. According to the other view the fibrin formation is partly de- 
pendent upon destruction of endothelial cells. Whichever explanation 
is correct, there almost always remains a broken layer of endothelial 
cells in the acute and subacute stages. This may be removed when ad- 
hesions and chronic thickening obliterate the membrane. The con- 
nective tissue beneath the endothelium and the subpleural connective 
tissue are infiltrated with round cells and the blood-vessels are hyper- 
emic. In favorable cases and when the process has been slight a gradual 
reabsorption of the exudate takes place, and the integrity of the pleura 
may be restored completely. When the exudate has been more exten- 
sive and the agglutination of the pleural surfaces has been considerable, 
new blood-vessels from the capillaries of the pleura penetrate the fibrinous 
exudate, fibroblastic cells develop from the older connective-tissue cells, 
and gradually organization takes place, so that the adjacent layers of 
pleura are bound together by connective tissue, the fibrinous exudate 
gradually undergoing absorption and disappearing. The adhesions thus 
formed are at first delicate and quite cellular, but are later converted into 
dense, sclerotic bands. When fibrinous pleurisy occurs repeatedly, as in 
tuberculosis of the lungs, and is not sufficiently extensive to cause adhe- 
sions, the surface of the pleura may become thickened and opaque in 
spots fiom proliferation of the connective tissue. In this way consider- 
able chronic thickening of the pleura may ensue. 

Serofibrinous pleuritis may be simply a further stage of the fore- 
going form, though in many instances it begins almost at once as a 



DISEASES OF THE RESPIRATORY SYSTEM 



615 



serous exudation into the pleural sac. The liquid is heavier than drop- 
sical fluid and contains flakes and shreds of fibrin. Microscopically, 
it is found to oontain white and red blood-corpuscles in small numbers, 
and occasionally detached endothelial cells. Sometimes the number of 
red corpuscles increases considerably, and there may be a gradual transi- 
tion to the hemorrhagic form of pleuritis. The amount of liquid varies 
from a few cubic centimeters to several liters ; and the pleura itself shows 
a more or less extensive coating of fibrinous exudate. 




Fig. 276. — Pyothorax. Large post-pneumonic empyema. The whole right pleural 
cavitywas filled with a thick purulent exudate, some of which may still be seen adherent to 
the. costal pleura. The right lung is completely atelectatic, and has been compressed into 
a small fibrous mass. The heart is displaced to the left, and the diaphragm, downward. 
The left lung in its lateral aspect is compressed by the heart (Norris and Landis). 

Purulent pleuritis, empyema, or pyothorax, is always the result of mi- 
cro-organismal infection. The process may begin as a purulent pleuritis, 



616 A TEXT-BOOK OF PATHOLOGY 

or as a primary serofibrinous pleurisy, secondary pyogenic infection 
occurring either from within the body or through infected aspirating 
instruments from without the body. It may supervene upon pneu- 
monia, tuberculosis, or abscesses in adjacent parts (subdiaphragmatic). 
When a transition of the latter kind occurs the exudate is seen to be- 
come more and more turbid; the number of pus-corpuscles gradually 
increases until the liquid is quite purulent. Spontaneous discharge of 
empyema may occur and most frequently takes place through the 
lung and bronchi. More rarely rupture occurs through the chest walls 
anteriorly between the ribs. When rupture has occurred through the 
lung and bronchi the fistulous communication may remain open and 
pneumothorax may ensue. 

The pleura in empyema shows more or less abundant granulations, 
which in case of discharge of the liquid serve eventually to unite the 
costal and pulmonary pleura by firm fibrous adhesions. During the 
early course of the condition there are almost invariably formed definite 
adhesions between the layers, a free pyothorax, that is, without pockets 
or separated collections of pus, being exceedingly rare it it ever occurs. 
Loculi may occur between lobes, over the diaphragm limited by the out- 
lines of the lower lobe, or at indifferent places over the chest; the most 
important for complications and difficult for surgery is the pocketing of 
pus along the anterior mediastinum. The adhesions thus formed make 
it difficult to remove all the exudate either by nature or by surgery. 
Occasionally the pus may be completely absorbed, or it may undergo 
gradual inspissation, remaining as a more or less cheesy detritus, which 
may finally become calcareous. Such terminations, however, are rare. 
Again, the adhesions may surround an area of much compressed lung and 
enclose the exudate over this area. Thus, we have encapsulated pleurisy. 
In the healing of empyema, retracting scars are common, with the result 
that the lungs, chest wall, or both are distorted. 

Hemorrhagic pleuritis is generally the result of tuberculous infec- 
tion or of malignant disease of the lungs and pleura. Pleuritis may 
also take a hemorrhagic form in old and cachectic individuals, or in 
persons suffering from scurvy, purpura, and similar diseases. As a 
rule, the liquid is serous, with considerable admixture of blood, but in 
tuberculous and malignant pleuritis it is sometimes well nigh pure 
blood. 

Chronic Pleural Thickening. — This term is used to include cases of 
thickening of the pleural membrane following various forms of acute pleu- 
risy, and also cases of a progressive productive character. To the latter 
alone the term chronic pleurisy is, strictly speaking, applicable. In either 
case the pleura is thickened by fibrous overgrowth, sometimes unifoimly, 
at other times in the form of localized thickenings or adhesions. The 
subpleural pulmonary tissue may become implicated. Eventually, the 
thickened pleura contracts, and if adherent to the chest wall may cause 
retractions. The pulmonary tissue is compressed and the bronchi not 
rarely become distorted. In either primary or secondary chronic pleu- 
ritis there may be a total obliteration of the pleural cavitjr. The pleura 
becomes thick, opaque, and is poorly supplied with blood-vessels. Car- 
tilaginous or calcareous change may occur. 



ISEASES OF THE RESPIRATORY SYSTEM 



617 




"a 



J 



Fig. 277. — Late purulent pleuritis, empyema, showing at (a) the active polynuclear 
exudate which at (6) is mixed with fibrinous strands. The zone (c) shows organization 
of the exudate with many capillaries and the appearance of young fibroblasts. The 
remnants of the pleural and subpleural connective tissue, thickened and vascularized, are 
shown at (d), while area (e) is the lung with thickened and broken septa. 



6.18 



A TEXT-BOOK OF PATHOLOGY 



Associated Lesions in Other Parts. — Though pleuritis is frequently 
the result of acute or chronic affections of the lung, it often occasions 
secondary disorders in the latter organ. The subpleural lymphatics 
are commonly distended with cells, and the inflammatory process may 
extend for considerable distances along these channels into the inter- 
lobular septa of the lung. In empyema the resulting purulent lymph- 
angitis and perilymphangitis lead to striking pathological appearances 
(see Pneumonia). The lung also suffers from direct pressure in serous 
and purulent pleuritis. If the compression to which it is Subjected is not 
relieved by absorption of the liquid or by its removal by aspiration, the 
alveolar epithelium degenerates and proliferative inflammation takes 
place in the connective tissue, so that a permanent contraction of the 
lung results. The removal of the liquid at this stage is not followed by 
the return of the lung to its proper size and function. On the contrary, 
the removal or absorption of the liquid in these cases, especially when 
they occur in young children, causes a sinking in of the ribs and curvature 
of the spinal column, and the heart and other adjacent organs may be 
permanently displaced. Most remarkable deformities of the chest may 
occur. Less extensive contraction of one side of the chest, or displace- 
ment of the heart, may result from the contraction of bands of adhe- 
sions, without marked collapse of the lung. 

Pathological Physiology. — Acute pleurisy occasions marked local 
symptoms, beginning with sharp pain on the side affected. This is 
usually due to the local inflammation and rubbing of the affected parts. 
There may, however, be extensive neuralgic pains radiating from the 
center of infection. With the development of effusion, the pain, as a 
rule, subsides, as does also the irritative cough which attends the first 
stage, but shortness of breath develops in correspondence with the 
amount of effusion, due to compression of the affected lung and pressure 
upon the opposite one. The margin of safety in the respiratory surface is 
very great for considerable distortion and pressure may be compatible 
with life. Very extensive effusion in the chest may, however, cause even 
more marked pain and tenderness than dry pleural inflammation. The 
infection in simple pleurisy seems to be a mild one, as fever and constitu- 
tional symptoms are rarely marked. Sometimes the temperature is a 
fluctuating one, and sweating and constitutional depression further 
suggest suppuration, though the effusion is purely serous. Irregular 
fever and constitutional symptoms of the kind indicated are habitual in 
empyema. 

INFECTIOUS DISEASES 

Tuberculosis of the pleura, or tuberculous pleuritis, may be either 
primary or secondary. Cases of the former are comparatively rare. 
In most instances the pleural disease is secondary to tuberculosis of the 
lungs or to tuberculosis of other adjoining parts. Hematogenic infec- 
tion may occur under the same conditions as hematogenic infection of 
the lungs, and frequently the lungs and pleurae are studded with miliary 
tubercles at the same time. 

When the pleural disease is secondary to tuberculosis of the lungs 
the appearances vary considerably. In many cases small gray or yellow 



DISEASES OF THE RESPIRATORY SYSTEM 



619 



tubercles are found in the subpleural connective tissue and in the pleura, 
and the surface may be coated with fibrinous exudate, while the cavity 
of the pleura may be more or less distended with serofibrinous, hemor- 
rhagic, or purulent liquid. The tuberculous tissue is not infrequently 
associated with anthracotic pigmentation and it is common to find a 
zone of black pigment along a lymph channel in the center of which a 
tubercle rests. Also in the form apparently stretching out into the pleura 
from mediastinal glands, the lymph nodes and the streaks of infiltrate 
are mixed with pigment. Not rarely the liquid effusions are reabsorbed 
and dense adhesions are formed, or great thickening of the pleura results. 
The adhesions found at autopsy in healed cases or in those persons who 
have partially fibrotic pulmonary lesions are thus formed. Sometimes 
considerable calcification of the thickened pleura and of the inspissated 
exudate is the terminal result. The tubercle bacilli are often difficult to 
demonstrate in the liquid, even by injections into animals, though they 
may be present in the pleura itself. 

Syphilis of the pleura is a doubtful condition. Fresh pleuritis may 
be found in the neighborhood of a syphilitic gumma; and there are cases 
of considerable pleural thickening in syphilitic persons in which the 
disease may possibly be syphilitic, though in these cases, as in similar 
indurative conditions in the lungs, there is considerable doubt as to the 
essential nature of the disease. 




Fig. 278. — Endothelioma of pleura. 



TUMORS AND PARASITES 

Tumors of the pleura are comparatively rare. Fibromata and 
lipomata are occasionally seen as small nodular masses in the serous or 



620 



A TEXT-BOOK OF PATHOLOGY 



subserous coat of the costal or visceral pleura. Chondromata and even 
osteomata have been observed. More frequently calcification and ossi- 
fication of portions of the thickened pleura take place after pleuritis. 




Fig. 279. — Endothelioma of pleura: the pleural cavity was distended with effusion, and 
the lung was compressed and invaded by secondary nodules. 




Fig. 280. — Microscopical section from Fig. 279. 

Primary sarcoma may spring from the subpleural connective tissue, 
and, according to Coats, is especially common in children, and is most 
frequently of the spindle-cell variety. Primary endothelioma of the pleura 



DISEASES OF THE RESPIRATORY SYSTEM 



621 



(Fig. 278) has been studied by a number of investigators and has been 
referred by some to a proliferation of the surface endothelium, by others 
to a growth from the subserous lymphatics. In a case under the observa- 
tion of one of us it presented itself as a more or less uniform thickening of 
the pleura of one side, involving the diaphragmatic reflection in particu- 
lar. The cavity was filled with hemorrhagic fluid and there were some 
nodular enlargements on the surface (Figs. 279 and 280). This is the 
usual appearance presented. Metastasis may occur in the lung beneath 
the diseased pleura, or even in more distant parts. There is a tendency 
for pleural endothelioma to be accompanied by fibrosis, and oftentimes 
adhesions are seen. 

Secondary tumors of the pleura may occur by metastasis or by direct 
extension. In the former manner sarcomata and carcinomata sometimes 
involve this structure; by the latter method of involvement mammary 
tumors and new growths of the mediastinum, the ribs or other adjacent 
structures may extend to the pleura. 

Parasites. — Echinococcus cysts may originate in the subserous con- 
nective tissue of the costal or the visceral pleura, and may rupture into 
the pleural cavity. Psorospermise have been found in pleural effusions. 
The dysenteric ameba has been found in the pus of empyema following 
hepatic abscess. 



CHAPTER V 



DISEASES OF THE GASTRO -INTESTINAL TRACT 
The Mouth 
< congenital abnormalities 

The most frequent defects in the development of the mouth are 
cleft palate and harelip. In the former of these the entire hard palate 
may be divided, generally to one side of the middle line; and there may 
be associated harelip and fissure of the soft palate. Anteriorly, the 
division occurs between the superior maxillary bone and the inter- 
maxillary bone, the fissure of the lip being also to one side and often 
extending into the nostril. The soft palate is divided along the middle 
line, and the uvula may be separated into lateral halves. The lip may 
be cleft on both sides, so that there is a small central portion connected 
with the septum of the nose and separated from the lateral portions of 
the lip. Harelip is more frequently unassociated with cleft palate. 

Complete absence of the lips, or unusual shortness, especially of the 
upper lip, excessive largeness of the mouth by extension of the fissure 
outward toward the ear, and imperfect development of the lower jaw- 
bone, are rare congenital conditions. 

Macrocheilia (large lips), macroglossia (large tongue), and ankylo- 
glossia (tongue-tie) are congenital malformations. 

CIRCULATORY DISTURBANCES 

Anemia of the mucous membranes of the mouth is seen in cases of 
general anemia, and is often one of the most striking evidences of that 
condition. It is particularly noticeable in the lips. 

Hyperemia. — Active hyperemia occurs in the early period of various 
inflammations, or as a forerunner of some infectious diseases not local- 
ized to the mouth ; while passive hyperemia is met with as the result of 
obstruction of the circulation in pulmonary and cardiac diseases. 

Hemorrhages in the form of small petechia occur in purpura and 
other hemorrhagic diseases, and sometimes in infectious fevers. 

INFLAMMATION 

Inflammation of the mucous membrane of the mouth is termed 
stomatitis; inflammation of the tongue is designated by the name 
glossitis; since they are usually associated and present the same pathology, 
no separation will be made. 

Catarrhal stomatitis may result from direct irritation by hot liquids 
or chemical substances, or may occur in depressed conditions of the 
general system, possibly as a consequence of infection. It is more com- 
mon in children than in adults. The mucous membrane of the mouth 

622 



DISEASES OF THE GASTROINTESTINAL TRACT 



623 



is red and usually covered with considerable liquid exudation. When 
the inflammation is intense, small vesicular cysts may form from dis- 
tention of the mucous glands, and even localized erosions may appear. 
When the inflammation has continued for a long time, or has been re- 
peated, there may form upon the surface silvery white, slightly elevated 
spots, which result from a hyperplasia of the epithelium, a form of kera- 
tosis. This condition has been designated by the name of leukoplakia. 

Mild catarrhal conditions of the mucous membrane ol the mouth 
are especially common on the tongue, the epithelium of which con- 
stantly desquamates. In the course of gastro-intestinal and other dis- 
eases the desquamation may be more active, the cells, however, being 
retained upon the surface. Portions of food and bacteria cling to the 
masses of desquamated cells, and in this manner the whitish or brownish 
furring of the tongue so commonly met with in various diseases is formed; 
a similar process, modified by dessication, is seen in sordes of the lips in 
febrile patients. Sometimes the heaping of epithelial cells takes place in 
localized areas, and extends in peculiarly irregular patches, which, from 
their resemblance to maps, have given rise to the term "geographical 
tongue." In chronic cases the whitish spots of leukoplakia alluded to 
above are formed. 

During certain infections, notably pneumonia, it is common to find 
a vesicular eruption, herpes labialis, upon the lips which may dry and 
leave crusts, while the congestion of the tongue known as strawberry 
tongue is suggestive of scarlatina and Koplik's spots are almost pathog- 
nomonic of measles; these are all mild forms of inflammation. 

Aphthous stomatitis occurrs in children under conditions of mal- 
hygiene and debility, or as a result of gastro-intestinal and other dis- 
eases. Local irritation often plays an important part. There appear 
in the mucous membrane, especially of the lower lip and gums, small 
whitish spots lying upon an inflamed base. Usually these are separated, 
but sometimes confluence occurs, though there is rarely extensive 
spreading. The whitish membrane covering or constituting the spots 
is composed of degenerated epithelium, and sometimes of fibrin, so that 
the term "croupous stomatitis" may in some cases be applied. The 
lesions are superficial and rarely lead to actual ulceration. It has been 
held that the preliminary lesion is a vesicle; this, however, does not 
appear to be frequent, and is certainly not essential. 

Foot-and-mouth Disease.- — A similar affection occurs in animals, 
particularly in cows, sheep and goats, and is designated foot-and-mouth 
disease. This condition is contagious, and considerable epidemics 
have occurred among persons drinking the milk of infected animals. 
The specific cause is unknown; the virus is ultramicroscopical and filter- 
able. The process is one of hyperemia and thickening of the corium 
with vesicle formation in the lowermost layers of the rete. These may 
rupture and form shallow ulcers. 

Bednar's aphthae are small ulcers found in the mouths of sucking 
infants and situated at the lateral portions of the palate over the ends 
of the pterygoid processes, on other parts of the hard palate, or occa- 
sionally on the soft palate. They are probably caused by traumatism 
occurring in the act of sucking. 



624 



A TEXT-BOOK OF PATHOLOGY 



Ulcerative stomatitis may be met with in various parts of the mouth, 
especially in the gums. In young children it is frequently the result 
of malnutrition and lack of cleanliness of the mouth. Various sapro- 
phytic micro-organisms normally found in the mouth may, under suit- 
able conditions, aid in the production of ulcerative stomatitis. Pyogenic 
cocci may also play a part in its etiology. In various cachectic diseases, 
particularly in scurvy, the gums become soft and spongy and tend to 
ulcerate. Mercurial and other forms of poisoning may lead to extensive 
ulcerations. Deeper ulcerations are found upon the sides of the tongue 
or the inner part of the lip in cases of injury due to the sharp edges of 
broken or carious teeth. Ulcerative stomatitis may be secondary to 
necrotic conditions of the bones or suppurative inflammations about the 
roots of teeth. Ulceration beneath the tongue is met with in many cases 
of whooping-cough, and is due to the irritation of the teeth in the 
paroxysms of coughing. 

In ordinary cases of ulcerative stomatitis the gums at the junction 
with the teeth become reddened and soft, and may present hemorrhagic 
infiltration. Later, the epithelium of the surface. is destroyed and open 
ulceis result. Considerable suppuration may occur, and the teeth 
may be loosened and dislodged. 

A form of disease about the necks of the teeth and secondarily 
involving the gums has been termed pyorrhea alveolaris. The process 
is one of cementitis and pericementitis with a separation of the cemen-, 
turn from the lining of the alveolar socket. The cementum is thus 
deprived of its nourishment normally supplied by this peridental mem- 
brane. The discharge of pus from the gums surrounding the teeth gives 
the disease its name. It has been ascribed to infection with spirochetes, 
anaerobes, and amebse, especially the Endamceba buccalis. The impor- 
tance of the last is strengthened by the fact that pyorrhea is improved 
by the use of emetin. This condition has been viewed by some as a 
focal infection from which, as a source, bacteria and their products are 
swallowed or transferred by the blood to other organs, and there set up 
intoxications or infections. Thus, arthritis deformans, chronic adenop- 
athy, and aspiration pneumonia are supposed to arise sometimes. 

The method of origin of pyorrhea alveolaris is probably that tartar 
collects upon the teeth down to the gingival margin, below which food 
particles collect and infection occurs. This process, having at best a 
very limited outlet, turns to a purulent inflammation, leading to gingivi- 
tis and retraction of the gums. 

Another ulcerative process affecting the mucous surfaces within the 
buccal and pharyngeal cavities has probably some relation to Vincent's 
angina since in the discharges one may find spirochetes and fusiform 
rods. It has appeared sporadically, and epidemically especially in the 
late war, when it received the name of "trench mouth;" other names are 
spirochetal gingivitis and stomatitis, spirochetosis of the mouth. The 
lesion appears as shallow continuous ulcerations around the teeth, 
extending to the tongue and lateral buccal wall; the edge is commonly 
marked by a whitish line without which is. a zone of congestion. Infor- 
mation of its histological pathology is lacking but it should not differ 
greatly from Vincent's angina. There is no unanimity of opinion as to its 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



625 



cause but the good effect of the use of arsenical preparations would seem 
to strengthen the belief that spirochetes are at the bottom of it; it is 
at times associated so definitely with frank Vincent's angina of the tonsil, 
and the lesions are so similar when this specific ulceration is absent, that 
it is highly probable that the two are the same. Its occurrence is much 
favored by poor teeth, bad personal hygiene and insanitary surroundings. 

Pseudomembranous stomatitis is most frequently due to the action 
of the bacillus of diphtheria, and is, therefore, strictly speaking, diph- 
theria of the mouth. It is usually secondary to pharyngeal diphtheria, 
but may occur primarily upon the lips or other parts of the mouth. In 
some cases of aphthous stomatitis the lesion is, in reality, a pseudo- 
membranous one. 




Fig. 281. — Case of noma (Children's Hospital). 



Phlegmonous stomatitis is more common in the lips than in other 
parts of the mouth, and may be the result of traumatic injuries with 
intense infection, or a secondary condition after facial erysipelas or 
other cellular inflammations of the face. The lips and cheeks may be 
greatly swollen, and suppuration may occur, forming abscesses which 
tend to rupture into the mouth. A chronic form of inflammation of the 
deeper tissues of the lips may lead to hypertrophy. This is especially 
common in the upper lip as the result of long-standing coryza or 
eczema. 

Gangrenous stomatitis, or noma, affects the mucous membrane 
of the cheeks, and occurs in ill-nourished children, especially after 
measles and other iniectious fevers. There is formed a sloughing ulcer 
on the inner side of the cheek, and inflammatory induration involving 
the entire thickness of the cheek. The skin at first presents a dark-red 

40 



626 



A TEXT-BOOK OF PATHOLOGY 



or bluish discoloration, and later extensive destruction (gangrene) may 
occur (Fig. 281). The pathological changes are those of a rapid necrosis 
of all the tissues, and micro-organisms of suppuration and sapro- 
phytes are usually present. Pseudodiphtheria bacilli have been found 
in some cases. Various spirochetes have been observed. The most 
common finding is a micro-organism belonging to the necrosis bacilli, 
but its pathological importance is not established. Putrefactive 
changes cause a fetid odor. Intense septic infection and intoxication' 
generally attend. 

Milder forms of gangrenous stomatitis affecting the gums around 
carious teeth are occasionally observed. 

Associated Conditions in Stomatitis. — In many cases the inflam- 
mation may extend from the mucous membrane of the mouth poste- 
riorly to the pharynx. Very commonly the lymphatic glands of the 
neighborhood are involved, with enlargement of the submaxillary or 
even the cervical glands. In some cases, especially in mercurial stoma- 
titis, the salivary glands are coincidently or consecutively swollen and 
inflamed. Increased flow of saliva (ptyalism or sialorrhea) is a fre- 
quent symptom. In intense cases, especially in gangrenous stomatitis, 
parenchymatous degenerations of other organs may result from general 
toxemia. 

Glossitis. — Superficial catarrhal inflammations have been referred to. 
The tongue may be involved in the vaiious forms of stomatitis and shows 
similar changes. More extensive inflammations of the tongue, leading 
to parenchymatous glossitis, may result from injuries, especially when 
accompanied by infection. The entire organ may in these cases be 
swollen, and there is round-cell infiltration with a tendency to suppura- 
tion. Localized parenchymatous glossitis with ulceration may occur 
from injury by carious teeth. 

Hemilateral glossitis, sometimes attended with the formation of 
herpetic vesicles, is occasionally observed, and is probably dependent 
upon disease of the chorda tympani nerve. 

ATROPHY AND DEGENERATIONS 

Atrophy of the muscles of the tongue and cheeks may occur in 
association with nervous diseases (bulbar palsy) . Physiological atrophy 
of the gums follows loss of the teeth in old age. 

Degenerations of the mucous membrane usually accompany in- 
flammations. 

Under the name of nigrities, or black tongue, is described a form of 
hypertrophy of the papillae of the tongue with pigmentation. The 
dorsum of the tongue may be covered with a hair-like coating of dark- 
brown or blackish color. The cause of this affection is obscure. 

INFECTIOUS DISEASES 

Thrush, or parasitic stomatitis, is met with in young children, 
and is due to the action of a micro-organism known as O'idium albi- 
cans. There are formed upon the mucous membrane white patches 
resembling curdled milk, and varjdng in size from mere points to large 
areas. These tend to coalesce and to spread. The mucous membrane 



DISEASES OF THE GASTEO-INTESTINAL TRACT 



627 



is reddish and inflamed. The back and sides of the tongue and the inner 
parts of the cheeks are favorite seats. Microscopically, the white coating 
is composed largely of mycelial threads of the parasite, with which are 
mingled degenerated epithelial cells and generally also other micro- 
organisms, notably micrococci. The process may extend to the pharynx, 
and sometimes as far as the bronchi or the stomach, through the larynx 
and esophagus. 

Tuberculosis of the mouth may be primary or secondary. The 
latter is especially frequent at the root of the tongue, and is secondary to 
tuberculosis of the larynx or pharynx (Fig. 282). Small nodular masses 
of tubercles are formed, and tend to undergo cheesy degeneration, 



forming ulcerated areas. Primary tubeiculosis leading to ulceration may 
occur upon the lips or upon the tongue as a result of direct inoculation, as 
in the kissing of a tuberculous person. Nodular masses are formed, which 
at first present themselves as papillary elevations, but subsequently 
undergo characteristic necrosis. Tuberculous ulcers are usually irregular 
or undermined, and the bases are more or less caseous and infiltrated by 
tubercles. The injury of the tongue by the teeth, and the favorable soil 
offered for the retention and multiplication of the micro-organisms in 
carious teeth, may play a part in the causation. 

Lupus of the face may extend to the mouth. It is distinguished by 
the associated cicatrization. Secondary carcinomatous change may 
occur in the base of the lesion (lupus carcinoma). 

Syphilis is most frequently secondary, occurring in the form of 
mucous patches upon the lips or tongue, or as more elevated condylo- 
mata, which in healing cause irregular contractions or whitish or opaline 
thickenings of the mucous membrane. A simple syphilitic catarrhal 
angina may occur. Gummatous infiltrations may appear in a localized 
form or as irregular involvements. On the dorsum of the tongue, their 
commonest seat in this organ, they produce deep, ragged excavations. 
They are usually deep seated and, on healing, fissuration and deformity 
may result. The tongue is the most frequent seat. The primary 
syphilitic lesion (chancre) resulting from direct inoculation is occa- 
sionally observed upon the lips, tongue, or pharynx. 

Actinomycosis affects the tongue, gums, and jaw-bone, and is char- 
acterized by a slowly infiltrating process with a tendency to necrosis 




Fig. 282. — Tubercle of the tongue (Karg and Schmorl). 



628 



A TEXT-BOOK OF PATHOLOGY 



and suppuration, in which the alveolar processes of the jaw-bone are 
generally attacked. The lesion in the mouth may be insignificant, 
while the secondary involvement of the cheeks or of the lymphatic 
glands below the jaw and in the neck may be extensive (Fig. 283). 




Fig. 283. — Actinomycosis of the cheek (Illich). 



Leukemic Stomatitis. — In acute leukemia ulcers of the mouth 
are frequent at the onset and throughout the disease. The gums may 
present an ulcerated appearance resembling that seen in scurvy. Con- 
siderable necrosis and hemorrhagic infiltration are common. Nodular 
infiltration of the adenoid tissues at the base of the tongue and in the 
pharynx also occur in acute leukemia, but more commonly in the chronic 
form. 

TUMORS 

Papillomatous growths of the mucous membrane are occasionally 
observed. Fibroma, lipoma, myxoma, and even chondroma are rare forms 
of tumors of the submucous tissue of the tongue or other parts of the 
mouth. Not rarely they are congenital. Lymphadenoma or lympho- 
sarcoma may occur at the root of the tongue, where it takes origin from 
the lymphatic follicles or the lingual tonsil. Sarcoma of other parts of 
the mouth is rare, excepting as an extension from sarcoma of the jaw- 
bone and other parts. 

Epithelioma or carcinoma is the most important new growth of the 
mouth, and in nearly all cases is of the squamous-celled variety. The 
favorite seats are the lower lip, usually toward one side of the mouth, 
and the tongue, it appears as an irregular nodular elevation which 
tends to ulcerate upon the surface and spread to adjacent structures. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



629 



Metastasis usually occurs to the submaxillary and cervical lymphatic 
glands. 

The name " epulis" is a clinical term applied to tumors arising from 
the alveolar process. Sarcoma and endothelioma are the commonest 
forms. 

Cystic formations, due to agglutination of the mouths of the mucous 
glands, are met with upon the tongue and lips. 

Cysts are especially frequent beneath the tongue, at the sides of the 
frenum. These have been termed ranula, and are formed by the dilata- 
tion of the ducts of the small mucous glands. At times ranula may be 
a cystic dilatation of a duct of the sublingual salivary gland or that of a 
submaxillary gland. Ranula is usually found as a rounded or elliptical 
tumor which may fill the floor of the mouth and displace the tongue 
backward and upward. The contents consist of somewhat gelatinous 
albuminous liquid. They may be due to stenosis of the excretory duct 
by inflammation or blocking by a stone. Cysts may arise at the base 
of the tongue from the remains of the thyroglossal duct, and it is common 
to find thyroid-like acini surrounding them; more solid masses of thyroid 
tissue are found at times displaced to this location. The cysts of thyro- 
glossal duct origin have ciliated epithelial lining. 

Hemangioma, both of the telangiectatic and cavernous varieties, is 
occasionally seen, but a more important tumor is lymphangioma, affecting 
the tongue and lips and giving rise to the conditions known as macro- 
glossia and macrocheilia. In these conditions there is a uniform enlarge- 
ment of the tongue or lips, and on section distended lymphatic spaces 
more or less filled with liquid and round cells are detected. Such en- 
largements are usually congenital, and are especially met with in cretins. 

Angiomata of sarcomatous or carcinomatous nature have been seen 
in the tongue. 

The Teeth 

Anomalous Development. — Unnatural largeness or, on the con- 
trary, lack of development is frequently observed. Complete absence 
of the teeth has been noted. Numerical increase or decrease is frequent. 
Delay in the eruption of the teeth and irregularity in their formation 
occur in rachitis; and a form of maldevelopment of the upper central 
incisor teeth of the permanent set is observed in cases of congeni- 
tal syphilis (Hutchinson 7 s teeth) . The characteristics of this condition 
are the wedge shape of the teeth, the cutting-edge being smaller than the 
crown, and the concave notching of the cutting-edge (see Fig. 119). 
Hutchinson's teeth are not entirely peculiar to congenital syphilis, being 
sometimes seen in rachitis. 

Caries of the teeth results from malnutrition, digestive disturbances, 
and lack of cleanliness. Micro-organisms which lead to acid fermenta- 
tion contribute to the causation by forming acids which dissolve calcium 
salts, soften the enamel, and occasion fissures through which other 
bacteria (bacilli and micrococci) may gain entrance into the channels of 
the dentin. The soft teeth of pregnant women are due to the reduction 
of calcium which is being given to the fetus. 

The carious process consists in a gradual disintegration of the 



630 



A TEXT-BOOK OF PATHOLOGY 



enamel and dentin, with the formation of more or less granular detritus 
in which bacteria are abundant. The process may penetrate to the 
pulp of the teeth and set up a secondary inflammation, or pulpitis. 

Inflammation of the pulp of the teeth may occur in association 
with caries, or sometimes independently. The pulp becomes reddened 
and swollen, and may present hemorrhages and, later, suppuration. 
The inflammatory process tends to spread through the roots of the teeth 
to the tissues surrounding the roots and to the alveolar peiiosteum. 
Abscesses may thus be formed about the teeth, and may spread to the 
tissue of the gums (alveolar abscesses), eventually rupturing upon the 
surface, or penetrate the antrum of Highmore. When the inflamma- 
tion is less active there may be ostitis leading to caries and sequestrum 
formation in the alveolar process by which the teeth become loosened. 
If the root canal is open from the crown to the apex, extension to the bone 
may not occur but in its place a granulating hypertrophy of the pulp may 
cause an inflammatory mass to fill up the carious cavity; cystic growths 
are sometimes seen also (see below). 

Tumors from the teeth may be divided into neoplasms and cysts. 
The former arise from the enamel organ and dentin, possibly at times from 
the cement substance. Adamantinoma probably emanates from the 
enamel organ, therefore being an epithelial tumor, and presents irregular 
masses of imperfect enamel, containing cysts. The microscopic picture 
is of strands of elongated cells, arranged in star-like manner in the center. 
Degeneration of this tissue leads to cystic formations. Odontoma arises 
from the enamel or dentin and appears as multilobular firm or cystic 
masses on the lateral teeth. These growths preserve at times the minute 
appearance of the dentin but may look like sarcoma or fibroma. 

Sarcomata and fibromata may spring from the pulp during the develop- 
ment of teeth or from the connective tissue about the roots; and poly- 
poid outgrowths (hypertrophied granulations) from the pulp may be met 
with in association with caries of the teeth and pulpitis. 

The most important tumor is the giant-celled sarcoma of the alveolar 
process of the jaw. This is known by the name of "epulis," though, 
strictly speaking, the term is applied rather to the situation than to the 
kind of tumor. Extensive enlargements of the jaw-bone and destruction 
of the surrounding tissues may ensue but these growths are not usually 
very malignant. 

Cysts are met with in the alveolar processes, and arise from the pri- 
mary follicles in which the teeth are developed. These may contain 
epithelium and teeth. There are also cystic tumors of the teeth-sockets 
from the periosteum of the jaw-bone. The so-called root cysts probably 
always have an inflammatory origin in a subacute or chronic pulpitis. 
In the overgrowth of the pulp some strand of epithelium is folded in and 
proceeds to develop into a cavity containing serous or mucinous liquid. 
Epithelium, usually squamous, lines the cyst but no teeth are found. 

The Pharynx and Tonsils 

Congenital Malformations. — There may be many minor anomalies 
in these structures but the only one of practical importance is that arising 
from incomplete closure of the branchial clefts. Such defects are seen in 



DISEASES OF THE GASTROINTESTINAL TRACT 



631 



diverticula in the pharynx, either blind or communicating with the exte- 
rior and, when their internal and external ends are closed, there may be 
cysts of this region; teratomata and carcinomata have been reported in 
them. 

CIRCULATORY DISTURBANCES 

Anemia of the soft palate and other portions of the pharynx occurs 
in general anemia and in cases of phthisis or other wasting diseases. 
The mucous membrane may be decidedly pallid. 

Active hyperemia or congestion occurs in the beginning states of 
inflammation and when irritants have been in direct contact with the 
mucous membranes. 

Passive hyperemia is seen in heart disease, emphysema, phthisis, 
and other chronic pulmonary affections. In these cases the mucous 
membrane is dark red, and not rarely becomes somewhat edematous. 

Edema of the pharyngeal tissues is found in association with in- 
flammatory affections or in angioneurotic states, and may occasion con- 
siderable stenosis. 

Hemorrhages may be the result of direct injury, as in the swallowing 
of fish-bones and the like, or may occur in the form of petechia in pur- 
pura and other hemorrhagic diseases and in intense infections (small-pox, 
septicemia) . 

INFLAMMATIONS 

Catarrhal pharyngitis, or angina, may affect the entire lining mem- 
brane of the pharynx, or may be limited to the tonsils or other parts. 
It results from direct irritation by hot liquids or chemical substances, 
from exposure to cold, and particularly from infections. Angina, or 
sore throat, is met with in many of the infectious feveis, or may appear 
as an independent infection. 

The mucous membrane presents a bright-red color, is somewhat 
swollen, and covered with tenacious exudation composed of mucus and 
desquamated cells. Small vesicular elevations may form, and after the 
rupture of these, erosions or even superficial ulcers are sometimes seen. 
Occasionally there are hemorrhagic extravasations. 

A form of catarrhal pharyngitis, known as herpetic angina, is analo- 
gous to herpes of the skin, and may accompany facial or labial herpes. 

Chronic catarrhal pharyngitis is met with in persons who use the 
voice excessively, especially in the open air. It may also result from the 
abuse of tobacco or alcohol. The posterior wall of the pharynx and the 
pillars of the soft palate are particularly involved. The mucous mem- 
brane is swollen in the earlier stages, but later becomes atrophic, and is 
marked by slight granular elevations, which are either hyperplastic 
lymph-follicles or distended mucous glands. The veins in the sub- 
mucous tissue are enlarged, and are visible through the atrophic mucous 
membrane as tortuous channels. Chronic hyperplasia of the tonsils 
and chronic laryngitis are frequently associated. 

Phlegmonous pharyngitis may result from wounds of the pharynx, 
or may be associated with intense infections, such as pseudomembranous 
tonsillitis and pharyngitis, particularly the forms due to streptococci. 



632 



A TEXT-BOOK OF PATHOLOGY 



It may result from pustular pharyngitis in small-pox, or from glanders 
of the pharynx. Phlegmonous tonsillitis sometimes extends to the peri- 
tonsillar tissues as far as the retropharyngeal wall. 

The soft palate, uvula, arches, or other parts affected are swollen and 
tensely distended. There may be congestion or deep cyanosis and ede- 
matous exudation. The usual termination is suppuration, but sometimes 
gangrenous necrosis ensues. General septicemia is frequently the result. 

Retropharyngeal Abscess.— This condition may occur secondarily 
after traumatic or infectious pharyngitis as above described. Phleg- 
monous pharyngitis primarily affecting the retropharyngeal tissues may 
be due to caries of the cervical vertebrae; occasionally it occurs in the 
infectious fevers in consequence of embolism, or infection of the deep- 
seated lymphoid nodes of the pharynx. 

Pseudomembranous pharyngitis may be caused by the Mycobac- 
terium diphtheria, in which case the disease is diphtheria, or it may be 
due to a variety of other micro-organisms, or to irritating gases, steam, 
and like causes. Non-diphtheritic pseudomembranous pharyngitis is 
especially common as a complication of scarlatina, measles, and other 
infectious diseases, and seems in these cases to be caused by the Strepto- 
coccus pyogenes. The appearance of the throat may be identical with 
that observed in diphtheria, but extensive necrosis is more common, 
while typical pse.udomembranes are less frequent. 

The mucous membrane and the underlying parts, especially the 
tonsils, become greatly swollen and edematous, and subsequently suffer 
necrotic changes. 

There is formed upon the surface of the throat a whitish or yellowish 
patch, or several patches, which tend to coalesce and extend from the 
region of the tonsils to the pillars of the fauces and the uvula, or to the 
mouth, nose, or larynx. The pseudomembrane is quite firmly attached 
to the mucous membrane, and cannot be removed without tearing away 
part of the underlying tissues. Microscopically, the deposit is found to 
consist of granular or fibrillar fibrin entangling more or less degenerated 
leukocytes and epithelial cells. In the deeper layers intense congestion 
and round-cell infiltration are observed; in the superficial strata de- 
generated cells and detritus, together with masses of bacteria, are con- 
spicuous. 

The neighboring lymphatic glands, notably those below the angle 
of the jaw, enlarge and may suppurate, and sometimes extensive cellu- 
litis and suppuration of the floor of the mouth (Ludwig's angina) occur. 
There are intense systemic intoxication and infection, and secondary 
lesions are frequently developed in various organs (nephritis, myocardi- 
tis, etc.). The non-diphtheritic forms of pseudomembranous pharyn- 
gitis may be distinguished from the diphtheritic forms, in typical cases, 
by the greater intensity of the local (necrotic) processes, the earlier and 
more marked involvement of the local lymphatic glands, and by the 
greater tendency to nephritis; but, unfortunately, atypical cases are very 
common, and an absolute diagnosis can be made by bacteriological 
study alone. 

Tonsillitis may be a part of a general pharyngitis, or it may occur 
as an independent affection. Several varieties are described. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



633 



Catarrhal tonsillitis results from the same causes as catarrhal phar- 
yngitis in general, and presents similar appearances. The tonsils are 
usually somewhat enlarged. 

Lacunar or follicular tonsillitis occurs from similar causes, and may 
involve the normal tonsil or one affected by chronic hypertrophy. The 
surface of the tonsil is marked with small white or yellowish spots, into 
which the end of a probe may be inserted. These are the lacunae or 
crypts distended with masses of epithelial cells more or less degenerated. 
Bacteria of various kinds may be found in the contents of the lacunae, and 
doubtless play an important part in the etiology. Staphylococci, strep- 
tococci, pneumococci, tubercle bacilli, and the bacillus of diphtheria 
have all been observed. The latter two forms may be present merely 
as accidental associations, but may possibly 
play an etiological part. Ulceration may occur 
in the walls of the lacunae, and the surface of 
the tonsil may be considerably broken down. 
In other cases , the bacteria may penetrate the 
tonsil at the bottom of the lacunae, and 
phlegmonous tonsillitis, or quinsy, may result 
(see below). The contents of the lacunae may 
be discharged upon the surface, and may adhere 
for a time as a yellowish-white caseous pellicle, 
resembling diphtheritic pseudomembranes in 
appearance. In other cases the contents of the 
crypts are retained, undergo inspissation, and 
may even calcify. A certain amount of catar- 
rhal pharyngitis may be associated, but the follicular ulcers are rarely 
seen beyond the tonsils. 

Phlegmonous tonsillitis, abscess of the tonsil, or quinsy, may be 
the result of simple catarrhal or of follicular tonsillitis, or may be asso- 
ciated with phlegmonous inflammation of other parts of the pharynx. 
One or both of the tonsils may be affected. Redness and swelling are 
noted in the earlier stages, but later the mucous membrane is pallid 
or even yellowish. Microscopically, diffuse round -cell infiltration and 
eventually focal collections leading to abscess formation are detected. 
The peritonsillar tissues may be involved, and spreading phlegmonous 
inflammation results. Rupture may take place into the pharynx, or the 
ulceration may extend outward, causing discharge upon the neck at the 
angle of the jaw. The internal carotid artery may be perforated. . 

Enlargement of the submaxillary and cervical lymphatic glands 
is commonly observed. General septicemia of mild type is not infre- 
quent; myocarditis, endocarditis, and nephritis may result. The asso- 
ciation of tonsillitis and rheumatism has occasioned much discussion. 
It is very probable that rheumatism frequently follows tonsillitis, the 
latter being the first effect of micro-organismal invasion, which eventu- 
ally causes rheumatism. 

Chronic tonsillar hypertrophy may result from repeated attacks of 
simple catarrhal or of follicular tonsillitis. The lymphatic constitution 
or status lymphaticus is a factor of importance. The tonsils are en- 
larged, usually irregularly so, and are harder than normal. On section 




B 



Fig. 284— Crypts in 
cases of tonsillitis: A, Acute 
lacunar; B, chronic hyper- 
trophic: a, .surface epithel- 
ium; b, accumulated con- 
tents of crypt; c, lymphoid 
follicles surrounding crypt 
(Kaufmann) . 



634 



A TEXT-BOOK OF PATHOLOGY 



the connective-tissue reticulum and septa are found increased, and the 
lymphoid follicles are likewise hyperplastic. Hypertrophy and distor- 
tion of the gland frequently obstruct the outlets of the crypts thus 
providing places for bacterial colonization, favoring repeated acute 
attacks and thereby establishing a vicious circle, resulting in continuous 
chronic inflammation. Retention and calcification of the contents of the 
crypts are particularly common in the lacunar tonsillitis of hypertrophic 
tonsils. Chronic hypertrophy of the tonsils very often occurs in rachitic 
or badly nourished children in association with hyperplasia of the lingual 
tonsil and nasopharyngeal adenoid tissues — the clinical adenoids. Dis- 
tinct evidences of inflammation are wanting in such cases, and the 
condition seems rather a form of simple hyperplasia of the lymphoid 
structures. 

Pathological Physiology. — Acute tonsillitis may occasion only 
local symptoms, such as pain, difficulty in swallowing, etc., but in many 
cases there are general symptoms — fever, disturbances of appetite, etc. 
The latter vary in severity according to the particular infectious cause 
of the disease. 

A chronically enlarged tonsil probably always contains bacteria, 
and this may constitute a focal infection, whence bacteria may be lib- 
erated to cause damage elsewhere. The streptococci of the tonsils 
have been suspected of responsibility for chorea, arthritis deformans, and 
other subacute infections. Chronically diseased tonsils have been found 
to contain a toxic substance, which when absorbed excites antibodies 
like a parenterally introduced protein, and acts as a protoplasm poison. 
The glands containing streptococci seem to contain most of this poison. 
This may aid in the production of the above diseases. 

PRESSURE NECROSIS 

This condition occurs upon the anterior and posterior walls of the 
pharynx, opposite the cricoid cartilage. It is met with in marantic 
persons occupying a dorsal decubitus, and is caused by the backward 
pressure of the cricoid cartilage against the opposite vertebra. The 
mucosa becomes necrotic, and more or less extensive ulcerations are 
formed. Complete perforation of the pharyngeal wall sometimes occurs. 

INFECTIOUS DISEASES 

Diphtheria of the pharynx usually begins in the mucous mem- 
brane covering the tonsils, and spreads to the pillars of the fauces, to 
the uvula, the posterior wall of the pharynx, the cheeks and tongue, the 
posterior nares, or to the laiynx. It rarely invades the esophagus, but 
may sometimes extend along this structure as far as the stomach. 

The specific cause is the Mycobacterium diphtherice (see Diphtheria, 
p. 299). The characteristic lesion is a pseudomembrane, which is formed 
on the surface and within the mucous membrane. This first appears as a 
grayish or yellowish-white pellicle, more or less firmly attached to the 
mucosa; it spreads rapidly, and may cover the whole of the pharynx in a 
day or two. In other cases the disease progresses slowly or remains quite 
limited. The underlying tissues become swollen by inflammatory 
infiltration (cellular and edematous), and swallowing and breathing 



DISEASES OF THE GASTROINTESTINAL TRACT 



635 



may then be greatly obstructed. When the pseudomembrane is re- 
moved from the surface a raw and more or less necrotic base is exposed. 
Microscopically, the surface of the pseudomembrane is found to consist 
of a mass of debris/often containing micrococci and other bacteria, as well 
as the specific organisms, in great numbers. Somewhat more deeply the 
membrane is composed of a fibrinous reticulum or masses of fibrin en- 
tangling degenerated epithelial cells and leukocytes. Still more deeply 
the tissues of the pharynx are found intensely congested and infiltrated 
with round cells. In the late stages of the disease extensive necrosis of 
the mucosa and submucosa may occur. 

In some cases diphtheria may undoubtedly present the lesions of an 
ordinary lacunar tonsillitis, and the clinician may be unable to deter- 
mine the nature of the disease. 

Associated Conditions. — Some enlargement of the lymphatic glands 
at the angle of the jaw is usual, and exceptionally this may terminate 
in suppuration. Lesions of the internal organs, especially the heart and 
kidneys, are not infrequent, and disease of the peripheral nerves is a 
common sequel (see Diphtheria, p. 302). 

Vincent's angina is a mildly infectious disease characterized by 
superficial ulceration upon which a lightly adherent pseudomembrane 
lies. The process usually begins upon or near the tonsils and spreads 
slowly; it is a superficial ulceration of the epithelium, while in the corium 
there is a moderate round-cell infiltration. The fusiform bacilli, and the 
spirilla probably growing from them, are found in the membrane and on 
the base of the ulceration (see page 358). 

Pharyngomycosis Leptothricia. — This condition is met with 
on the tonsils, and less frequently the pillars of the fauces, uvula, and 
other parts of the pharynx. It occurs in persons of lowered vitality, 
and seems to be caused by the Leptothrix buccalis, a form of bacterium 
very commonly met with in the collections around the necks of the 
teeth. The lesions present themselves as milky-white and somewhat 
chalk-like outgrowths arising from the tonsillar crypts and the mucous 
glands. These are often tightly adherent, but occasion very little 
inflammation of the surrounding tissues. Microscopically, the thread- 
like parasite is found in abundance. 

Tuberculosis may occur in the pharynx in the form of subepithelial 
tubercles, which break down and occasion more or less extensive ulcera- 
tions. 

Tuberculosis of the tonsils may be primary or secondary. In the 
former case infection probably occurs from the invasion of the crypts by 
tubercle bacilli; this condition is doubtless more common than has 
generally been supposed. Secondary tonsillar tuberculosis usually 
follows tuberculosis of the lungs or larynx. In either case there are 
formed in the tonsils small tubercles which rapidly increase in size, fuse, 
and subsequently undergo caseous change. Discharge of the caseous 
matter upon the mucous surface is not unusual, and occasions ulcer-like 
formations. Secondary infection of the cervical and submaxillary 
lymphatic glands is not infrequent. 

Syphilis may occur in the pharynx in the form of the primary 
lesion or chancre, as simple catarrhal angina, as mucous patches, or as 



636 



A TEXT-BOOK OF PATHOLOGY 



gummata. The last are prone to undergo ulceration with secondary 
cicatrization. Extensive distortion of the pharyngeal structures may 
be the result of the scar formation. 

Glanders and lepra sometimes invade the pharynx. 

Typhoid ulcers are occasionally met with. 

TUMORS 

Among the tumors of the pharynx, fibroma, lipoma, and papilloma 
are occasionally found on the soft palate, uvula, or tonsils. Of the 
malignant tumors, sarcoma of the tonsils is most important. It is 
usually of the lymphosarcomatous variety, and is rapid in growth and 
highly destructive. Epithelioma may occur at the base of the tongue, 
in the soft palate, or tonsils. Other varieties of cancer are rare. 

Polypoid tumors of the nasopharynx and hyperplastic adenoid 
growths of the same situation frequently extend downward into the 
pharynx proper. 

The Salivary Glands 

Inflammation of the salivary glands affects the parotid most fre- 
quently. 

Parotitis may be the expression of an independent infection (mumps) ; 
or may be secondary to various infectious diseases, such as typhoid 
fever, typhus fever, or pyemia. Parotitis sometimes occurs in associa- 
tion with diseases or injuries of the abdomen or pelvic organs. A reflex 
or "sympathetic" inflammation has been assumed as the cause of the 
parotid disease by some, but recent investigation seems to indicate 
that in all cases the real cause is infection through the duct. 

The specific cause of mumps has not been isolated (see page 373). 
The infection probably occurs through the parotid duct, and in some 
instances inflammations of the mucous membrane of this duct have 
been found to precede the parotitis. The gland is swollen and tensely 
distends its capsule. The inflammatory exudate is probably largely 
serous, as it may be absorbed and removed in the course of a very short 
time. The disease scarcely ever terminates in suppuration. Orchitis 
is an occasional complication, and may be followed by atrophy of the 
testes. 

The secondary parotitis occurring in the course of various infectious 
diseases is characterized by a marked tendency to abscess formation, 
and at all stages of the affection round-cell infiltration is conspicuous. 
After the formation of an abscess perforation may take place upon the 
cheek or into the mouth, and sometimes salivary fistula? (see below) are 
established. Chronic induration of the gland may remain after attacks 
of inflammation. Chronic parotitis may also result from certain intoxi- 
cations (lead, mercury, iodid of potash) or may occur in chronic nephritis 
or syphilis. Mikulicz described a form of simultaneous enlargement 
of the parotid, submaxillary, and lachrymal glands. The etiology is 
unknown. 

The submaxillary gland is occasionally affected with the parotid, or 
independently, in mumps. The sublingual gland rarely becomes in- 
flamed. 



DISEASES OF THE GASTROINTESTINAL TRACT 



637 



Angina Ludovici, or Ludwig's angina, is a septic inflammation of 
the tissues of the floor of the mouth surrounding the submaxillary gland. 
It may result from carious processes at the roots of the teeth, or from 
infection of the submaxillary lymphatic glands in the course of various 
infectious diseases, particularly scarlet fever. The most frequent 
termination is abscess formation, with perforation externally or into 
the mouth. Occasionally rapid necrosis or gangrene results. Many 
different organisms have been found, but to none is ascribed any specific 
importance. The characteristic of this affection is the density of the 
infiltration, there being almost a wooden hardness. The parts are dark 
red. 

Tumors. — The parotid gland is more frequently the seat of tumors 
than the other salivary glands. Benign tumors, such as fibroma, lipoma, 
or chondroma, are rare. The most common new growth is the so-called 
"mixed tumor," a neoplasm consisting of irregularly arranged cellular 
strands resembling gland acini, surrounded by tissue like cartilage or by 
fibrous and mucinoid tissue; cystic areas occur in them. Some of the 
mixed tumors are said to be endotheliomata, others are described as basal 
cell epitheliomata, but the decision is difficult because of the atypical 
growth of the glandular acini. They appear as well outlined, firm, 
resilient, multilobular masses, the cross section of which varies with the 
predominating element — cartilaginous, myxoid, or cellular. While these 
tumors tend to recur after removal, they are not actively malignant. 
Adenoma and carcinoma are occasionally primary. 

Diseases of the Salivary Ducts. — Salivary fistulce may result from 
traumatic injuries or from the perforation of abscesses. They most 
frequently affect the duct of the parotid. 

Concretions composed of phosphate and carbonate of calcium are 
occasionally observed, and may lead to obstruction of the ducts. 

Cystic dilatation of Steno's or Wharton's duct, or of those of the 
sublingual glands, may be due to concretions or to inflammatory proc- 
esses at the mouths of the ducts. Oval or elliptical tumors are formed, 
and contain transparent, viscid liquid. Such cysts belong to the group 
of conditions designated as ranula, but more frequently this is due to 
obstruction of the small mucous glands beneath the tongue. 

The Esophagus 
congenital defects 

Occasionally the esophagus is double, being divided into two parts 
by a septum. Complete absence of the esophagus may occur in certain 
monstrosities; more frequently there is partial absence of the lumen 
about the middle of the tube. The lower end of the esophagus in such 
cases communicates with the trachea, while the upper end terminates 
as a blind pouch. The intermediate defective portion may be repre- 
sented by a fibromuscular cord, or may be entirely wanting. Fistulous 
communications may pass from the side of the neck to the upper end 
of the esophagus or pharynx. They are due to incomplete closure of 
the branchial clefts. 



638 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Anemia may be due to general anemia; active hyperemia, to the 

irritation of hot liquids or chemicals. 

Passive congestion results from diseases of the heart or lungs, or 
from portal cirrhosis of the liver. In the latter condition large varicosi- 
ties may be established in the lower end of the esophagus, due to the 
communications between the left coronary vein of the stomach, the 
esophageal veins, and vena azygos. Hemorrhage may occur from these 
dilated veins, as they lie close beneath the mucous surface. 

INFLAMMATIONS 

Catarrhal esophagitis is characterized by hyperemia and desquama- 
tion of epithelium, with very little liquid secretion. It may be due to 
the ingestion of irritating acid or alkaline liquids, to scalding, or occa- 
sionally to direct traumatic irritation. Superficial erosions are some- 
times met with. 

Chronic catarrhal esophagitis is found in cases of passive conges- 
tion continued for a long time, and particularly in alcoholics. The 
mucous membrane is thickened and irregularly pigmented. Occasionally 
erosions are met with, and more commonly areas of hypertrophy of the 
mucosa. 

Pseudomembranous esophagitis may result from extension of 
pharyngeal diphtheria or pseudomembranous pharyngitis, or it may be 
primary in rare instances. 

Ulcerative esophagitis may occur as the result of pustular eruption 
in small-pox, or in consequence of irritation of foreign bodies. It is not 
unusual to find small or even large ulcers in the mucosa of esophageal 
diverticula. These are occasioned by the retention of food. Peptic 
ulcers similar to those occurring in the stomach are occasionally found 
in the lower end of the esophagus. 

Phlegmonous esophagitis is rare. It may result from the extension 
of intense inflammation of the mucous membrane into the submucous 
tissue, or to penetration of the mucosa by sharp points of fish-bones and 
the like. 

The inflammation arising after swallowing corrosive or irritant 
substances may partake of all the above forms. It is usually, with 
milder substances, a desquamative process, but these may penetrate and 
produce a pseudomembranous condition due to destruction and separa- 
tion of the mucosa. With the more corrosive agents a rapid necrosis of 
mucosa or even submucosa may occur, with later development of hemor- 
rhages or dry ulcers. Suppuration, diffuse or localized, may occur. 
Connective-tissue overgrowth leads to alterations in the lumen. After 
severe damage the whole thickness of the mucosa may not be restored, 
there being merely a coating of epithelium for the scar tissue. 

There are sometimes encountered at autopsy pale firm areas over the 
esophageal mucosa which on microscopic study are found to consist of 
hyperkeratinization of the epithelium; this is called leukoplakia and is 
akin to this process in the buccal mucosa. It is said to arise from fre- 
quent exposure to irritating substances and to favor cancerous growth. 
It, however, does not resemble inflammation nor epithelioma. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



639 



STENOSIS 

Stenosis of the esophagus may be due to the pressure of tumors 
or aneurysms upon the esophagus, to the lodgment of foreign bodies, 
to the growth of tumors in the esophageal walls, or to stricture of the 
esophagus. The last most frequently results from the healing of ulcera- 
tions caused by the swallowing of corrosive liquids. Syphilitic and 
posttyphoidal strictures are rare. Carcinoma of the esophagus may 
obstruct by the growth within or by the attendant contraction of the 
walls. Occasionally stenosis by malformation is congenital. 

., Acute stenosis is a muscular spasm of the walls due to irritation, or 
as a part of hysteria or general convulsions. 

DILATATION 

Dilatation of the esophagus may occur in the form of a simple 
dilatation or ectasia, or in the form of diverticula. The former variety 
is common at the lower end of the esophagus, and is occasioned by ob- 
structions at ' the cardiac end of the stomach, or at the point where the 
esophagus passes through the diaphragm. The dilatation may reach 
considerable size. The mucous membrane 
and wall hypertrophy at first, the former even 
showing polypoid growths, but atrophy or 
ulceration appear later. 

An " idiopathic form" has been described, 
in which there is more or less uniform or 
spindle-shaped widening, probably due to 
atony of the musculature or to vagus disease; 
in these cases the musculature is atrophic, the 
mucosa, flat, dry or ulcerated. Spasmodic 
contraction of the cardia is also described as 
a cause. 

Diverticula may be of two kinds, those 
due to pressure from within (pulsion divertic- 
ula) and those due to traction from without 
(traction diverticula) (Fig. 285). The former 
are more commonly found in the upper portion 
of the esophagus or the lower part of the 
pharynx, and arise from the posterior wall of 
the esophagus. They are due to thinning of the 

muscular coat and to hernia-like protrusion of the mucous membrane. 
Food enters and, by its accumulation with fermentation, distention 
continues; any muscle that may remain is thus weakened. These sacs 
usually extend down between the esophagus and the vertebrae. The 
traction diverticula are most frequently found near the lower end, oppo- 
site the bifurcation of the trachea. They are caused by adhesion of 
diseased bronchial glands and subsequent contraction of the attach- 
ments. They occupy the anterior wall of the esophagus and have a 
somewhat funnel shape. Perforation may occur, with the development 
of septic infection of the pleura, pericardium, or lungs. Perforation of 
the pulmonary arteries may lead to fatal hemorrhage. 




Fig. 285. — Traction divertic- 
ulum of the esophagus (modi- 
fied from Birch-Hirschf eld) . 



640 



A TEXT-BOOK OF PATHOLOGY 



PERFORATION AND RUPTURE 

The esophagus may be perforated by necrotic or suppurative proc- 
esses surrounding it, or as the result of ulcers proceeding from within. 
Aneurysms of the thoracic aorta occasionally rupture into the esophagus. 
Retropharyngeal abscesses and phlegmonous inflammations of the 
deep cervical tissues may likewise discharge into the esophagus. Per- 
foration by ulcers beginning within may be due to the lodgment of 
foreign bodies, or to the pressure of the cricoid cartilage in cases of 
great asthenia (see Pharynx) . Perforation of the 
lower end of the esophagus may result from 
peptic ulcers or esophagomalacia due to re- 
gurgitation of gastric liquid either before or 
after death. Spontaneous rupture of the 
esophagus during swallowing or vomiting occa- 
sionally takes place. In these cases there is 
doubtless always some antecedent weakness of 
the svalls. 

INFECTIOUS DISEASES 

Tuberculosis of the esophagus is extremely 
rare, and most frequently results from extension 
of tuberculous adenitis of the bronchial glands. 

Syphilis occasionally occurs in the form of 
ulceration and cicatrization, leading to stenosis. 

Typhoid ulceration is probably more fre- 
quent than has been generally thought. Oc- 
casionally stenosis is caused by the cicatrices 
of the healed ulcers. 

Thrush may extend from the mucous mem- 
brane of the mouth and pharynx. 

Foreign bodies, like small bones, have been 
found embedded in the esophageal wall. 

TUMORS 

Fibroma, myoma, lipoma, or even sarcoma 
may occur as somewhat polypoid submucous 
tumors, but are rare. Papillomata, in the form 
of outgrowths of the mucous membrane, are 
more common. 

The most important tumor is carcinoma, 
which is usually found in the lower part, generally 
at the position where the left bronchus crosses the esophagus, or near 
the passage of the tube through the diaphragm. 

It may, however., be found at any part. The squamous variety is 
the most common, through a few instances of glandular carcinoma are 
recorded. The tumor usually involves the entire lumen of the esophagus 
projecting inward and forming irregular elevations of the mucous mem- 
brane. Later, the growth extends outward through the muscular coat 
to the fibrous outer layer, and even to the surrounding tissues. Dilata- 
tion occurs above the tumor, and occasionally perforation results from 




Fig. 286. — Carcinoma of 
upper end of esophagus 
(from a specimen in the 
collection of Dp. A. J. 
Smith). 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



641 



ulcerations caused by retained food. Extension occurs very frequently 
to the mediastinum and metastasis to the supra and infraclavicular glands, 
usually on the right side first. 

Cysts of the esophagus may occur. They are supposed to be due to 
misplaced lung or tracheal tissue. Many of them contain ciliated epi- 
thelial lining, strongly suggesting the latter origin. 

The Stomach 
congenital defects 

Complete absence of the stomach has been found in certain mon- 
strosities; but stenosis or atresia of the pylorus, division by the forma- 
tion of septa, and hour-glass contractions have been more frequently 
observed. In cases of transposition of the viscera the stomach may be 
reversed in its position, the pylorus being on the left side, the cardiac 
end to the right. 

Congenital hypertrophic stenosis of the pylorus with or without 
dilatation of the stomach has been found more common than previously 
thought. The hypertrophy may affect either the pyloric mucosa or 
muscularis, or both. This is entirely apart from spastic stenosis of the 
pylorus in children, which has no anatomical basis. There may be some 
inflammation with the pyloric stenosis. 

There is occasionally a hypertrophy of the middle of the stomach 
wall which gives a picture somewhat like hour-glass stomach, and, of 
course, this condition can be simulated in later life, by cicatricial con- 
traction. During digestion the midpiece of the organ contracts so far 
that there is a similarity to congenital hour-glass deformity. 

CIRCULATORY DISTURBANCES 
Anemia of the mucous membrane is found in cases of general ane- 
mia, particularly in pernicious anemia. The mucosa has an extremely 
pallid appearance and is prone to undergo fatty degeneration and 
atrophy. 

• Hyperemia. — Active congestion occurs in the beginning stages of in- 
flammation of the mucous membrane of the stomach, and results from 
irritating mechanical or chemical agents. The mucosa is bright red in 
color and may present minute hemorrhages. Moderate hyperemia is 
functional during the period of digestion. 

Passive hyperemia occurs as a result of obstructive heart disease or, 
more particularly, from obstruction of the portal circulation by cirrhosis 
or other diseases of the liver. Pulmonary affections, by interfering with 
the outflow of blood from the right side of the heart, may also occasion 
congestion of the stomach. The mucosa is dark red in color, swollen, 
and often edematous. Minute hemorrhages may occur, and small 
erosions may appear upon the surface. The changes are more marked 
near the pyloric end of the stomach. When the congestion has per- 
sisted for some time, dark reddish or bluish pigmentation, usually occur- 
ring in punctate form, is developed and chronic gastritis results. 

Hemorrhage in the mucous membrane or from the mucous mem- 
brane of the stomach results from a variety of causes. Small petechiae 
are met with in active or passive congestion and in acute inflammations, 

41 



642 



A TEXT-BOOK OF PATHOLOGY 



and they may follow thrombosis or embolism of the gastric vessels. 
Milder poisons cause them. They are also present in various infectious 
or hemorrhagic diseases, such as purpura, scurvy, septicemia and the 
like, and in anemic affections like pernicious anemia. In many cases 
punctiform hemorrhages are developed just before death. 

These are all submucous hemorrhages, from the overlying mucosa 
of which the gastric juice may digest the covering, leaving erosions which 
may go on into distinct ulcerations. 

Larger hemorrhages, and particularly hemorrhages into the cavity 
of the stomach, result from intense passive congestion in cardiac dis- 
ease or cirrhosis of the liver, and from gastric ulceration or carcinoma. 
When large vessels have not been eroded the blood escapes gradually, 
and may be vomited in a semidigested and disorganized condition (coffee- 
ground vomit). This is peculiarly significant of carcinoma. When 
one of the larger vessels has been eroded, large quantities of fresh blood 
may be vomited and rapid death may occur. Occasionally hemor- 
rhage from the stomach in considerable quantity occurs in cases in which 
there is no visible lesion of the mucosa. 

Melcena neonatorum, the vomiting of blood by the newborn, results 
from gastric hemorrhage due to disturbances of circulation because of 
insufficient respiration, and possibly in other cases is a vaiiety of infec- 
tious hemorrhagic disease. 

INFLAMMATION 

Acute inflammation of the mucosa, or acute gastritis, results 
from irritation by chemical, mechanical, or thermal agents. Some cases 
are doubtless due to infection. The mucous membrane is bright red 
and covered with more or less viscid mucous exudate. Punctate hemor- 
rhages may occur. Microscopically, there are found: marked mucous 
degeneration of the cylindrical cells of the tubules, and desquamation 
and granular degeneration of the cuboidal cells in the fundus of the 
glands. The mucous membrane between the tubules is infiltrated with 
round cells, and not rarely the same process occurs in the submucosa. 
The collections of lymphatic tissue (follicles) in the mucous membrane 
are often hyperplastic. Acute gastritis is more frequently found near 
the pyloric end than elsewhere. During puerperal sepsis, acute endo- 
carditis or in association with ulcer or cancer, exudative phlegmonous 
inflammations may make their appearance, usually involving the sub- 
mucosa over which the mucosa soon sloughs off. Perforation of such 
lesions, causing peritonitis, is the usual result. 

Lesions, the result of the swallowing of poisons, are really not forms of 
gastritis but rather in the nature of solutions of the wall, or eschars. 
The appearances depend upon many circumstances, notably the amount 
of poison consumed, its concentration and the material in the stomach 
when the irritant reaches it. Substances like phenol, corrosive sub- 
limate, and strong acids produce black, gray or white eschars beneath 
which hemorrhage may occur or at least an area of intense congestion 
arises. Alkalies make the mucosa soft, swollen, pale, digested and loos- 
ened, while the submucosa may be little altered. These facts are for 
acutely poisonous quantities while if the amounts be small a pseudo- 



DISEASES OF THE GASTROINTESTINAL TRACT 



643 



membranous inflammation may arise. When the immediate result is not 
fatal the gastric mucosa heals by scar tissue without glands or, in the 
milder poisonings, by one of the forms of chronic gastritis. 

In considering the role of bacteria in the causation of gastritis it 
must be remembered that the bacteria normal to the stomach are few 
and not pathogenic. Most pathogenic bacteria are destroyed in the 
normal stomach. When, however, gastric mucosa and juice are altered 
by irritant poisons or by the fermentations and putrefactions arising 
in food taken to excess, especially in the presence of deficient propelling 
power by the muscular coat, the natural protective powers of the stom- 
ach are reduced. In such cases pathogenic germs introduced with the 
food thrive and attack the damaged walls. The normal flora comprises 
sarcinse, moulds, and yeasts. 

Pseudomembranous gastritis may result from the ingestion of cor- 
rosive poisons, and is occasionally seen in small-pox, typhus fever, and 
various forms of septicemia. It may be met with in diphtheria, and 
may be due to direct extension of the process along the esophagus. 
The surface of the mucosa is covered with an irregular membrane, and 
necrosis and ulceration are not rarely observed, especially in cases due 
to corrosive poisons. 

Ulcerative Gastritis. — Small erosions may be found in cases of ex- 
treme congestion or petechial hemorrhage, as well as in acute gastritis. 
Actual ulceration is seen in pseudomembranous gastritis, and occa- 
sionally as a result of septic embolism in the mucosa in cases of malignant 
endocarditis. Infectious ulcerations occur in gastro-intestinal tubercu- 
losis, anthrax, and in typhoid fever, but are very rare. 

Chronic gastritis may result from repeated attacks of acute gas- 
tritis, and is especially prone to occur from improper habits of eating 
or from the abuse of alcohol. Chronic congestion, such as occurs in 
heart disease, strongly predisposes. 

Pathological Anatomy. — -The appearance of the mucous membrane 
vaiies greatly. In the milder cases the surface is more or less irregular 
and granular, and is covered with mucous exudate. The color may be 
grayish, but in cases in which passive congestion has preceded the de- 
velopment of gastritis it is often slate colored from pigmentation. 

Microscopically, there may be found mucous degeneration of the 
cylindrical epithelium of the tubules, and desquamation and not rarely 
proliferation of the secretory epithelium in the fundus of the glands. 
The glands may be considerably dilated and filled with mucous exudate 
and desquamated cells. The interglandular tissues are infiltrated, 
and may be thickened by the formation of new connective tissue; the 
same process may involve the submucous coat. The blood-vessels of 
the latter are often greatly dilated and their walls may be thickened. 
In the later stages the glands may undergo progressive atrophy, the epi- 
thelium disappearing almost entirely and the lumen of the gland be- 
coming less and less distinct. Coincidently with these changes, and to 
some extent causing them, there is fibrous overgrowth of the interglandu- 
lar tissues. 

In some instances the contraction of the new-formed connective 
tissue causes protrusions of the mucous membrane or polypoid eleva- 



644 



A TEXT-BOOK OF PATHOLOGY 



tions (Fig. 287). These may still further enlarge by proliferation and 
cystic distention of their glandular elements. In other cases the pro- 
liferative changes in the interglandular tissues may be more diffuse and 




Fig. 287. — Polyposis of stomach (from the Vienna General Hospital collection). 

the mucous membrane more regularly thickened (Fig. 288). To both of 
these forms the name hypertrophic gastritis may be applied. In still 
other cases the formation of fibrous tissue causes pressure-atrophy of 




Fig. 288. — Chronic catarrh of the stomach with thickening of the mucosa (from the Vienna 

General Hospital Collection). 

the glands; the surface in these cases becomes smooth and the mucosa 
greatly thinned (atrophic gastritis). 

The sclerotic process may involve not only the mucous membrane, 
but also the submucous and even the muscular coat. In such cases the 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



645 



thickness of the walls of the stomach may increase greatly, and the size 
of the organ greatly diminish by contraction. The terms interstitial 
gastritis, linitis gastrica, and leather-bottle stomach have been applied to 
such cases. It is sometimes difficult to distinguish such cases from 
diffuse scirrhous carcinoma. • 

Pathological Physiology in Gastritis. — AH forms of gastritis cause 
disturbances of the functions of the stomach, designated by the terms 
dyspepsia and indigestion. These disturbances are due to abnormal 
secretion of the gastric glands, reduced motor power of the walls of the 
stomach, and altered conditions of the nervous mechanism. The most 
important alteration of secretion is reduction of the amount of hydro- 
chloric acid. This is almost constant in uncomplicated gastritis; in some 
cases there is practically no hydrochloric acid reaction. The ferments^ 
pepsin and curdling ferment, may be produced in insufficient amount, 
but are very rarely absent. In cases in which certain general conditions 
or nervous affections coexist with moderate gastritis, excess of hydro- 
chloric acid secretion occurs. Reduction in the amount of hydrochloric 
acid causes delay and inadequacy of digestion of proteins. When the 
acid is wholly wanting, decomposition of the proteins may occur, and 
sulphuretted hydrogen and other products of decomposition result. 
Excess of hydrochloric acid interferes with salivary digestion in the 
stomach, and, in consequence, fermentation of carbohydrates, with pro- 
duction of lactic, butyric, or acetic acid and of various gases, takes place 
Such fermentation, however, is not, as a rule, observed unless the motor 
power of the stomach is deficient and the food is retained in the stomach 
beyond the usual time. It is not improbable that toxic substances are 
produced in some cases by protein decomposition, but accurate ob- 
servations are wanting. 

The motor power is usually deficient in proportion to the intensity 
of the gastric disease. In some cases the food is retained many hours 
longer than the usual periods, and fermentation and decomposition are 
thus greatly favored. Dilatation of the stomach may be brought about 
by the retention of food and the accumulation of gases of decomposition, 
and the dilatation, in turn, increases the motor insufficiency of the 
wall. 

Altered conditions of the nervous mechanism of the stomach mani- 
fest themselves in a variety of ways. Sometimes there is excessive 
irritability of the mucosa, causing vomiting; in other cases a feeling of 
heaviness or pain. Alterations of appetite and of gastric motility are 
other results probably brought about, in part at least, through nervous 
disturbances. It has been thought that gastric hyperactivity, both 
muscular and secretory, are the results of vagus irritation while atonic 
states owe their origin to disturbances of the sympathetic system. 
For these so-called "gastric neuroses'' there is, however, no essential 
pathology. 

The general metabolism suffers profoundly in gastric disease — 
mainly in consequence of the insufficient food eaten or digested. Ema- 
ciation and systemic depression are the clinical consequences. It is 
possible that toxic substances produced in the stomach contribute to 
the metabolic disturbances, but this remains to be proved. 



646 



A TEXT-BOOK OF PATHOLOGY 



GASTRIC ULCER 

Gastric, peptic, or round ulcers are roughly circular defects of the 
mucosa and part of the submucosa, probably due to the digestive action 
of the gastric juice upon a section of stomach wall previously deprived 
of its natural resistance. Similar lesions may occur in the upper end of 
the duodenum and in the lower end of the esophagus. Mayo has 
insisted that duodenal ulcers are much more frequent than has been 
heretofore believed, and that they are more common in men than in 
women. 

Etiology. — Many cases occur in young women suffering from chlorosis 
or anemia and general malnutrition, but the majority of peptic ulcers 
occur in males. The pathogenesis of these ulcers has occasioned 
much dispute. It is admitted that they are due to the action of the 
gastric juice upon parts of lowered vitality, and the term ulcus ex- 
digestone is, therefore, appropriate. Increased acidity of the gastric 
juice is an undoubted factor. The lowered vitality which localizes 
the ulceration has been ascribed to many causes. Embolism or throm- 
bosis with infarction was suggested by the shape of the ulcers, and may 
be the explanation for some cases. Spasm of the blood-vessels in 
localized areas, possibly due to stimulation of the vagus, and thickening 
of the walls of the vessels, leading to anemia, have been suggested, as 
have also direct traumatic injuiies of the mucous membrane and ex- 
ternal traumatism, causing rents of the mucous surface. Circulatory 
disturbances due to tight lacing are supposed by some to be important. 
When these peptic ulcers occur beyond the pylorus in the duodenum, 
they very rarely appear below where the intestinal contents are acid. 

For the chronic ulcers, alterations in the position and rugosity of 
the mucosa probably play a part. If the mucosa be thrown or drawn 
mechanically into abnormal folds the circulation is naturally altered 
and resistance to autodigestion decreased. Adhesions without may also 
have such a result. By some authors blood-vessel changes are held 
responsible, as arteriosclerosis, endo-arteritis, and thrombosis are 
exceedingly common in the vessels supplying the affected parts. It is 
probably well at this time, when the question is as yet unsettled, to 
explain peptic ulcers as the result of the action of gastric juice, probably 
high in acidity, upon a small locality deprived of its resistance. The 
multiple benign ulcers seen in general infections or blood dyscrasias are 
doubtless of the same origin. They seldom if ever perforate, and give 
no symptoms. 

Gastric ulcers have been attributed to streptococcal embolism and 
thrombosis. Superficial ulcerations are said to occur if bile enters the 
stomach when there is 0.5 per cent, or more of hydrochloric acid present. 
Both of the above statements gain somewhat in value in view of the ex- 
perimental observations that streptococci are resistant to the antibac- 
terial action of the bile. Trypsin from the duodenal contents, entering 
an atonic stomach by reason of a relaxed pylorus, is said to have a potent 
effect on ulcer production. These observations by American workers 
may assist in clearing up the etiology of peptic ulcers. 

Pathological Anatomy. — Peptic ulcers are usually single, but may be 
multiple. They are commonly situated in the lesser curvature and the 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



647 




Fig. 291. — Stellate scar of a healed ulcer of the stomach (Bollinger). 



648 



A TEXT-BOOK OF PATHOLOGY 



posterior wall of the stomach, near the pylorus; occasionally they are 
found at the fundus or at the cardiac end. A striking form is the large 
saddle-shaped ulcer which has a narrow part in the lesser curvature 
and large spreading wings in the anterior and posterior wall of the 
stomach. They vary in diameter from a few millimeters to 3 or 5 
cm. Their shape is characteristic in that they have sloping edges, giving 
them a funnel form, with the apex toward the muscular coat. The 
shape corresponds to the distribution of the gastric arterioles. The edges 
may be irregular and rough, but are often, especially in older ulcers, quite 
smooth and rounded. The duodenum is sometimes the seat of ulcers 
of the same type, especially in the stretch above the papilla where the 
the mucosa is exposed to the gastric juice before it is neutralized; they 
are usually small, round, ragged but sluggish. 

Two dangers are always imminent — hemorrhage and perforation. 
Constant oozing of blood may be due to erosion of the surface, and 
larger hemorrhages may result from ulceration of one of the larger 
arterial branches of the stomach (Fig. 289). Perforation is less common 
than hemorrhage. When the ulcer is situated posteriorly perforation 
is prevented by adhesions attaching the stomach to the head of the 
pancreas or other structures. When the ulcer is in the anterior wall per- 
foration is more liable to take place (Fig. 290). The rupture may occur 
into the peritoneal cavity or into any of the surrounding structures, and 
fistulous communications may be established with the pleural or peri- 
cardial cavities, or even with the exterior through the abdominal walls. 
Abscesses of the liver, spleen, or pancreas may res lit from perforation 
into these organs. 

Microscopically, there is little to be seen aside from loss of surface 
tissue. In the older cases a slight circumferential fibrous tissue in- 
crease, especially at the thickened margin, may be found. 

In the healing of the ulcers scars are formed in the wall of the stom- 
ach. These have usually a rather characteristic stellate shape (Fig. 291). 
In case of large ulcers extensive scars and considerable contraction of 
portions of the walls of the stomach result. Hour-glass contraction of 
the organ, or pyloric stenosis, may follow, and secondary changes, such 
as gastric dilatation, may ensue. Carcinomatous transformation is a 
not infrequent result of long-standing ulceration. 

ATROPHY AND DEGENERATIONS 

Atrophy of the glands or gastric tubules is frequently seen in chronic 
gastritis. The same condition occurs as a senile change and in asso- 
ciation with various chronic diseases, especially pernicious anemia. A 
certain amount of atrophy of the entire mucous membrane results in a 
purely mechanical way from gastric dilatation. 

Decrease in the size of the stomach as a whole may be the result 
of chronic gastritis, when the new-formed connective tissue contracts. 
In such cases the stomach may become quite small, the walls, however, 
increasing in thickness. Somewhat similar shrinkage in the size of the 
stomach occurs in some instances of infiltrating cancer of the stomach. 
The tumor may involve all parts of the organ equally, and cause more 



DISEASES OF THE GASTROINTESTINAL TRACT 



649 



or less thickening of its walls, but the size of the organ is diminished by 
contraction of the connective tissues. 

A form of true atrophy is sometimes caused by obstruction of the 
cardiac orifice; it is probably due, in part at least, to the insufficiency of 
food admitted to the stomach. 




Fig. 292.- — Atrophy of the gastric mucosa in pernicious anemia. 



Degenerations of the mucous membrane of the stomach are met 
with either in association with inflammation or as independent affec- 
tions. 

Fatty degeneration of the epithelial cells of the glands may be the 
result of intoxications (phosphorus, arsenic), or of conditions such as 
those which lead to simple atrophy. The occurrence of atrophy and fatty 
degeneration of the gastric tubules in cases of pernicious anemia is of 
great importance, though it remains unsettled whether these conditions 
are the cause or result of the anemia. 

Pigmentation is met with as a result of chronic congestion or hemor- 
rhage into the mucous membrane. The mucosa has a dark red or often 
a slaty discoloration, which is prone to be distributed in lines or in cir- 
cumscribed patches. Bluish pigmentation of the stomach sometimes 
occurs from the ingestion of silver. 

Amyloid infiltration may be found around the blood-vessels of the 
submucosa, or more rarely of the mucosa itself, in cases of general amy- 
loid disease. Amyloid ulcerations may occur. 

Calcification has been met with in cases of bone disease with sur- 
charge of the blood with earthy salts. It appears between the glands of 
the fundus lying near the surface of the mucosa. 



650 



A TEXT-BOOK OF PATHOLOGY 



Gastromalacia, or simple softening of the walls of the stomach, is 
usually a postmortem condition, and is due to the action of the gastric 
juice. The nature of this process has occasioned much discussion, but it 
is now recognized as a postmortem condition, or as a condition occurring 
during life only in the agonal period. It affects the fundus or posterior 
part of the stomach. The mucous membrane becomes soft and more 
or less gelatinous, and is grayish or yellowish in color if the mucosa was 
anemic, or brownish in cases in which there was congestion before 
death. Rupture and discharge of the contents of the stomach into the 
peritoneal cavity, spleen, or other adjacent organs may occur. The 
walls of the stomach in the affected area show granular degeneration of 
the component cells, but no evidences of inflammatory reaction, and 
when rupture has occurred there are no reactive inflammatory lesions 
of the peritoneum, showing that the perforation occurred after death. 

ALTERATIONS IN POSITION AND SIZE 

Alterations in Position. — The stomach may be displaced into the 
thoracic cavity in cases of perforation or rupture of the diaphragm 
(diaphragmatic hernia). It may be displaced anteriorly as a congenital 
malposition in consequence of defects of the anterior abdominal walls, 
and may in such cases be quite exposed. Downward dislocation, or 
gastroptosis, is either congenital or acquired. The acquired form may be 
due to diseases of the stomach, particularly dilatation, to the traction of 
inflammatory adhesions, to enlargement of the spleen, and probably to 
tight lacing. Occasionally in anemic and relaxed women all of the ab- 
dominal viscera tend to descend (splanchnoptosis). 

Dilatation, or gastrectasia, most frequently results from obstruction 
of the pylorus. The latter may be due to cicatrization the result of the 
healing of ulcers, to fibroid overgrowth and contraction the result of 
chronic gastritis, or to pyloric carcinoma. The pressure of tumors, of a 
movable kidney, or of aneurysms may act similarly. At first, pyloric 
stenosis may be compensated by hypertrophy of the muscular layer of 
the stomach, but soon dilatation occurs; food stagnates, fermentation 
takes place, and the dilatation is increased. The mucosa becomes thin 
and ofttimes degenerated and atrophic, the exact changes being those 
of the specific variety of gastritis existing. 

A second group of cases (atonic dilatation) is independent of stenosis 
of the pylorus, but due to weakness of the walls of the stomach. The 
latter may be the result of chronic gastritis or of a general atonic state. 
Constant overeating may play an important part in some cases. Finally, 
dilatation may result mechanically from abnormal adhesions of the 
stomach. 

Dilatation of the stomach occasions great stagnation of food and, 
in . consequence, imperfect digestion and decomposition of the food. 
When hydrochloric acid is absent (as in cancerous stenosis of the pylorus 
and marked atonic dilatation) lactic acid fermentation is pronounced; 
when hydrochloric acid is present lactic acid is less abundant or absent. 
Sulphuretted hydrogen and inflammable gases are occasionally formed, 
especially in cases in which hydrochloric acid is present. The mucous 
membrane of dilated stomachs loses its absorptive power to a large de- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



651 



gree. This, together with the retention of ingested liquid in the stom- 
ach and the consequent lessening of intestinal absorption, leads to great 
emaciation, and especially to desiccation of the tissues. The muscu- 
laris shows hyaline change and thinning, with elongation of the fibers. 
The mucosa shows atrophic glands, with fatty cells. 

Among the micro-organisms met with in the gastric contents the 
Sarcince ventriculi are of interest. These occur in bundles of peculiar 
square form. The sarcina is more frequent in non-cancerous than in 
cancerous dilatation. In cases of dilatation due to cancer of the stom- 
ach the Oppler-Boas bacillus is found (see below). 

An acute form of gastric dilatation sometimes occurs after anes- 
thesia, following indiscretions in diet, as a result of pressure on the duo- 
denum when the mesentery is pulled upon by twists of the intestine, 
after traumatism, and at times without demonstrable cause. The most 
frequent anatomical factor is twisting of the intestinal loops, especially 
in the presence of an abnormally long mesentery. The method of action 
of these causes is not clear, but they probably operate by paralyzing the 
gastric wall. 

INFECTIOUS DISEASES 

A few cases of tuberculous ulceration have been recorded, and syph- 
ilitic gummata or ulceration may occur. The tuberculous processes may 
be hematogenic or localized, in which latter case they are secondary to 
peptic ulcer; they assume a ragged, punched-out appearance and seldom 
perforate. Diffuse cirrhosis and ordinary gastritis may be dependent 
upon syphilis, but the etiological connection is uncertain. Anthrax may 
lead to necrotic and hemorrhagic ulcers of the mucosa. Thrush is rarely 
met with, though the spores of the sactmaromyces are frequently present 
in the stomach when the mouth is affected. 

TUMORS 

Connective=tissue Tumors. — Fibroma, myoma, and lipoma are 
occasionally met with as submucous or subserous polypoidal tumors. 
Sarcoma is rare. It affects the lymphoid tissues of the deeper parts of 
the mucosa, and rapidly spreads to the submucosa. Most cases are 
of the round-cell variety. Lymphoid infiltrates of the adenoid tissues of 
the stomach may be one of the lesions of leukemia or Hodgkin's 
disease. 

Epithelial Tumors. — Polypoid elevations, sometimes with cystic en- 
largement of the glands, occur as a result of chronic inflammation, and 
may be large enough to be regarded as tumors in a clinical sense. Adeno- 
matous proliferation of the glands is met with in the form of irregular, 
flat tumors, or as large pedunculated masses hanging free in the cavity. 
True adenoma of tubular and acinar arrangement are rarely seen as 
diffuse or nodular thickenings of the gastric wall. 

Carcinoma is the most frequent tumor of the stomach. It occurs at 
middle age, and more often in the male sex than in the female. The 
pyloric end of the organ and the lesser curvature are the favorite sites, 
but other parts may be affected and the entire organ may be involved. 
Cancer of the stomach may appear as a ring-like swelling of the mucous 



652 



A TEXT-BOOK OF PATHOLOGY 




DISEASES OF THE GASTROINTESTINAL TRACT 



653 



membrane and submucous tissue, surrounding the pylorus and causing 
stenosis; as more or less circular, flat elevations in the lesser curvature 
or elsewhere; and, finally, as a diffuse infiltration of the mucosa, sub- 
mucosa, or all of the coats of the entire organ. The mucous surface is 
generally irregularis elevated, and tends to become ulcerated, especially 
in medullary cancer and in the cases in which there are localized flat 
elevations. Sometimes portions of the cancerous tissue may be found in 
the vomitus, and the diagnosis of the disease may be thus established (Fig. 
293) . Perforation of the wall of the stomach may result from necrotic and 
ulcerative processes (Fig. 295). The neighboring lymphatic glands, 
especially those in the lesser curvature of the stomach, are usually impli- 
cated through the lymphatic vessels. Direct extension to the peritoneum 
may occur, especially in cases of colloid cancer; and metastasis through 
the blood-ves sels is extremely common. Cancerous emboli are frequently 
found in the portal radicles within the liver, and multiple cancer-nodes 
of the liver are usually found in cases which have existed for some length 
of time. Hematogenous metastasis is most common in soft, ulcerating 
cancers. 



Fig. 295. — Carcinoma of the cardiac end of the stomach; extension into duodenum: 
S, Dilated esophagus; K, ulcerated carcinoma; G, a perforating ulceration; M, stomach 
(Orth). 

Varieties. —There may be distinguished hard or scirrhous cancers, 
soft or medullary cancers, adenocarcinomata or malignant adenomata, and 
cylindrical-celled or squamous-celled carcinomata. All forms begin in 
the mucous membrane and spread to the submucosa. The muscu- 
laris may be penetrated and infiltration of the serosa, or even of sur- 
rounding tissues, may be observed. 

Scirrhous cancer may appear as a circular constricting new growth 
at the pylorus (Fig. 296). In other cases the disease is extensive, and 
the entire organ may be involved by uniform infiltration, and macro- 
scopically the appearance of a simple cirrhosis of the stomach is pre- 
sented. In the last-mentioned variety the organ may be greatly reduced 
in size, though the walls are greatly thickened, the whole wall having the 
thickness as shown around the pylorus in Fig. 296. The mucous surface 
rarely ulcerates in scirrhus. 




654 



A TEXT-BOOK OF PATHOLOGY 



Medullary or soft cancer usually appears as a localized tumor at the 
pylorus or in the lesser curvature. The mucous membrane is irregularly 
elevated, ofttimes in a cauliflower manner (Fig. 297). Ulceration on 
the surface is common, and hemorrhagic extravasation into the stomach 
is, therefore, frequent. Metastasis through the blood is liable to occur. 
Complete perforation of the stomach may take place. 




Fig. 296. — Scirrhus of the pylorus, causing pyloric stenosis: D, Duodenum; P, pylorus; 
K, carcinomatous projections on the mucosa (Orth). 

Malignant adenoma, or adenocarcinoma, begins as a proliferation 
of gastric tubules. The new-formed acini are, however, atypical in ar- 
rangement and number, and there is a tendency to conversion of the 
normal cylindrical cells into cuboidal cells, and to extensive cancerous 
infiltration by excessive formation of acini or tubules, as well as by de- 



M 




Fig. 297. — Cauliflower carcinoma of pylorus: M, Stomach; P, pylorus; D, duodenum 

(Orth). 

struction of the basement-membrane of the acini and irregular cellular 
invasion. The appearance of the tumor and its tendencies are the same 
as those of soft cancer. 

Cylindrical cancer, or cylindrical epithelioma, probably arises from 
the cylindrical lining cells of the stomach, or from the cells in the upper 
parts of the tubules. Atypical tubular aggregations of cylindrical cells 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



655 



with a tendency to conversion into cuboidal cells are observed. The 
pylorus is the common seat. 

Squamous cancer occurs at the cardiac end, and generally in asso- 
ciation with carcinoma of the lower end of the esophagus, from which 
the squamous epithelium extends a short distance into the stomach. 
It is rare. 

Colloid cancer of the stomach appears as a localized or, more fre- 
quently, diffuse infiltrating, gelatinous new growth of the mucosa and 
submucosa. Rapid extension through the walls of the stomach and to 
the peritoneum is frequent. The cells and the stroma of the tumor show 
myxomatous degeneration, and the epithelial elements may in the later 
stages entirely disappear. Extensive invasion of the peritoneum is not 
infrequent. 




Fig. 298. — A cross-section of gastric ulcer showing the beginning of a carcinoma. 
The pale area is the cancer infiltrating the submucosa. 

Pathological Physiology and Results. — Carcinoma of the stomach 
is most frequently situated at or near the pylorus, and, therefore, inter- 
feres with the propulsion of food, both by mechanical opposition and by 
stiffening of the wall, as it involves the submucosa and muscularis. 
Stagnation of the stomach contents and fermentation result. The latter 
is favored by the absence of hydrochloric acid secretion so habitually 
observed. In consequence of the stagnation the stomach dilates and may 
reach enormous size, not rarely filling a large part of the abdominal cavity. 
Lactic acid fermentation is frequently pronounced. Disturbances of 
metabolism, with loss of flesh and strength, are marked. Among the 
micro-organisms present in the stomach contents a long, thread-like 
bacillus (Oppler-Boas) has attracted much attention, and has been sup- 
posed by some to occur only in cancer of the stomach. It is certainly 
frequent, but just as certainly not peculiar to the disease. 

The Intestines 
congenital and acquired abnormalities 

Occasionally total absence of large parts of the intestinal tract is found 
in monstrosities. Lesser defects, leading to narrowing or distortion of 
the intestines, are more frequent. Marked developmental defects most 
frequently occur in the rectum, which may be completely absent, or may 



656 



A TEXT-BOOK OF PATHOLOGY 



be obliterated at the lower end. In such cases there may be fistulous 
communications with the urogenital tract, or there may be a persistent 
cloaca, as in fetal life. 

Congenital Enlargement of the Intestines. — The colon is most 
apt to be affected, and may be greatly enlarged, the most important ex- 
ample of which is Hirschsprung's disease or megacolon. The ascending 
and transverse portions of the large gut are usually greatly dilated and 
have very much thickened walls while the sigmoid is commonly longer 
than normal, has thickened walls but may not be distended in caliber. 
By some, atony or incompletion of the musculature is held responsible, 
while others look upon it as obstructive from abnormalities in the 
mesocolon. 

Diverticula. — Localized dilatations, constituting • diverticula, are 
frequent, the most common form being Meckel's diverticulum. This 
usually arises from the ileum, about 1 meter above the ileocecal valve, 
and is attached to the intestine opposite the mesentery. It represents 
the remains of the omphalomesenteric duct of fetal life. Occasionally 
it has been found patulous to the umbilicus. More commonly there 
is merely a short diverticulum of the intestines, varying from a few to 
several centimeters in length, and having a closed extremity which may 
be somewhat dilated. The extremity may be connected with the umbilicus 
by a cord, but is usually free. 

The importance of the diverticula, especially the Meckel variety, 
is that they may be involved in inflammation which may lead to per- 
foration or to adhesions. In the latter case coils of intestines may be 
constricted and lead to ileus. Meckel's diverticulum, when not inflamed 
but if attached at the umbilicus, sometimes catches a knuckle of gut and 
leads to intestinal obstruction. 

Acquired diverticula occur at any age and appear at all parts of the 
intestinal tube. They are ascribed to faulty construction of the wall, to 
obstruction by stenosis or constipation, and to inflammatory weakening 
of the muscularis. In the small intestine they are most likely to be en- 
countered along the mesenteric insertion as more or less irregular swellings 
from the sac of which the musculature may be missing; a similar form 
has been seen affecting the appendix. In the colon, acquired diverticula 
are found most often bordering the longitudinal bands as numerous small 
swellings due to localized dilatations with thickened gut wall, or as larger 
thin-walled hernial protrusions containing rather inspissated feces. The 
former are believed to be due to inflammatory thickening and weakening 
of the wall while the latter are ascribed to hernise of the mucosa through 
the muscle, following clefts around blood-vessels, or where the muscle 
has degenerated for any reason. The sac in this case consists of mucosa 
and serosa. The result of these false diverticula, when numerous or 
large, is to weaken the wall and increase constipation, thus favoring 
production of others. Moreover there may arise thickenings and 
adhesions with adjacent organs. When the sigmoid is involved marked 
clinical symptoms arise, diverticulitis or pericolitis sinistra, demanding 
operation. 

Congenital Abnormalities in Position. — The position of the 
several parts of the intestinal tract may vary widely from the normal. 



DISEASES OF THE GASTROINTESTINAL TRACT 



657 



Not rarely the ascending colon and cecum are situated on the left side ; 
the sigmoid flexure and descending colon being on the right side. 

Cecum mobile is an abnormal looseness of cecum, sometimes leading 
to surgical conditions in this organ or the appendix. 

Enterocystoma. — A congenital cystic condition found at the um- 
bilicus has been described as cystic dilatation of parts of the original 
omphalomesenteric system of the fetus, and has been named " entero- 
cystoma." 

Dilatation. — More or less uniform enlargement of the intestines 
may result from long-standing constipation. Enormous dilatation of 
the colon is sometimes seen. In this the wall of the intestine undergoes 
compensatory hypertrophy, and small pouchings or diverticula are com- 
monly observed, especially in the rectum and sigmoid. 

This is the chronic dilatation. Acute dilatation is due to sudden 
obstruction, as from a foreign body or by paresis of the muscular wall, 
as occurs by blows on the abdomen. Again, the dilatation may be acute, 
but not necessarily sudden, when the gut walls are paralyzed by peri- 
tonitis or by toxins of diseases not localized to the abdomen (meningitis). 
Acute dilatation occurs in surgical shock. 

Narrowing, or stenosis, of the intestine at any part may be due 
to pressure of new growths or displaced viscera, to cicatricial constric- 
tions following ulcerations, or to neoplasms. Cicatricial stenosis is par- 
ticularly common in the rectum following dysenteric or syphilitic ulcers. 
Narrowing of the lumen may be due to an ingrowth of carcinoma or 
the presence of papillomatous or polypoid tumors within. The wall 
above the obstruction becomes hypertrophic while that below is collapsed 
and atonic. If the stenosis become greater so that collections increase 
above it, dilatation of the wall occurs or it may even rupture. 

Hernia. — This term is applied to malposition of any of the viscera, 
with displacement of the organ from the cavity in which it normally 
lies ; but it has been more particularly applied to such displacements of 
the intestines, and the single term "hernia" is significant of intestinal 
hernia. 

Occasionally hernise are present at birth but it is more common for 
them to appear at places where the closure of canals or apertures of the 
fetus has not been perfect and where protrusions occur after some severe 
muscular effort. The latter are called acquired hernice and are usually 
observed at the umbilicus and the femoral or inguinal canals. They 
should be distinguished, etiologically at least, from the artificially ac- 
quired variety which follows upon imperfectly closed wounds or weak 
scars from abdominal operations. In such cases where fibrous tissue 
replaces the abdominal muscle, there is greatly lessened ability to with- 
stand increased abdominal pressure so that even such ordinary exertions 
as defecation may cause hernia. 

Etiology. — The predisposition to hernia may consist in unnatural 
weakness of the abdominal wall, especially at the points where hernia 
is likely to occur, resulting from imperfect closure pf such portions or 
from general muscular weakness. Abnormal movability of the intestines, 
resulting from natural or acquired elongation of the mesenteric attach- 
ments and increased weight of the abdominal contents from the deposit 

42 



658 



A TEXT-BOOK OF PATHOLOGY 



of peritoneal fat, contributes largely to the formation of hernia?. The im- 
mediate exciting cause in many cases is strain, and probably in all cases 
repeated strain helps in the development of the protrusion. The most 
frequent form of ventral hernia is the umbilical, which occurs especially 
in infants as the result of imperfect closure of the abdominal walls at the 
umbilicus. 

There may be distinguished two groups or varieties — the internal and 
the external hernia?. 

Internal Hernia.— By this term are designated hernia-like displace- 
ments of the intestines into other cavities within the body, the most im- 
portant being upward displacement into the thorax through congenital 
or acquired clefts of the diaphragm (diaphragmatic hernia); and back- 
ward displacement through the peritoneum into the retroperitoneal space 
(retroperitoneal hernia). In this group belong also the passage of a 
knuckle of gut through holes in the mesentery, the most common seats 
for this probably being the duodeno-jejunal fossa and the ileocolic region. 
Such internal hernia? not infrequently become incarcerated and ob- 
structive. 

External hernia may be inguinal, femoral, ventral, vaginal, rectal, 
perineal, ischiatic, or obturator. The most frequent of these are the in- 
guinal and the femoral. In the former the protrusion may occur through 
the external inguinal ring, the intestine descending through the inguinal 
canal, sometimes as far as >the scrotum (indirect inguinal hernia). In 
another group of cases the intestine pushes directly forward through 
the abdominal wall and external inguinal ring, and may present anteriorly 
under the skin, or may descend through the lower part of the inguinal 
canal to the scrotum (direct inguinal hernia). The indirect inguinal 
hernia? are sometimes congenital, and are due to the failure of closure of 
the peritoneal reflection which passes downward through the inguinal 
canal. 

Femoral herniae are especially common in women, and are formed by 
protrusion of the intestine through the femoral ring, the hernia pre- 
senting on the inner side of the thigh, at the position of the saphenous 
opening. 

Pathological Anatomy . — The hernia consists of a sac or wall and of 
the contents of the hernia. The sac is usually constricted at its junction 
with the general peritoneal cavity (neck), and distended and dilated 
outside of or below this point (fundus or body of sac). The sac of the 
hernia is always lined with the protruded portion of the peritoneum. The 
contents of the hernia may be coils of intestine or portions of omentum, 
or both. Most frequently some part of the small intestine occupies the 
hernia, and sometimes simply a Meckel's diverticulum has been discov- 
ered. In rare cases the sigmoid flexure or other parts of the great bowel 
may be found. 

Secondary changes often ensue. Inflammation of the lining mem- 
brane of the sac and of the intestinal coils may lead to fibrous adhesions 
constricting the neck of the sac and binding the intestines firmly in place. 
If the contents of the hernia have receded, such inflammation may ob- 
literate the sac completely or merely at its neck, the body of the sac 
in the latter case becoming distended with serous liquid. In cases in 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



659 



which portions of omentum are included in the hernia, hypertrophic 
overgrowth of the adipose tissue may occur, and may lead to appear- 
ances not unlike those of a lipoma. 

Herniae are described as being reducible and irreducible, according 
to the ability of replacing the contents into the peritoneal cavity or not. 
Herniae become irreducible when the coils of intestine are distended by the 
accumulation of fecal matter, when fibrous adhesions have narrowed the 
neck of the sac or bound the coils firmly in place, or when additional coils 
of intestine or portions of the omentum have descended into the hernia. 

Strangulated Hernia. — This term is applied to hernise in which pres- 
sure at the neck by inflammatory exudation or constriction, or in- 
veterate obstruction by accumulating contents of the bowel, has led to 
obstruction of the circulation in the intestinal coils of the hernia. In- 
tense passive congestion, inflammation of the peritoneal covering of the 
intestines within the hernia, and, finally, gangrenous necrosis are the 
frequent results. 

INTESTINAL OBSTRUCTION 

Complete obstruction of the intestines, or ileus, may be due to in- 
ternal strangulation by bands of adhesions, to a twist or volvulus, to 
intussusception or invagination, to kinking of a part of the tube or to 
paralysis of a section of gut where the blood or nerve supply is damaged; 
the last two are usually post-operative accidents. The effects of all 
forms are illustrated in the three principal varieties to be cited. 

The symptoms and signs of ileus are essentially the same for all 
varieties, no matter what their mechanical origin may be. It cannot be 
said that their pathological physiology is fully understood but the most 
acceptable explanation today is that bacteria grow in the stagnated con- 
tents of the dilated tube, attack the stretched and congested mucosa and 
produce poisons which can be absorbed; perhaps tissue autolysis liberating 
soluble toxic primary proteoses may contribute to the intoxication. 
Experimentation would indicate that ligation of a part of the gut freed 
of bacteria is not incompatible with life. Some of the symptoms have 
been laid to the excessive discharge of fluid from the intestinal wall. It 
is noteworthy that obstruction high in the tract produces more rapidly 
appearing and severe signs" than when it affects the lower levels. 

Internal strangulation may be due to the obstruction of a coil of 
intestine by fibrous peritoneal adhesions, or by a coil slipping through 
abnormal openings or perforations in the mesentery or omentum. The 
persistence of the cord passing from the end of a Meckel's diverticulum 
to the umbilicus is an unusual cause. 

The results of internal strangulation are generally serious. Great 
dilatation occurs above the point of obstruction, the intestine below 
becoming collapsed. Great congestion and subsequently peritonitis 
occur at the point of stricture, and necrosis with perforation may ensue. 

Volvulus is the term applied to a twist of some part of the intestinal 
canal. Occasionally there is simple rotation of the bowel about its own 
axis, but more commonly a loop of intestine twists about on its mesenteric 
attachment. Abnormal laxity of the mesentery is an important pre- 
disposing cause, and may be a congenital condition, or may result from 



660 



A TEXT-BOOK OF PATHOLOGY 



the absorption of fatty deposit between the mesenteric layers. The 
immediate cause is generally strain or abdominal compression. 

The most frequent seat of volvulus is the sigmoid flexure. The 
bowel above the point of obstruction becomes distended, as in internal 
strangulation, while the coil included in the twist itself is engorged 
with blood and often presents hemorrhagic infarctions in consequence of 
obstruction of the veins in the mesentery. Gangrene of the bowel may 
result. Complete knots are occasionally observed in volvulus. 

Intussusception, or invagination, is a condition in which one part 
of intestine slips into an adjoining part, as one may invert the finger of a 
glove (Fig. 299). The upper part of the intestine is usually induplicated 




Fig. 299. — Intussusception of the small intestines (from the Vienna General Hospital 

Collection) . 

and pushed into the lower part. Irregular peristalsis, resulting from 
intestinal disorders and particularly from atony of one part with in- 
creased activity of adjoining parts, is the most fiequent cause, and con- 
tinuing in the disturbed part further propels the outer over the inner 
segment, or vice versa, as it would a mass of feces. Occasionally poly- 
poid tumors within the bowel are dragged forward by the peristalsis, 
and carry the higher part of the intestine to which they are attached into 
the lower part. Intussusception is more common in children than in 
adults, and affects the ileocecal region most commonly. Not infrequently 
multiple invaginations are found in the small intestine of children ; these 
probably occur during the death agony or postmortem. 

The portion of the gut slipping into the receiving part is called the 
intussusception; the outer or receiving section, the intussuscipiens. 

The appearance of intussusception is simply that of one part of in- 
testine pushed into the adjoining part, with secondary inflammatory and 
congestive changes. Most frequently invagination begins at the ileo- 
cecal region, the valve and ileum being carried forward into the ascending- 
colon. Very rarely the ileum itself invaginates through the valve. Oc- 
casionally the ileocecal valve may be carried through the colon and 
rectum and present externally. 

The extent to which the inner portion can slip into the envelope will 
depend upon the length of the mesentery and the freedom with which the 
circulation is maintained. If this membrane be loose and no constric- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



661 



tion of vessels occur, long invaginations arise but usually the blood stream 
is suddenly cut off, edema and congestion occur and the enclosed portion 
of intestine becomes gangrenous; in such instances acute symptoms of 
ileus rapidly develop. When the circulation remains fairly good, the 
adjoining serous surfaces of the invagination tend to unite by peritonitis, 
and the intussuscepted portion may become gangrenous and be discharged 
with re-establishment of the lumen. If peritonitis has established union 
between the ensheathed and the ensheathing section of the gut, recovery 
may ensue. Otherwise perforation leads to fatal peritonitis. 

PROLAPSE OF THE RECTUM 

Prolapse of the rectum in consequence of weakness of the sphincter 
and other parts of the wall, together with repeated straining, is a common 
condition in infants, and is occasionally met with in adults. In children 
any form of diarrhea may be complicated by prolapse; in adults chronic 
proctitis is the most frequent cause. The weakened condition of the 
sphincter in proctitis furnishes the predisposition, and the characteristic 
tenesmus of the disease is the immediate cause. Prolapse may be only 
an occasional condition, or may be constant. Secondary inflammation, 
ulceration, and even necrosis of the prolapsed portion may occur. 

ATROPHY AND DEGENERATIONS 

Atrophy of the mucosa ls frequently met with as a part of chronic 
enteritis in its later stages. This is especially marked in young children 
suffering from chronic intestinal catarrh and marasmus. Occasionally 
atrophy of the mucosa or of all of the coats of the intestines may occur 
as an independent affection, or as the result of marantic or cachectic 
conditions. 

Pigmentation may be due to hemorrhages in the mucosa or sub- 
mucosa, and not infrequently after intense hemorrhagic inflammation 
the bowel may be quite black from the deposit of hematogenous pigment. 
Brownish pigment deposited in the muscle-cells, analogous to that of 
brown atrophy of the heart, is occasionally observed in old and cachectic 
individuals. Similar pigmentation of the muscle-cells and also of the 
submucosa or mucosa, of even more decided character, occurs in youthful 
persons addicted to alcohol. The intestines alone may be thus affected, 
or the liver, spleen, lymphatic glands, and skin are simultaneously in- 
volved. The term hemochromatosis (q. v.) has been proposed for this 
condition. It is said that pigmentation of the colon may result from 
absorption of bile derivatives. Pick accounts for some of the obscure 
pigmentations of the colonic mucosa by assuming a deposit of melanin- 
like bodies, probably protein digestion products under the influence of 
tyrosinase. The blackish deposits of iron-free matter sometimes seen 
in the lymphatic tissue are explained by Lubarsch as absorption of 
swallowed coal particles. 

Amyloid infiltration is met with in association with amyloid dis- 
ease of the liver, kidneys, or spleen, and particularly in cases in which 
there is tuberculous ulceration of the intestines. The mucous mem- 
brane is principally involved, and becomes somewhat hardened and pre- 
sents a peculiar grayish luster. Superficial erosions and even ulcers may 



662 



A TEXT-BOOK OF PATHOLOGY 



result. The process begins, as elsewhere, in and around the small blood- 
vessels. 

CIRCULATORY DISTURBANCES 

Active hyperemia may occur from acute irritation, and forms a 
part of inflammation. 

Passive hyperemia results from causes similar to tho^e producing 
congestion of the stomach. Among these, obstructive diseases of the 
liver, notably cirrhosis, and cardiac and pulmonary affections are most 
prominent. The intestinal mucosa becomes somewhat swollen, ofttimes 
edematous, dark bluish-red in color, and occasionally marked by 
punctate hemorrhages. The mesenteric veins are widely dilated. Occa- 
sionally hemorrhagic liquid is found within the intestines, the points of 
hemorrhage remaining undiscovered. 

Hemorrhage. — Petechise are found in many cases of violent septic 
or infectious diseases, in intense anemias, and as the result of marked 
passive hyperemia. Embolism in cases of ulcerative or malignant endo- 
carditis may lead to petechial hemorrhages, and the same are observed 
as a part of the morbid anatomy of intestinal anthrax. Large intestinal 
hemorrhages may occur from typhoid, tuberculous, dysenteric, or syph- 
ilitic ulcerations, or from the perforation of a large arterial branch by a 
peptic ulcer in the duodenum. Hermorrhoids may occasion consider- 
able hemorrhages from the rectum. 

Edema of the mucosa may result from passive congestion, and at- 
tends acute or chronic inflammations, especially the more intense forms. 

Embolism and thrombosis of the mesenteric arteries are rare 
conditions, due most often to cardiac embolism, but also to arteriosclero- 
sis in loco and to downward thrombosis from the portal vein. Embolism 
may lead to hemorrhagic infarction because of some inadequacy of the 
anastomosis of the mesenteric vessels, which usually is rich. The re- 
sult is a stretch of paralyzed, reddened, and swollen gut within which 
hemorrhage and, later, sloughing occur, corresponding to the distribu- 
tion of the occluded vessel. 

Hemorrhoids result from varicose enlargement of the veins of the 
rectum. They are usually found in the lower part of the rectum, inside 
or outside the sphincter, and a distinction is made between internal and 
external hemorrhoids. 

Etiology. — Obstruction of the venous circulation is the important etio- 
logical factor. It may be due to chronic diseases of the liver (cirrhosis), 
repeated pregnancies, pelvic tumors, or chronic constipation with fre- 
quent retention of feces in the rectum. The last-named condition acts 
in a twofold manner. On the one hand, it causes venous obstruction, 
and, on the other hand, chronic proctitis, which in turn occasions disease 
of the veins of the rectum, and thus predisposes them to dilatation. In 
all cases of hemorrhoids, constipation and the resulting proctitis are im- 
portant as auxiliary causes. The anal veins are poorly supported by 
connective tissue, so that when the sphincter contracts it holds the blood 
within the distended vessels. Hemorrhoids are rarely met with before 
adult age. 



DISEASES OF THE GASTRO-INTESTINAL TRACT 



663 



Pathological Anatomy. — -The hemorrhoid presents itself as a small 
polypoid elevation of more or less congested appearance. On section it 
is found to be highly vascular and to consist of dilated veins. There 
may be a congeries of slightly enlarged veins or cavities of considerable 
size. Between the veins there is more or less abundant inflammatory 
connective tissue. Thrombosis often occurs within the cavities; and 
occasionally the fibrous tissue around them undergoes active prolifera- 
tion, when a structure resembling a fibro-angioma results. Hemorrhagic 
extravasations may occur from the veins, and free hemorrhage from the 
surface is a common symptom. Infective inflammation and phlebitis of 
the veins sometimes occur, in which cases the hemorrhoid enlarges and 
becomes inflamed and edematous. Inflammation of the adjoining tissues 
may occur (proctitis, periproctitis). 

Hemorrhoids may cause marked anemia by the repeated hemorrhages, 
and sometimes occasion septic infections when they have themselves 
become infected and inflamed. 

Other varices may arise in the intestines, as, for example, in cirrhosis 
of the liver. 

INFLAMMATIONS 

Inflammation of the intestines, or enteritis, may affect any part 
of the intestinal canal, and involve the mucosa and submucosa more 
particularly. It is more frequently present in children and in the aged 
than at other periods of life. 

Etiology. — The causes of enteritis are similar to those of gastritis, 
and among them may be reckoned all forms or irritating foods or foreign 
matter taken with the food. Poisons of various kinds operate in a 
similar manner. In many cases the irritant poisons which occasion 
enteritis are developed within the body in consequence of improper 
digestion and fermentation. Bacteria play an important role in this 
process, and are themselves the direct cause of enteritis in instances in 
which improprieties of diet or digestive disturbances have furnished 
favorable conditions for their growth and multiplication. The normal 
colon bacillus is perhaps the most frequent and important microorgan- 
ism of ordinary non-specific enteritis, but other organisms doubtless 
frequently play a part. The colon bacillus probably increases in viru- 
lence under certain conditions and then occasions irritation. 

The bacteria of the intestines comprise many species, chiefly sapro- 
phytic, but which may under appropriate circumstances cause enteritis. 
They are engaged in fermentation and putrefaction, the two forces being- 
balanced in the normal state. "When, however, one or the other is ex- 
cessive, it reduces the natural protective forces. The normal intestinal 
wall and juice are protective, but if disturbed are attacked either by the 
normally present germs or others to whose entrance in food the dam- 
aged organ offers no resistance. The mechanical conditions mentioned 
in the discussion of bacteria in the stomach play a similar role in the 
intestines. 

Pathological Anatomy. — There are a number of varieties of enteritis, 
and different types may be described, though individual cases rarely 



664 



A TEXT-BOOK OF PATHOLOGY 



conform to a single variety. Of the acute forms of enteritis, the impor- 
tant are the catarrhal, suppurative, and the pseudomembranous. 

Catarrhal enteritis may effect any part of the intestinal tract. The 
mucosa is swollen and usually light-red in color; the arteries are visibly 
distended, and not rarely there are petechial hemorrhages. The surface 
is covered with mucous exudate containing desquamated and degenerated 
epithelial cells and emigrated leukocytes; while the intestinal contents 
are rendered liquid by serous exudation. The solitary follicles or 
agminated collections of lymphoid tissue may be particularly swollen 
and cause projections above the surrounding mucosa. The term follicu- 
lar enteritis is applied to such cases (Fig. 300). In other instances the 
desquamation of epithelium is more prominent than the mucous exuda- 
tion, and considerable shreds of mucosa may be loosened and discharged. 
The term croupous enteritis is suggested by such conditions. 




Fig. 300. — Hemorrhagic follicular enteritis. 



The so-called toxic enteritis, such as is seen in toxic (not bacterial) 
meat-poisoning, is of the catarrhal type, with much hyperemia and 
edema. Superficial necrosis or hemorrhage may occur. 

Suppurative enteritis differs from the catarrhal form in the greater 
degree of emigration of leukocytes. The exudate upon the surface may 
be largely composed of white corpuscles, and in intense cases the surface 
may be covered with almost pure pus. Round-cell infiltration of the 
mucosa and the submucosa is present, and focal collections leading to 
submucous abscesses or to ulcers upon the mucous surface are occasionally 
seen. The solitary follicles are enlarged and tend to break down, form- 
ing follicular ulcers. 

Pseudomembranous enteritis is characterized by the formation 
of a grayish membrane upon the surface of the intestine. The large 
intestine is more frequently involved, and the process is especially met 
with in dysentery (see p. 670). True diphtheria of the bowel with 
pseudomembranous deposit may sometimes occur. 

The term ulcerative enteritis is sometimes used, but, as a matter of 
fact, non-specific ulcerations are relatively rare. Eiosions are commoner. 
It is better to speak of the pathological type of enteritis with ulceration, 
as the ulcerative forms are considered under typhoid, tuberculosis, and 
the like. Ulceration of the intestines occurs in a variety of conditions. 



DISEASES OF THE GASTROINTESTINAL TRACT 



665 



Peptic ulcers, similar to those met with in the stomach (q. v.), are occasion- 
ally found in the duodenum, and are there explained as given for gastric 
round ulcer. They have the same characters and tendencies as those of 
the stomach; they may occasion sudden death from hemorrhage. Ulcers 
in the duodenum are also an occasional result of extensive burns of the 
skin; and attention has been called to the frequency of duodenal ulcera- 
tion in cases of chronic Bright 's disease. Ulcerations of the ileum are 
habitual in typhoid fever and tuberculous enteritis, and are occasionally 
due to anthrax or actinomycosis. Ulcers may be found in all forms of 
enteritis of childhood, especially in intense forms and in cases com- 
plicating the exanthemata. Sarcomata and carcinomata are rare causes. 
Ulcerations of the large bowel are met with in chronic colitis and dys- 
entery. A form of peculiar clinical interest is anal fissure. This is a 
linear ulceration of the rectum in the region of the sphincter. It may 
be associated with hemorrhoids or may be independent. 

Chronic enteritis results from acute attacks or from repeated irri- 
tation. Chronic congestion in consequence of hepatic or cardiac affec- 
tions is a predisposing cause of importance. 

In the early stages the mucous membrane is usually more or less 
swollen, and sometimes proliferative changes in the glandular elements 
may lead to distinct polypoid elevations. These are especially pro- 
nounced in cases in which the healing of ulcers of acute enteritis has 
occasioned cicatricial constrictions and thus elevated .adjoining parts 
of the mucosa. The elevated portions may undergo proliferative in- 
flammation, and polypoid formations result. In the later stages of 
chronic enteritis atrophy may ensue, in part as the result of the over- 
growth of the stroma of the mucosa and the degeneration of the glandu- 
lar elements, in part also as the result of the over distention or tympany 
resulting from fermentation of the intestinal contents. This atrophy 
may affect the mucous membrane alone, but more commonly also in- 
volves the muscularis. Hyperplastic processes in the lymphoid ele- 
ments may be a prominent feature in the hypertrophic stage of chronic 
enteritis, and may give place to atrophy in the later stages. On the other 
hand, the enlargement of the solitary follicles and Peyer's patches may 
persist for a long time after atrophy has led to great thinning of the 
remaining portions of the mucosa. 

Pathological Physiology. — Enteritis may occasion profound dis- 
turbances in a variety of ways. In cases of infective character general 
systemic intoxication may result from the absorption of bacterial prod- 
ucts or substances resulting from decomposition of the intestinal con- 
tents. In other cases the intensity of the local irritation may, through 
the nervous system, occasion great depression or shock; and subse- 
quently the exudations into the intestines may cause depletion of the 
vascular system and failure of the circulation. The local effects and the 
resulting behavior of the bowels differ in different cases. Sometimes 
the peristaltic movements are arrested by the intensity of irritation and 
obstinate constipation results; more frequently hurried peristalsis and 
the abnormal exudation (serous or mucous) occasion diarrhea. The 
digestive processes fail from the diseased condition of the bowel r as well 
as from the rapid peristalsis and premature discharge of the intestinal 
contents; more or less profound disturbance of health results. 



666 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS OF SPECIAL PARTS 
Duodenitis occurs in association with gastritis from irritating 
food and the like. The appearances are the same as in gastritis. Duo- 
denitis is prone to occasion obstruction of the terminal portion of the 
common bile-duct by the inflammatory thickening of the mucosa and 
-the accumulation of mucus in the mouth of the duct, and in this way 
gives rise to obstructive jaundice (catarrhal jaundice). The inflamma- 
tion may extend into the liver or pancreas along the respective ducts. 

Inflammation of the ileum presents no special characteristics, ex- 
cepting that enlargement of the follicles (follicular enteritis) is fre- 
quently conspicuous. Follicular ileitis is particularly common in 
children suffering from infectious fevers, such as diphtheria and scarla- 
tina. Peyer's patches may be considerably enlarged and even ulcerated. 
The ulcers are generally small, and several may occur in a single Peyer's 
patch instead of single ulcers, such as occur in typhoid or tuberculous 
enteritis. It is a curious fact that some of the lymph-follicles may be 
free from gross alterations even in severe follicular enteritis. 

Typhilitis or cecitis (inflammation of the cecum) may be due to 
the irritation of the intestinal contents in consequence of constipation 
(stercoral typhlitis). This affection is probably very frequent, though it 
leads to no severe consequences and occasions no urgent symptoms. 
Typhlitis is probably generally of the simple catarrhal variety, but in 

obstinate constipation or obstruction 
of the colon ulceration may occur. 
_ Perforation or extension to the sur- 

i rounding tissues (perityphlitis) is the 
jfo rarest of all consequences. Usually 
y the latter is secondary to inflamma- 
V tions of the appendix vermiformis. 
jj Appendicitis may be a primary 
■jj condition, or it may result from 
- 'J primary typhlitis or cecitis. The 
•' inflammation of the mucosa of the 
y cecum may extend directly to that 
of the appendix; or may cause ob- 
struction of the mouth of the appendix 
Fig. 301.— Acute follicular and catar- in the same manner as duodenitis 

rhal appendicitis showing swelling of causes obstruction of the Common 

lumen* gfeat en ° USh t0 obliterate the bile-duct. There results a retention 

of the contents of the appendix and 
multiplication with increase in virulence of the contained bacteria 
(Bacillus coli communis, staphylococcus, streptococcus, and others). 
The mucosa of the appendix, rendered less resistant in consequence 
of the overdistention and associated congestion, may be penetrated 
by the micro-organisms and appendicitis results. There may be 
some slight defect in the surface epithelium into which the bacteria 
pass. Superficially there is little change, but it is characteristic of 
the appendix that lesions spread into the deep layers to a greater ex- 
tent than on the surface. This deep spread is probably due to early 
if not primary involvement of the lymph tissue, which in swelling ob- 




DISEASES OF THE G ASTRO-INTESTINAL TRACT 



667 



structs the lumen of the tube and creates recesses within which bac- 
teria multiply. In many cases fecal concretions are found within the 
appendix, and less commonly foreign bodies of various sorts have been 
found. These have been assumed to be the direct cause of the disease, 
but seem to be important" only to the degree that they obstruct the 
lumen with retention of secretion. On the other hand, there is much 
reason to believe that the fecal concretions are often formed in con- 
sequence of the accumulation of mucous and desquamated epithelial 
cells and the stagnation of the contents of the appendix, in recurring mild 
attacks. From many sources the oxyuris has been held as an important 
predisposing foreign body but its exact frequency and role are not 
yet known; it is probably more common in young persons than formerly 
believed. The position of the appendix and rapid swelling of its mucosa 
favor retention of foreign bodies and exudates, while its movability 
renders kinking easy; this bending increases in importance with its 
duration and sharpness, for passive congestion and edema thus occa- 
sioned favor bacterial growth in the mucosa. Typhoid and tuberculous 
ulcers and actinomycosis have been found in the appendix. These 
lesions may occasion secondary appendicitis of an ordinary sort, or they 
may in themselves cause the symptoms of appendicitis. Obstruction 
of the arterial supply of the appendix was formerly regarded as an im- 
portant element in the etiology, but probably is only of secondary im- 
portance. Infection of the organ by embolism of bacteria is probably 
rare, although it doubtless can occur. Appendicitis is less frequent 
in women than in men. This has been ascribed to the existence of a 
more' adequate blood-supply (the supplemental part derived from the 
ovary) in women. 

The pathological anatomy of appendicitis varies in different cases, 
and we may, for convenience, distinguish a catarrhal, a necrotic or gan- 
grenous, and an interstitial form. 

In the mildest or catarrhal form there is merely retention of the 
contents of the appendix and slight disease (swelling and erosion) of the 
mucosa. The muscularis and serous coat may be congested and edema- 
tous, but are not extensively involved. The contents of the appendix 
are more or less mucopurulent in character, and may, of course, become 
pure pus. This form may proceed into a purulent or phlegmonous 
variety with active puriform exudation into the wall and lumen, softened 
yellow wall and the early appearance of fibrinous peritonitis over the 
serosa. Such a lesion is more often local than general for the latter is 
usually a part of or a forerunner of the most serious form of the disease 
next to be consideied. Such local purulent areas may however, lead 
to perforation or peritonitis without sloughing of the whole organ. 

In the necrotic or gangrenous form the mucous membrane sutlers 
rapid destruction and the muscular and serous coats are quickly in- 
vaded. Fibrinous peritonitis soon develops in the serous coat and 
over the adjacent intestines, either as a result of penetration of bacteria 
through the walls of the appendix, or in consequence of perforation 
of the walls. The local peritonitis serves the purpose of restraining the 
infective disease and prevents diffuse peritonitis. In cases of rapid 



668 



A TEXT-BOOK OF PATHOLOGY 



gangrene, with early rupture or escape of abundant bacteria, general 
peritonitis may result before a restraining wall can be formed. 

The term " interstitial appendicitis" may be used to designate 
cases in which all of the coats of the appendix are involved and in which 
there is a special tendency to productive changes in the connective 
tissues. In reality, all cases of appendicitis show more or less interstitial 

change of this character (Fig. 302), 
but in some it is the conspicuous 
feature. These cases frequently 
terminate in chronic thickening of 
the appendix. 

Results. — -Mild cases of catarrhal 
appendicitis may subside after free 
purgation, with relief of the obstruc- 
tion at the mouth of the appendix. 
In more serious inflammations and 
in cases in which the obstruction 
remains, the disease spreads through 
the walls of the appendix to the 
peritoneum and occasions local peri- 
tonitis; or rupture of the appendix 
occurs, and more intense local or 
general peritonitis follows (Figs. SOS- 
SOS) . In either case fibrinous deposits 
are formed upon the peritoneum, and 
not rarely a localized abscess (periap- 
pendiceal abscess) results. The ap- 
pendix itself may be separated from 
the cecum, and may lie free in the 
abscess, or it may be firmly embedded 
in the fibrinous wall of the abscess. 
The latter may subsequently undergo 
inspissation, but more commonly 
ruptures into the general peritoneal 
cavity, into some part of the intestines, 
into the ureter, bladder, or externally. 
In cases with favorable outcome the 
appendix is usually bound down by 
adhesions which attach it to neigh- 
boring coils of intestine or to other 
structures. The appendix in such 
cases is usually distorted and greatly 
thickened, and repeated attacks of inflammation (relapsing or recurring 
appendicitis) are not unusual. Chionic appendicitis may arise in 
this manner, that is, as a remnant from an acute process; but it 
also occurs without involvement of the peritoneum, the lesions being 
confined to the appendiceal mucous and muscular layers. Chronic 
appendicitis may be divided into the catarrhal and sclerosing forms. In 
the former type we have alterations in the structure of the inner coats 
as the most prominent change, while in the sclerotic form connective- 




Fig. 302. — Acute appendicitis, with 
round-cell infiltration and hyperplasia 
of connective tissue in all of the coats. 
In large part the round cells of the 
mucosa and submucosa belong to the 
normal lymphoid tissue of these parts. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



669 



tissue overgrowth occurs throughout all coats, so that finally, by con- 
traction, the glandular structures are destroyed, and the organ becomes 
a fibrous cord (obliterating appendicitis). 

There is generally more or less systemic intoxication and infec- 
tion with appendicitis, and degenerative changes and metastatic ab- 
scesses may be found in distant organs. Not rarely pylephlebitis and 
metastatic abscesses of the liver are encountered. 




Figs. 303-305. — Ulcerative and perforative appendicitis, showing perforations; two fecal 
concretions from other cases of appendicitis (modified from Bollinger) . 

Colitis, aside from the specific form (dysentery), is most frequently 
due to irritation by fecal accumulations, and the sigmoid flexure is the 
common seat. The entire colon may, however, be involved. It may 
assume catarrhal, ulcerative, pseudomembranous, purulent, hypertrophic 
and nodular forms in which the gross and minute pathology is the same as 
for the intestine as a whole. The bacterial causes are not certainly known 
but are probably numerous, while poisons and other irritants doubtless 
play a part. A condition of clinical importance is mucous colitis, prob- 
ably not actively inflammatory in its early stages but later showing some 
chronic inflammation. Swelling of the mucosa by abundant mucus for- 
mation, which appears as a more or less tenacious covering, appears early, 
while in the later stages atrophy and thinning are observed. Ulcerations 
are not uncommon. When the mucous exudation and the desquamated 
cells accumulate upon the surface the appearance of a pseudomembrane 
is simulated, and casts of the bowel or masses of mucus may be discharged 
from time to time. 

Proctitis, or inflammation of the rectum, may be due to direct 
irritation by retention of fecal matter, by parasites, or by toxic agents; 
or it may occur secondarily after various other diseases of the rectum, 
such as tumors, hemorrhoids, and the like. The inflammation tends to 
become chronic. The rectum is generally involved with the colon in 
cases of mucous colitis. 



670 



A TEXT-BOOK OF PATHOLOGY 



The mucous membrane is considerably swollen, often edematous, 
and usually presents petechial hemorrhages. Ulceration may occur 
secondarily, and extension of the ulcerative process to the surrounding 
tissues (periproctitis) is not unusual. In the latter cases fistulous com- 
munication may be established between a perirectal abscess and the 
rectum (incomplete fistula), or a fistulous communication may form be- 
tween the rectum and the exterior (complete fistula in ano) . Sometimes 
proctitis is secondary to periproctitis occurring in diseases such as typhoid 
fever, pyemia, and the like. 

INFECTIOUS DISEASES 

Dysentery is a name applied to two varieties of infectious, colitis 
whose etiology is now quite definitely accepted. One form, bacillary 
dysentery, is due to a non-motile bacillus of typhocolon morphology 
(see p. 311), while the other form, amebic dysentery, is caused by a pro- 
tozoon, Entamoeba histolytica (see p. 382). 

Bacillary dysentery is a communicable colitis, presenting acute, 
subacute, or chronic characters, due to one of the varieties of the Bacillus 
dysenterice. It appears as epidemics in the tropics, in camps and insti- 
tutions, or may occur sporadically. It seems to be a general infection 
in the acute cases, but there is rarely a bacteremia, except shortly be- 
fore death. The bacteria may at times find their way to the lymph- 
glands draining the affected bowel. Rare instances of septicemia are 
reported. The hygiene and bacteriology have already been discussed. 

The morbid lesions are usually confined to the colon, but may at times 
extend to the ileum. In the large gut the whole length is usually in- 
volved in, at first, a congestive and mucocatarrhal inflammation. This 
is rapidly overshadowed by a superficial necrosis which affects the tips 
of the rugae. Great swelling of the mucosa enlarges and distorts these 
folds. Over the mucous surface there appears a delicate necrotic film 
which can be rubbed away by the finger, leaving erosions or ulcers which 
may remain superficial but often penetrate quite deeply and become 
undermined. This of course means that the whole mucosa may be in- 
volved but the tendency is for the bacillary process to remain more 
superficial than the amebic. In fulminating cases the mucosa becomes 
hemorrhagic or even gangrenous. In subacute and chronic cases these 
changes are not so intense, the follicles being more involved and becoming 
prominent, areas of pigmentation appearing and the whole mucosa, 
distorted and hypertrophic by connective tissue increase, being rugous 
or even polypoid. Regeneration of the mucosa only occurs after mild 
attacks, cicatrization appearing after severe ones. 

Amebic dysentery is a communicable colitis, usually chronic, but at 
times acute, due to Entamoeba histolytica, endemic in some tropical and 
subtropical countries, occasionally appearing in epidemic or sporadic 
forms in higher latitudes, and showing a great tendency to involve the 
liver with abscess formation. It is commonest among white male adults. 

The lesions are usually confined to the upper colon, although the 
sigmoid and rectum are often involved. When the amebse penetrate the 
mucosa they infest the submucosa, causing great swelling and thicken- 
ing by edema, round-cell infiltration, and proliferation of fixed tissue 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



671 



cells. This swelling interferes with the nutrition of the overlying mu- 
cosa, and ulceration is early and extensive; the infiltration is so wide- 
spread and rapid in its extension that intercommunicating swellings, 
and then undermined ulcerations, are produced. The ulcers are of all 
conceivable shapes, and as the infiltration or destruction in the sub- 
mucosa is greater in extent than the loss of surface, mucous membrane 
bridges only may separate the superficial defects. Penetration to the 
muscular or serous coats is known, and perforation is sometimes seen. 
Healing occurs by granulation tissue, beginning around the base of the 
ulcer. 




Fig. 306. — Amebic dysentery, active stage showing ulcers, bare and covered by sloughs, 
hemorrhagic areas and generally thickened colonic wall. 

Microscopically, the infiltrate is of round and tissue cells, and few 
polynuclears are found. Eosinophiles are common. The character- 
istics of amebic dysentery are the marked infiltration and thickening 
of the submucosa, in which lie amebse occupying spaces in the cellu- 
lar collections, and in lymph- or small blood-vessels. The liver lesions 
consist of single or multiple abscesses, or focal necroses with paren- 
chymatous degenerations. Abscesses occur chiefly in the right lobe near 
the colonic or diaphragmatic surface. The contents vary from serous 
to a reddish-brown, puriform, necrotic material, in which, near the wall, 



672 



A TEXT-BOOK OF PATHOLOGY 



amebse may be found. This wall consists of a layer of dense tissue cell 
proliferation and infiltration of round cells, with great congestion about 
it. These abscesses may rupture, the commonest direction being through 
the diaphragm to pleura and lung. 

Cholera. — Cholera epidemica or Asiatica is an acute specific in- 
flammation of the small and large intestines due to the comma bacillus 
or vibrio of Koch. This micro-organism is found in the great majority 
of cases, but occasionally it is not discovered, while other micro-organ- 
isms, Bacillus coli communis and streptococci, are present. It is probable 
that in these instances errors of observation cause the failure of detection. 

Pathological Anatomy. — Cholera is characterized by redness and 
swelling, and not rarely by petechial ecchymosis of the mucous mem- 
brane, particularly of the small intestine (ileum). The superficial epi- 
thelium suffers early an extensive degeneration, perhaps a form of 
coagulation necrosis. The solitary follicles and the agminated glands may 
enlarge and may suffer ulceration. The intestines contain and discharge 
a serous exudation, often in large quantities, in which are grayish or 
whitish particles, consisting of flakes of desquamated and degenerated 
epithelium. The term " rice-water discharges" is applied to the evacua- 
tions. Extensive areas of the mucous membrane may be laid bare by 
the desquamation of the epithelium. When cholera has passed to its 
later stages, secondary pseudomembranous inflammation of the mucous 
membrane is not unusual, and is probably the result of secondary infec- 
tion. 

Associated Conditions.- — The blood is thickened and dark red in 
color; thrombosis in the heart or venous sinuses is frequent. These are 
due to the great loss of water by the diarrhea. The kidneys present 
marked congestion and degeneration, which are dependent upon the 
action of the toxins of the disease. Lobular pneumonia is a common com- 
plication. There is apt to be a slight fibrinous peritonitis, while the gut 
itself is thin and atrophic. 

Typhoid fever is distinguished by an acute, specific inflammation 
of the lymphoid elements of the intestines particularly of the ileum and 
upper portion of the colon (Figs. 307-309). The specific cause is the 
Bacillus typhi abdominalis, described by Eberth and Gaffky. This or- 
ganism enters the gastro-intestinal tract with drinking-water, milk, or 
other food, and multiplies in the small intestine (see page 304). 

Pathological Anatomy. — The specific lesions of typhoid fever occur 
in the lymphatic structures, notably in the solitary follicles, Peyer's 
patches, mesenteric glands, and spleen. It is, however, wise to remem- 
ber that a few cases of typhoid bacillus infection giving a Widal reaction, 
but without intestinal lymph-gland ulcers, have been observed, or with 
only small atypical mucous membrane lesions. The bacteremia and 
parenchymatous lesions may be otherwise as typically described. 

The solitary follicles and Peyer's patches of the lower end of the 
ileum are first affected, but later, or exceptionally in the beginning ,the 
Lymphoid collections of the upper part of the ileum and jejunum, or of 
the cecum and colon, may be involved. At first the follicles and patches 
are swollen and somewhat reddened by congestion. Within a few days 
of the onset, however, they lose their congested appearance and^pre- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



673 



sent themselves as grayish or white elevations projecting from one 
to several millimeters above the surface (Fig. 307). Microscopically 
the lymphatic tissues are found in such a state of hyperplasia that the 
topography of follicles and sinuses may be entirely destroyed, the sec- 
tion being composed of tightly packed round cells, most of which are small 
lymphocytes but many are large cells with vesicular nuclei frequently 




Fig. 307. — Typhus abdominalis : medullary Fig. 308. — Typhus abdominalis: ulcers 

swelling. with slough removed. 

containing red blood cells, bacilli or granules; not only are these latter 
found here but they have been discovered in the lymphatic channels 
at some distance from the local lesions, as well as in the mesenteric glands 
and in distant parts. These cells increase in number, and may in some 
areas outnumber the small round cells. They are similar to the large 
mononuclear wandering cells and have been discussed repeatedly. 
Their origin is far from settled but perhaps in these lesions the argument 
of Mallory that they are derived from lymphatic and vascular endothe- 

43 



674 



A TEXT-BOOK OF PATHOLOGY 



lium is most acceptable if for no other reason than the fact that along 
lymph channels and blood capillaries there is swelling of lining cells 
sufficient at times to close their lumen. The typhoid bacillus seems to 
have the power to stimulate such cells everywhere. 

The mucosa about lymph nodes usually shows congestion, thus 
making the swollen pale patches fairly prominent. The dense cellular 
packing gives a pale color to this stage of medullary infiltration, which 




Fig. 309. — Typhus abdominalis: superficial necrosis. 



remains unchanged for some days or a week. After the first week necrosis 
is prone to occur. The center of the solitary follicles or part of the 
Peyer's patch becomes more and more soft and yellow, or sometimes 
reddish from absorption of blood-pigment. The necrotic portions 
are discharged after a few days, leaving an ulcerated surface of regular or 
irregular outline, and presenting overhanging necrotic edges with hemor- 
rhagic infiltration (Figs. 309-312). Sometimes not all of the swollen 



DISEASES OF THE GASTROINTESTINAL TRACT 675 




Fig, 311. — Typhoid fever. Swelling of lymph-follicles, cross-section of Peyer's patch 

(Karg and Schmorl). 




Fig. 312.- — Typhoid fever, slough formation, showing edge of Peyer's patch becoming 
necrotic. The mucosa to the right shows catarrhal inflammation which usually accom- 
panies the follicular lesions (Karg and Schmorl). 



676 



A TEXT-BOOK OF PATHOLOGY 



glands slough away, and a knobby or granular appearance results from 
the retention of isolated lymph-follicles. This necrosis has been laid to 
the toxins of the bacillus, to the anemia resultant upon close packing of 
the cellular infiltrate and to closure of capillaries by endothelial swelling; 
perhaps all these factors are operative. 

The ulcers resulting from destruction of the solitary follicles are 
small and rounded, while those involving the Peyer's patches are elon- 
gated, the long axis being parallel with the axis of the intestine. The 
bases are smooth except, perhaps, for muscular ridging. The ulcers 
are usually found in an acute stage at the end of the second or at the 
beginning of the third week of the disease. Resolution may occur with- 
out necrosis and ulceration, but more commonly ulcers are formed and 
healing proceeds more slowly. When a lymph node collection has been 
entirely destroyed, regeneration does not occur, but a scar appears, 
curiously enough practically never leading to constriction and narrowing 
of the gut. The inner wall of the intestine at the area is lower than its 
surroundings, epithelium growing over the fibrous tissue supplied 
by the submucosa to cover the muscle. More commonly some small 
follicles is left and regeneration of the patch is attempted from this as a 
center. The result is however usually a somewaht distorted representa- 
tion of the original plaque. When the lymphoid follicles of the patches 
have become necrotic and have been infiltrated with blood, dark pigmented 
spots are formed, and give rise to the condition designated as the "shaven- 
beard" appearance. 

Complications. — Extensive necrosis may lead to erosion of a blood- 
vessel and hemorrhage; or the wall of the intestine may be completely 
perforated by the necrotic process, and fatal peritonitis may result. 
In other instances peritonitis occurs without perforation by direct 
extension of the inflammatory process through the intestinal wall. 
Very commonly slight reactive peritonitis is found on the serous surface 
opposite the ulcers. Extensive peritonitis rarely occurs in this way. 
Peritonitis in rare instances results from necrosis of the mesentery 
glands, or from rupture of the spleen. 

The mesenteric glands are characteristically enlarged, those nearest 
the points of ulceration being first and most prominently, involved. 
In the first stage they are soft and dark red in color, exuding a small 
amount of liquid on section. Later, they become larger, harder, and of 
whitish appearance; they may finally suffer necrosis and rupture. 
Usually, however, resolution takes place after the first stage. Micro- 
scopically they resemble the lesions in Peyer's patches. 

The spleen is enlarged in most cases, and presents the characteristics 
of acute splenic tumor. The peculiar features in this disease however 
lie in the really enormous numbers of red blood cells that everywhere 
pervade the splenic tissue, giving to it the characteristic red color, and 
the presence of endothelioid cells, diffusely and in groups, which are 
actively phagocytic for the erythrocytes. Very rarely perisplenitis 
or abscess may occur. In the bone-marrow there is an increase of the 
small round and large phagocytic endothelial cells, a relative decrease 
of polynuclears, and occasionally necroses. 



DISEASES OF THE GASTROINTESTINAL TRACT 



677 



Lesions in Other Parts. — -The muscles, particularly those of the 
abdominal walls, frequently show spots of degeneration of a waxy or 
hyaline character, as described by Zenker. Very rarely petechial or 
considerable hemorrhages may be found in the muscles; and abscesses 
are sometimes met with as sequelae. 

The heart muscle is involved in perhaps a majority of the cases. 
The muscle-fibers suffer parenchymatous and hyaline degeneration, and 
less commonly the intermuscular tissues present the characteristics of 
acute myocarditis. Acute endocarditis and inflammations of other 
serous surfaces are rare in typhoid fever as compared with some other 
infectious diseases. It has been thought by some that typhoid fever 
is potent in the etiology of arteriosclerosis because small vessels are apt 
to show intimal changes (Thayer). Acute endarteritis does occur some- 
times while acute phlebitis of the iliac and mesenteric veins is not uncom- 
mon. 

Acute degeneration of the kidney and acute nephritis are quite 
common, and the kidney substances may present small lymphomatous 
foci some of which go on to necrosis at times. 

In the liver one finds, usually only on microscopical examination but 
occasionally visible to the naked eye, areas of mononuclear cell accumu- 
lation and of necrosis. The former have been described as hyperplasias 
existing lymphoid collections and as transplanted groups of mononuclears 
from the intestinal lymph nodes, and the latter as necroses of liver 
cells or of the mononuclear collections. Since it seems possible to trace 
gradations of the cellular groups into necrotic areas, it is probable that 
they are but stages of the same process. Mallory describes them as 
due to swelling and multiplication of vascular and lymphatic endothelia 
locally and to the transfer of endothelial cells from the intestinal lesions. 
They lie usually in the interstitial supporting tissue of the organ or in the 
outer zones of the lobules. True necroses of the liver cells do occur. 
The biliary channels may be infected in typhoid, usually it is believed, 
from the general bacteremia rather than directly from the intestine. They, 
with the gall bladder, form the locality in which carriers hide their 
bacilli. Gall stones have been known to contain typhoid bacilli. 

Acute lobular pneumonia and . croupous pneumonia are frequent 
complications, particularly of the posterior parts of the lung; probably 
this is due to hypostatic congestion from prolonged illness. Pleuritis is 
not common but does occur and 0. H. P. Pepper has described a case 
in which the large mononuclears, phagocyting red blood cells, were 
very numerous; the exudate is apt to be hemorrhagic. Lesions in the 
osseous system usually take the form of a purulent cortical osteitis with 
productive periostitis. 

The blood in typhoid fever, unlike other infections, present no 
leukocytosis, but, on the contrary, usually shows a leukopenia, the 
mononuclear leukocytes predominating. 

Paratyphoid Fever. — This infection occasions variable lesions in 
the intestines. There may be simple or follicular enteritis, or ulceration 
of the lymph-nodes has been seen. The systemic condition is more of a 
bacteremia without definite localizing manifestations. It is to be 
differentiated from typhoid by bacteriological tests. (See p. 308.) 



678 



A TEXT-BOOK OF PATHOLOGY 



Tuberculosis of the intestines may be primary or secondary. It 
may, in rare cases, occur primarily from the drinking of infected milk 
or consumption of the meat of tuberculous animals. Primary tuber- 
culosis of this character is most often seen in young infants. More 
commonly tuberculosis of the intestines is secondary to pulmonary or 
laryngeal tuberculosis, and is due to the swallowing of sputa. 

In following the course of the tubercle bacillus in its production of 
intestinal tuberculosis one must remember that this organism can 
pass the undamaged mucosa without leaving a trace. It may settle in 
a submucous lymphatic, or be carried to a mesenteric gland. In the 
former case the primary lesion is a submucous tubercle which can extend 
(a) along the transverse lymphatic vessels, (b) through the muscularis 
to a position under the serosa, and (c) toward the mesenteric insertion 
and to the mesenteric gland. If no lesions occur in the gut wall, but 
begin in the mesenteric glands, then the lesion may extend toward the 













i * 






• 













Fig. 313. — Tuberculous ulceration of the intestine. 



gut along the mesentery, and break out as subperitoneal tubercles 
which have the power to penetrate along the lymphatic vessels com- 
municating between the submucosa and peritoneum. Tuberculous 
peritonitis which usually assumes a plastic nature, may arise this way. 

The usual situation of the lesions is the lower end of the ileum, and 
it is the lymphoid tissues that are prone to be attacked. At first the 
follicles or Peyer's patches become enlarged and project above the sur- 
face. Soon they undergo necrosis and discharge their contents, leaving 
more or less irregular caseous ulcers. The follicular ulcers are small and 
rounded, but the more characteristic lesion is an irregular ulcer extend- 
ing transversely to the long axis of the bowel and often involving one-half 
or more of the entire circumference (Fig. 313). Generalized enteritis 
of catarrhal character may accompany the specific ulcerative disease. 

Microscopically, the changes are found to involve the mucous mem- 
brane and the adjacent submucous coat. Early caseation is charac- 
teristic. On the serous coat may often be seen granular elevations in 
clusters opposite the ulcers in the mucosa, and extending in lines from 



DISEASES OF THE GASTRO-INTESTINAL TRACT 679 

the region of ulceration round the bowel toward the mesentery (Fig. 
314). These represent tuberculous lymphangitis and small miliary 
tubercles in the course of the subserous lymphatic vessels. 

Tuberculous ulceration rarely causes perforation of the bowel, ex- 
cepting in the rectum, where periproctitis and fistula in ano may result. 
The ulcers may heal, causing cicatricial distortion or stenosis. Very 
commonly there is associated tuberculous enlargement of the mesenteric 
glands, and sometimes the latter are extensively diseased, though the 
primary intestinal involvement is insignificant. Occasionally there is 




Fig. 314. — Miliary tubercles in clusters and disseminated over the serosa (peritoneum) 
of the intestine; the clusters are situated opposite ulcerations of the mucous membrane 
(modified from Bollinger). 

found a very productive form of intestinal tuberculosis, usually of the 
ileocecal region, in which the mucosa hypertrophies even to the extent 
of being polypoid; the submucosa and muscularis become thickened, all 
layers showing caseous tubercles and tuberculous granulation tissue. 
In the human being this is at times associated with perienteritis so that 
a tumor-like mass may present itself. In the lower animals, especially 
birds, a continuous thickening of the whole tube appears with concentric 
narrowing of the lumen; the tumor-like form is seen, however. This has 
been ascribed to inflammatory or cicatricial stenosis of an infected stretch 
of gut wall and penetration of the process in all directions. It is inter- 
esting that ulcers do not occur in every case but the bacilli are numerous in 
the intestinal contents. 

There can be hematogenous miliary tuberculosis of the gut arising 
as a part of the general form, as peritoneal, subperitoneal, submucosal, 
or interstitial tubercles. 

Syphilis is most frequent in the rectum, though cases of syph- 
ilitic disease of the small intestine or colon, in the form of localized 
or diffuse gummatous involvement, sometimes with secondary ulcera- 
tion, have been observed, particularly in cases of congenital syphilis. 

The lesions take the form of pale infiltrations of the mucosa and sub- 
mucosa which may result in sluggish ulceration, lying crosswise of the 
axis and having a rather firm edge. 

In the rectum syphilis m&y appear in the form of warty elevations 



680 



A TEXT-BOOK OF PATHOLOGY 



or as a chancre; also as mucous patches, gummatous nodules, or infiltra- 
tions. Considerable thickening of the mucosa and submucosa, with 
ulceration and secondary cicatrization and stenosis (syphilitic stricture), 
may result. 

Anthrax occasionally affects the small intestine in persons exposed 
to infection by their occupations. It is met with among wool-sorters, 
brushmakers, tanners, and the like. More or less extensive ulceration 
is seen in the small intestine, and sometimes in the large intestine. The 
ulcers are dark colored and necrotic in appearance, and are commonly 
surrounded by a hemorrhagic zone. Considerable edema and hemor- 
rhagic infiltration of the neighboring parts of the intestine may ac- 
company the ulceration. The neighboring lymph-glands and the spleen 
are enlarged. The bacilli of anthrax are found in considerable numbers 
in the ulcers and in the surrounding tissues. 

Actinomycosis of the intestines is very rare. It most commonly 
affects the region of the cecum, causing first infiltrations, and then ulcera- 
tions of the mucosa and submucosa. 

Enteromycosis is a term applied to intestinal affections resulting 
from the ingestion of putrid meat, fish, sausages, and the like. Occa- 
sionally considerable epidemics may occur. The intestines may present 
the lesions of catarrhal enteritis or of intense croupous or pseudomem- 
branous inflammation, and there may be erosions or ulceration. Micro- 
organisms of various sorts have been discovered, but no specific form is 
recognized. The acute general symptoms, and even the local lesions 
may be caused by poisons elaborated by bacteria in tainted foods rather 
than by the micro-organisms themselves. 

TUMORS 

Connective=tissue Tumors.— Among the benign tumors of the 
intestines, fibroma, myoma, myxoma, and lipoma are occasionally met with 
in the submucosa as small nodular tumors or as pendulous polyps. They 
may occasion intestinal obstruction and even invagination. 

Sarcoma of the intestine is rare, but all varieties have been seen. Lymph- 
adenomatous enlargement of the solitary follicles or Peyer's patches 
may be met with in leukemia or pseudoleukemia. Lymphosarcoma is 
perhaps the commonest sarcoma of the gut wall and appears as diffuse 
thickening or as nodular masses arising from the lymphoid collections of 
the submucosa. It may cause dilatation by weakening the wall or tumor 
masses may narrow the lumen. Nodules of secondary sarcoma are not 
rarely met with in the mucosa and submucosa of the intestines (Fig. 315), 
and the serous covering may be studded with miliary nodules in sar- 
comatosis. 

Epithelial Tumors. — Among the epithelial tumors may be included 
inflammatory papilloma, adenoma, and carcinoma. 

Inflammatory hyperplasia of the mucous membrane may occur in 
association with chronic inflammations, especially in the large intes- 
tine, and may lead to the formation of papillomatous or polypoid eleva- 
tions of considerable magnitude. Structurally several varieties may be 
distinguished depending upon the fidelity with which they repeat the his- 
tology of the mucosa. This membrane seems to be able to continue its 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



681 




Fig. 316 — Adeno-carcinoma of intestines. To the right the normal mucosa, while in the 
middle and left parts, cancer nests are in the mucosa and submucosa. 



682 A TEXT-BOOK OF PATHOLOGY 

glandular grouping in papilloma, in some cases the result being merely 
many normal glands on a stalk of connective tissue, while in others an 
increase of glands and epithelial layers give the new growth an adenoma- 
tous character. 

Adenomata are more strictly of the nature of tumors, being independ- 
ent of inflammatory processes, although no sharp dividing-line can 
be drawn between the inflammatory proliferations and the adenomata 
proper. The latter may occur in the form of flat elevations having 
a more or less uneven surface and a tendency to hemorrhage and ulcera- 
tion; or in the form of papillomatous 
elevations of a cauliflower charac- 
ter. Adenomata arise by hyper- 
plasia of the crypts of Lieberkuhn 
in the duodenum, or of Muller's 
glands, and in their structure they 
present typical glandular acini, the 
tubules having a basement-mem- 
brane lined with cylindrical epi- 
thelium sometimes in more than 
a single row. They are at times 
combined with myomatous ele- 
ments, adenomyoma. Adenomata 
are most frequent in the rectum, 
but may occur in other parts of the 
large intestine and in the duodenum. 

Carcinoma is the most frequent 
tumor of the intestines. It occurs 
in the duodenum, especially at the 
papilla of the common bile-duct 
(Fig. 317); at the ileocecal valve, 
at the flexures of the colon, and in 
the upper or lower part of the 
rectum. The appearance is that 
of a soft, irregular, often ulcerated 
and bleeding elevation, projecting 
into the lumen of the gut and causing 
Fig. 317. — Carcinoma of papilla of Vater considerable narrowing, or sur- 
(Kast and Rumpel). rounding the bowel by circular 

involvement of the entire circum- 
ference. The carcinomata of the bowel are, for the most part, cylindrical 
epitheliomata (Fig. 318) or glandular cancers, consisting of atypical acini 
and tubules, with irregular proliferation and infiltration of the neigh- 
boring tissues with masses of epithelial cells. Cases are met with, 
especially in the rectum, in which there is a clear transition of adenoma 
into carcinoma (adenocarcinoma), and, in general, adenomata of the 
bowel have a tendency to such transformation (Fig. 319). At the lower 
end of the rectum squamous epithelioma may occur. 

There is a form of carcinoma of the intestine, perhaps most often seen 
in the appendix, appearing as small separate or grouped masses of gray 
or white submucous nodules. Histologically they show, in tubular and 




DISEASES OF THE G ASTRO-INTESTINAL TRACT 



683 



acinus arrangement, large pale epithelial cells with big nuclei and clear 
nucleoli. Such growths seem to exist a long time in some cases and are 
probably not actively malignant; perhaps because of this, cancers of the 




Fig. 319. — Adenocarcinoma of the rectum (adenoma destruens) (Karg and Schmorl"). 

appendix have the reputation of being rather benign; true malignant 
carcinoma of this organ does occur, however. 

The results of carcinoma of the bowel are the same as those of stenosis 
due to other causes, together with the consequence of the cancerous 



684 



A TEXT-BOOK OF PATHOLOGY 



cachexia and of metastasis. Ulceration of the tumor may lead to per- 
foration. Metastasis occurring to liver and other structures in the 
peritoneum is not uncommon. Outside of this cavity the secondary 
growths are rare. Secondary growths in the intestine are not so common. 
They come from growths in the stomach and uterus especially. Car- 
cinomata of the appendix are more common than previously supposed. 
They are of the scirrhous or simple variety and seldom cause symp- 
toms or metastases. 

Cysts may occur in the intestinal area from the remnants of fetal 
structures such as the blind end of a diverticulum one that has had, 
proximal and distal ends closed leaving a patulous and secreting mid-piece. 
Cysts of epithelial glandular origin are rare but prehaps more common 
in the lower animals than in man. 

PARASITES 

Vegetable Parasites. — Various forms of bacteria are found with 
such frequency in the intestinal contents that it is difficult to estimate 
their pathological significance. Tubercle bacilli, the bacillus of glanders 
and of typhoid fever, and the Streptothrix actinomyces produce the spe- 
cific lesions of these diseases. The Bacillus coli communis is a con- 
stant inhabitant, but probably assumes pathogenic properties and leads 
to inflammatory lesions when the conditions (such as irritation by coarse 
food, congestion, obstruction) favor its activity and multiplication. Un- 
der the same circumstances other micro-organisms likewise become active 
in the production of enteritis. The normal flora of the intestinal mucosa 
is pathogenic for the serosa when it reaches this layer by ulceration or 
perforation. 

Animal Parasites. — The animal parasites are discussed in detail 
elsewhere, but may be briefly mentioned here with reference to patho- 
logical results occasioned by their presence. Various forms of protozoa 
have been found, and may occasion inflammation when in considerable 
numbers. Coccidial psorospermia occur in the epithelium of the villi 
of the small intestine, and the Lamblia intestinalis may be found at- 
tached to the epithelium. The dysentery amebse may lie free in the 
contents, or may be found in the tissues, especially in the vicinity of 
ulcerations. They inhabit the large intestine, and are the cause of a 
certain kind of dysentery. 

The larger intestinal parasites are, for the most part, species of Vermes. 
Among the tapeworms, Tcenia saginata, T. solium, and Dibothriocephalus 
latus are the most frequent. Occasionally these may lead to intestinal 
obstruction by forming thick knots or coils, and sometimes the head of 
the worm may be attached in the mouth of the bile-duct, causing obstruc- 
tion and jaundice. Inflammatory changes are rarely met with as a result 
of these worms, although they may give off an absorbable poison of some 
toxic power. 

Among the nematodes, or round-worms, the Ascaris lumbricoides, 
or ordinary round-worm, is the most frequent. It is usually multiple, 
and may occasion obstruction of the intestine or inflammation. Some- 
times it perforates the intestinal wall, but it is improbable that the 
perforation is due entirely to the action of the worm. Previous intes- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



685 



tinal ulceration is the .more important condition. Obstruction of the 
bile-ducts or of the appendix may occasionally be due to lumbricoids. 
The Ankylostomum duodenale may cause petechial hemorrhages and in- 
flammatory disturbances in the duodenum or jejunum. The worms 
attach themselves firmly to the mucous surface by drawing a villus into 
their esophageal pouch. The Oxyuris vermicularis, or thread-worm, 
occupies the large bowel, multiplying in the cecum and descending in 
the mature state to the rectum; it may occasion considerable proctitis, 
and as mentioned before, has been held responsible for appendicitis. 
In female children vaginitis sometimes results from migration of the 
worms. The Trichinella spiralis when ingested in large numbers occasions 
violent gastro-enteritis, and its embryos perforate the wall of the intes- 
tine and migrate to the muscles. 

Larvae of various forms of flies occasionally occupy the intestinal 
tract, and owe their presence to the ingestion of the eggs with food. 
They may occasion enteritis, and may be found in immense numbers 
in the bowel or the stools. 

INTESTINAL RUPTURE AND FOREIGN BODIES 

Rupture may be due directly to traumatism or penetrating wounds; 
but more frequently results from ulcerations within. Duodenal (peptic) 
ulcers not infrequently perforate, and typhoid ulcers occasionally cause 
rupture. Tuberculous, dysenteric, and other ulcers are less prone to 
penetrate completely. The appendix may rupture from obstruction at 
its mouth and secondary catarrhal, necrotic, or gangrenous inflamma- 
tion of its walls. Rectal ulcers frequently cause painful diarrhea, proc- 
titis, periproctitis, and fistulse. 

Intestinal rupture usually leads to fatal peritonitis, but occasionally 
recovery ensues. A localized peritonitis, by walling off the infected 
area, may prevent general infection. The rupture may take place be- 
tween adherent coils, causing spontaneous intestinal anastomosis. 

Foreign Bodies. — Various bodies that have been swallowed may 
lodge in the intestines, pccasionally fecal concretions, enteroliths or 
coproliths, are found. These consist of a nucleus of epithelial cells, mucus, 
hair, and the like surrounded by inspissated fecal matter and earthy salts, 
particularly phosphate of lime and carbonate of calcium. They may 
cause considerable irritation, or even perforation, while in the appendix, 
where they are very frequently found, they are of importance in the de- 
gree that they obstruct the lumen and favor bacterial growths. 

Intestinal sand is a collection of fine particles of inorganic matter 
with a little oiganic matter. Certain foods, like bananas, favor its de- 
velopment. 

The Liver 

Anatomical Considerations. — The liver is peculiar in having a 
double circulation : one system of vessels, the portal vein and its ultimate 
subdivisions, receiving the blood from the digestive tract for functional 
purposes; the other system, the hepatic artery and its branches, supply- 
ing the nutritive blood for the walls of the blood-vessels and for the inter- 
lobular connective tissues, as well as to a certain extent the proper hepatic 



686 



A TEXT-BOOK OF PATHOLOGY 



structure itself. The portal capillaries ramify through the acini and 
empty into small branches of the hepatic vein lying in the center of the 
acini. The capillaries of the hepatic artery traverse the interlobular 
tissue and ultimately empty into the interlobular branches of the hepatic 
vein. The primary biliary capillaries are merely spaces between the 
hepatic cells, the larger formed capillaries occupying the interlobular 
tissues. While it is impracticable to discuss all the minute anatomy in 
a book like this, it is well to emphasize the large star-like endothelial cells 
of the liver capillaries (Kupffer's cells) which take a peculiar part in many 
lesions of the organ, and the small collections of lymphoid tissue be- 
tween the lobules which act at times like myelogenous elements. 

MALFORMATIONS AND CHANGES OF POSITION 

Congenital malformations are uncommon. There may be com- 
plete absence of the organ, especially in certain monstrosities; more fre- 
quently adventitious hepatic tissue is found in the suspensory ligament or 
elsewhere. Minor abnormalities in the lobes or fissures are more fre- 
quent. Absence of the gall-bladder and congenital stenosis or occlusion of 
the hepatic ducts are occasionally met with. 

Congenital Alterations of Position. — The liver may occupy the 
left side in transposition of the viscera. More rarely it is displaced 
downward or occupies other abnormal positions. 




Fig. 320. — Corset liver (from a specimen in the collection of Dr. Allen J. Smith). 



Acquired Changes of Form. — The most important of these is con- 
traction and lengthening of the organ by lacing. This gives rise to com- 
pression along the line of the lower margin of the ribs; the right lobe of 
the liver may thus be divided into an upper and a lower portion by a deep 
fissure. The capsule is frequently thickened and the superficial acini 
atrophic at the line of constriction (Fig. 320). Similar indentation by 
the ribs posteriorly, or by the right crus of the diaphragm, results from 
pulmonary affections and enlargements of the liver. Other changes of 
form, due to special diseases of the liver, will be discussed below. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



687 



Acquired Changes of Position. — Downward displacement may 
result from pleural effusion or emphysema; or it may be due to relaxa- 
tion and lengthening of the suspensory ligaments. The latter form is 
more common in women than in men, and is often part of a general 
visceroptosis. Tight lacing may be a cause of importance. Displace- 
ment to the right or left, or tilting upward of the lower edge, may occur 
in association with various abdominal and thoracic affections. 

CIRCULATORY DISTURBANCES 

Anemia of the liver may be part of a general anemia, or it may be 
due to pressure upon the organ, to various diseases of the liver substance, 
or to compression of the blood-vessels. The substance becomes pale and, 
if the anemia persists, undergoes 
degeneration. 

Active hyperemia is physio- 
logical during digestion, and occurs 
in association with various in- 
flammatory abdominal diseases. 
It is rarely extensive, and does 
not lead to marked pathological 
changes. 

Passive hyperemia results 
from obstruction to the circulation 
due to cardiac or pulmonary di- 
seases, to pleural or pericardial 
effusion or adhesions, or to throm- 
bosis or compression of the upper 
part of the inferior vena cava. It 
is especially characteristic of cardiac 
affections, the sluggish venous cir- 
culation of the liver accounting for 
the fact that this organ first evi- 
dences failing cardiac power. 

The liver increases in size, often 
considerably ; the edges are rounded, 
and the color on the surface is 
darker than normal. On section, 
there may be seen deeply congested 
central veins surrounded by lighter 
areas, representing the substance of the acini. If the process has per- 
sisted, secondary fatty degeneration of the peripheral zones of the acini 
or atrophy of these takes place, due to the pressure of the blood in the 
engorged capillaries and to the lower nutrition of the cells by the im- 
peded circulation, so that the light color of such portions, contrasting 
strongly with the dark, congested central vein, suggests the name nutmeg- 
liver (Fig. 321). In some instances of intense congestion small hemor- 
rhages may occur, especially in the portions lying beneath the capsule. 
In the later stages degeneration and reduction of size may take place 
and the organ may become dark red from deposit of hematogenous 
pigment. To this form the term red atrophy is sometimes given. In 




Fig. 321. — Nutmeg-liver: chronic congestion 
due to cardiac disease (Bollinger). 



688 



A TEXT-BOOK OF PATHOLOGY 



other instances hyperplasia of the connnective tissues between the 
lobules and acini occurs, while at the same time the organ is darkly 
pigmented and firm. The term cyanotic induration may appropriately 
be given to such. Cases of this sort are, in reality, instances of 
secondary cirrhosis. 

The outcome and sequels of the congestion will depend upon its de- 
gree and duration. In the severe cases of cardiac decompensation or in 
complete obstruction to the cava, degenerations will be more marked, 
while in long-standing moderate retardations of the venous return, con- 
nective tissue overgrowth will have time to occur and cyanotic indura- 
tion is therefore more common. In such cases one may see sometimes 
grossly, pale areas surrounding bile ducts in an arrangement suggesting 
racemose glands. These are evidences of regeneration and can be 
followed under the microscope as sprouts from the bile-ducts of large 
new liver cells at the margins of the lobules. 

Passive congestion of the liver may occasion considerable disturbance 
of the hepatic function. The most striking evidence of this is jaundice. 
This is probably due to the compression of the smaller biliary ducts and 
capillaries, and in part to swelling of the lining cells of these channels. 
The bile at the same time is probably thicker than normal, and does not, 
therefore, as readily escape through the ducts as in health. Microscopic- 
ally, one sees fatty degeneration of the liver-cells with pigmentation 
within and between them, and large liver-cells with large or reduplicated 
nuclei as evidences of attempt at repair. The capillaries are distended 
with blood, the liver columns separated, and probably hemorrhagic 
necroses about the central veins occur, although a chronic passive con- 
gestion may^'exist for some time without necroses. 

Embolism and thrombosis of the portal vein may occur in con- 
sequence of various diseases of the gastro-intestinal tract, particularly 
in cases of ulcerative enteritis. Embolic occlusion of one of the larger 
branches of the portal vein may occasion no serious circulatory dis- 
turbances on account of the free collateral circulation, and from the fact 
that the hepatic artery is capable of supplying the entire hepatic circula- 
tion. Embolic or thrombotic occlusion of the branches of the hepatic 
artery is similarly devoid of serious disturbance of the circulation , al- 
though a wedge-shaped hemorrhagic infarct, like a lung infarct, arises, 
but no degeneration is apt to follow unless the portal system for the same 
liver section is also damaged, in which case a hemorrhagic infarct appears 
which usually undergoes atrophy and secondary fibrous tissue over- 
growth then assuming the picture of an anemic infarct. 

Obstruction of the interlobular branches of the portal vein, and 
particularly when" several are coincidently occluded, may occasion 
decided nutritive disturbances in the hepatic acini. Small areas of 
necrosis having a grayish or yellowish and somewhat granular appear- 
ance, or in other cases foci of necrosis with hemorrhagic infiltration, are 
the striking lesions. Such conditions are observed in most instances of 
death from puerperal eclampsia in consequence of toxemic thrombosis 
or of embolism of placental cells (Fig. 322), and in consequence of various 
intoxications or infections having their origin in the distribution of the 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



689 



portal circulation. The immediate cause of the lesions in the latter 
condition is hyaline thrombosis of the interlobular portal vessels. 

Thrombosis of the portal vein is most frequently the result of infec- 
tive inflammation of the vein (pylephlebitis), resulting from ulcerative 
enteritis, appendicitis, or similar processes involving the parts from which 
the portal blood is received. There may be a gradual ascending inflam- 
mation and thrombosis extending from the primary focus of disease to 




Fig. 322. — Coagulation necrosis of the hepatic cells in a case of puerperal eclampsia (Karg 

and Schmorl). 

the portal vein; or the latter may be involved in a more direct manner by 
infectious embolism. The portal vein and its branches in the liver become 
more or less obstructed, and large abscesses appear in the course of the 
main trunk or, if the emboli be small and numerous, multiple small ones 
are scattered along the finer branches. At the same time the obstruc- 
tion of the vein occasions intense passive hyperemia of the peritoneum, and 
ascites results. 

ATROPHY AND DEGENERATIONS 

Atrophy of the liver occurs in cases of death from senility, inani- 
tion, or from various organic diseases. (Pressure-atrophy has been re- 
ferred to above. Acute yellow atrophy is described below.) 

The greater part of the liver structure may be affected, or the atrophy 
may be confined to the edges or other limited portions. The liver is 
more or less uneven, and may at the same time be somewhat pigmented* 
Microscopically, the liver-cells are decreased in size^ granular, and dark 
colored. At times the acini may disappear entirely, and reactive hyper- 
plasia of the stroma and even proliferation of biliary ducts may ensue. 

Localized atrophy occurs in the vicinity of tumors, in the acini sur- 
rounded by hyperplastic connective tissue in cirrhosis, and in parts of 
the liver otherwise subjected to pressure. The liver-cells of the affected 
part become distorted and decreased in size, and are deeply pigmented. 
In the later stages they break down completely and are removed. Red 
atrophy (see Congestion of the Liver) is a form of pressure-atrophy with 
pigmentation, the compression of the hepatic cells being due to over- 
distention of the hepatic veins and capillaries. 

44 



690 



A TEXT-BOOK OF PATHOLOGY 



Pigmentation of the liver is prone to occur on account of the slug- 
gish circulation through that organ, and may be of various kinds : 

1. Hematogenous pigmentation (hemachromatosis) in the portal 
areas. Particles of altered blood-pigment are often deposited in the 
interlobular tissues, especially in Kupff er's stellate cells, or in the periph- 
eral zones of the acini in cases of abnormal blood obstruction in the portal 
circulation. This is particularly common in pernicious anemia. In this 
disease the peripheral zones of the acini are habitually infiltrated with 
pigment matter, which responds to tests for iron, such as with ammonium 
sulphid or ferrocyanid of potassium and hydrochloric acid. Somewhat 
similar pigmentation of the liver may occur in cases of absorption of hemor- 
rhagic effusions in the peritoneum, or in consequence of other forms of 
blood destruction. Analogous pigmentation is often met with in the 
livers and other abdominal organs of drunkards. In the slate-colored 
liver of chronic malaria pigment is found along sinusoids, especially in 
Kupffer's cells. This is thought to come from the destroyed plasmodia 
and from disintegrated red blood-cells. 




Fig. 323. — Fatty infiltration of the liver. 



2. Hematogenous pigmentation of the central portions of the acini 
has been noted in connection with a red atrophy of the liver consequent 
upon congestion. 

3. Biliary pigmentation results from obstruction of the biliary ducts, 
and is constantly met with in certain forms of cirrhosis and in the vicinity 
of new growths which compress the biliary passages. In jaundice, bile- 
pigments are found within liver-cells and in the supporting tissue. 

4. Very rarely anthracotic pigmentation has been observed. In 
one case, at least, there was associated cirrhosis. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



691 



Fatty infiltration is more or less physiological, especially in children 
and in overfed individuals. Pathologically, there may be diffuse in- 
filtration or deposit in the liver-cells of all parts of the organ. Such 
pathological fatty liver may result from overeating and general obesity, 
or may be due to pulmonary disease or anemic and cachectic conditions. 
It has generally been held that the immediate cause is retarded oxidation, 
in consequence of which fat accumulates. It is probable, however, that 
there is some disease of the hepatic cells, rendering them more active in 
storing, or less active in disposing of, fats. This seems especially true 
in certain cases due to poisons which cause a deposit of fat in the liver, as 
in geese pampered by antimonial poisoning. 

The liver increases in size, often considerably; its edges are rounded, 
its consistency is doughy, and the color is rather yellowish and glistening. 
On section, there may be visible exudation of oil-drops and the knife 
may be covered with droplets. 

Microscopically, the process is found to begin in the peripheral 
portions of the acini in the form of droplets within the hepatic cells. 
Soon these increase in size by confluence, adjacent cells are involved, 
and the entire acinus eventually becomes affected (Fig. 323). In ex- 
treme cases the hepatic cell is filled with a single large oil-drop, which 
compresses the protoplasm and nucleus. The blood-vessels and other 
structures may be completely hidden from view, and the pressure of the 
fatty deposit may be sufficient to pioduce a certain degree of anemia, 
though not enough to occasion serious circulatory disturbances. The 
functional activity of the liver is diminished. 

Parenchymatous degeneration, or cloudy swelling, occurs in va- 
rious infectious fevers and in consequence of intoxications, notably by 
phosphorus, arsenic, and antimony. The liver is somewhat enlarged, and 
of an opaque, grayish-yellow appearance, the outlines of the lobules being 
extinguished. Microscopically, the liver-cells are found filled with fine 
albuminous granules more or less obscuring the nucleus. In most in- 
stances cloudy swelling terminates by return to the normal state ; but if 
the intoxication or infection is continued, fatty degeneration may result. 

Fatty degeneration may occur as the result of severe anemia, par- 
ticularly pernicious anemia, or following cloudy swelling, as the result 
of infectious diseases or of intoxications. Among the infections, pyemia, 
yellow fever, relapsing fever, and erysipelas are notable examples. 
The liver may be greatly decreased in size and softer than normal; the 
substance not rarely is friable. The color is yellowish and oil-drops 
may exude from the surface. Microscopically, the hepatic cells are 
filled with small granular particles or droplets of fat, and in the advanced 
stages they break down completely into granular detritus. The nucleus 
is not pushed aside, but may show fragmentation of the chromatin. 
The liver-cells may contain single large drops of fat practically indis- 
tinguishable from those seen in fatty infiltration. The distinction of the 
two conditions may be exceedingly difficult. Fatty degeneration of local- 
ized areas of the liver or of individual acini or cells occurs in association 
with chronic hepatitis or other diseases causing pressure upon the acini. 

Acute Yellow Atrophy. — The most advanced fatty degeneration 
of the liver occurs in the affection of the organ termed acute yellow atrophy. 



692 



A TEXT-BOOK OF PATHOLOGY 



This condition is most frequent in young women, and especially in those 
addicted to the excessive use of alcohol. Occasionally syphilis seems the 
etiological factor, and in acute phosphorus- and late chloroform-poisoning 
the appearance of the liver is similar to that which is recognized as acute 




Fig. 324. — Acute yellow atrophy of the liver, showing extensive fatty degeneration and in 
places complete destruction of the liver-cells (Kast and Rumpel). 

yellow atrophy. Finally, some cases are idiopathic, arising without recog- 
nizable cause, which are now attributed to autogenous poisons from the 
intestinal or genital tract. Parturition seems a determining cause in 
some cases. Micro-organisms of various kinds have been found, and it 
is likely that all cases are toxic or infectious. 




Fig. 325, — Acute yellow atrophy of the liver from a case occurring during pregnancy. 

The exact cause and its operation are not known but there are rea- 
sons to indicate that even for the idiopathic form it may not be single. 
Formerly it was considered that the form following phosphorus poisoning 
and the acute toxic variety were the same, but later observations 
indicate that the poisonous metal destroys fat oxidizing ferments with 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



693 



the accumulation of fat in the parenchyma, leaving the nucleus intact, in 
the cells lying at the periphery of the lobule, whereas in idiopathic acute 
atrophy the whole cell, including the nucleus, maybe every unit in an 
entire lobule, goes to pieces. Moreover in the former variety there are 
evidences of regeneration. The poison of the primary variety seems to 
have a special predilection for the liver parenchyma while phosphorus 
attacks as well the heart and kidney. Arguing upon these and other 
data, Wells believes that acute toxic yellow atrophy is due to a poison 
which destroys the specific function of the liver-cells without inhibiting 
their autolytic enzymes and that the symptoms are due to failure of 
liver functions because so many secreting elements are dissolved. 

Pathological Anatomy.- — The liver is probably at first larger than 
normal but very soon becomes decreased in size and remarkably soft and 
friable, the capsule being wrinkled. On section, there is found a varie- 
gated appearance, the prevailing color being a brownish or grayish yellow, 
in which are scattered bright or dark red areas. The yellowish areas 
represent the degenerated and pigmented hepatic cells ; the reddish areas, 
foci of hemorrhagic infiltration or pigmentation, or, if seen late in the 
condition, places where regeneration is beginning. When the hemor- 
rhagic manifestations dominate the field the term "red atrophy" is 
given. The process usually begins in the left lobe, but rapidly involves 
the entire organ. 

Microscopically, the hepatic cells are found to have undergone rapid 
fatty degeneration or necrosis, and are filled with or replaced by yellowish 
pigment particles. In the idiopathic variety, the cell remains in the yellow 
areas as a shadowy outline enclosing fat globules, while in the red areas 
hemorrhage pigmentation and coagulation may remove all vestige of cell 
wall. In the metallic poisonings the cell architecture is more apt to be 
recognizable. There are however, cases in which the differences mentioned 
here and in the preceding discussion are by no means discoverable; 
gradations of all kinds appear. In the liver of pregnancy the periportal 
areas show the greatest fatty change. ; As the case proceeds, round and 
connective tissue cells appear in the field and the bile ducts take up their 
function of replacing liver-cells by attempts at regeneration. Since the 
disease is usually fatal no restitution of the liver appears. However, 
it would seem that small areas of this kind of necrosis do occur, in preg- 
nancy and certain intoxications, from which recovery ensues. In these 
cases, liver-cell regeneration occurs in a somewhat atypical manner amid 
irregular new connective tissue. v . 

Associated Conditions. — Acute yellow atrophy leads to intense 
cholemia, in consequence of which biliary pigmentation of the various 
structures of the body may develop. Petechial hemorrhages may occur 
in the mucous or serous membranes or in the skin. The urine contains 
leucin and tyrosin. More or less profound acid intoxication may occur. 
(See Acid Intoxication, Part I.) ' 

Amyloid infiltration occurs in consequence of syphilis, tuberculosis, 
and suppurative diseases of the bones, or as a result of long standing 
cachexia. It is habitually associated with amyloid disease of the spleen, 
and often of the kidneys and other structures. 

Amyloid infiltration begins in the smallest blood-vessels between 



694 



A TEXT-BOOK OF PATHOLOGY 



and within the acini, causing a more or less pronounced thickening of 
their walls. The liver-cells themselves may be secondarily involved, 
but more frequently undergo atrophy and fatty degeneration in con- 
sequence of the pressure and of diminished nutrition due to compression 
of the blood-vessels (Fig. 326). 

The liver is enlarged, denser than normal, its edges rounded, and 
the tightly drawn capsule is smooth and glistening. Not rarely it 
presents a striking translucency, and on section the color is grayish 
white or yellow. The peripheral and central zones of the acini are 
sometimes readily distinguished by their light color from the inner- 
most portions, which are least affected. 




Fig. 326. — Amyloid liver (from a photograph by Dr. Wm. M. Gray). 

Dropsical infiltration of the liver-cells occurs in cases of intense 
infection and intoxication, especially such as originate in some part of 
the portal circulation. It is found particularly in the vicinity of necrotic 
areas due to embolic occlusion of the interlobular portal veins. The 
liver substance is swollen, and, microscopically, the cells are cloudy and 
ofttimes vacuolated. The cells and columns are pushed apart by the 
fluid. 

Necroses of the liver occur as large areas or in small foci. They 
are found in infections and intoxications, the former causing focal, 
the latter massive, lesions. The pathological alteration is coagulative. 
The focal necroses of typhoid fever, septicemia, and the like are small 
opaque, yellowish-gray, ill-outlined dots in the parenchyma, giving the 
microscopical appearance as outlined under Necrosis (q. v.). 

INFLAMMATIONS 

Hepatitis, or inflammation of the liver, may be of several forms: a 
parenchymatous, an acute interstitial, or a chronic interstitial. 

Parenchymatous Hepatitis. — In the course of various infections 
and intoxications a certain amount of parenchymatous degeneration 
of the liver-cells may take place. This was formerly described under 
the name " parenchymatous hepatitis.'' The term is generally in- 
appropriate, though in some instances there is associated with the 
degeneration of the hepatic cells a certain amount of cellular infiltration 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



695 



and reactive inflammation. To such cases the term " parenchymatous 
inflammation " might be applied, though, in reality, even these are more 
degenerative than inflammatory in nature. To the combination the 
term " acute diffuse hepatitis'' may be applied. The lesion is com- 
moner in the general infections of the lower animals than in man. It 
is sometimes impossible to say which structure, parenchyma or its 
support, is affected most. 

Acute Interstitial Hepatitis and Abscess of the Liver. — Bac- 
teria may gain access in several ways. In some cases penetrating 
wounds, or perforation of gastric or duodenal ulcers or of other patho- 
logical lesions into the liver, occasion direct infection. In other cases 
the micro-organisms are carried in the circulation and enter the liver 
with the portal or hepatic blood, or by retrograde embolism through the 
hepatic veins from the vena cava. Finally, infection may occur by 
invasion of the bacteria along the bile-ducts. 

Most frequently hepatic abscess is secondary to ulcerative disease 
of the intestines, notably dysentery. In this disease the specific ameba? 
are carried to the liver in the portal circulation, and occasion necrotic 
foci in which the bacteria carried with the amebse multiply and give 
rise to the further changes constituting an abscess. Similar embolic 
abscesses occasionally follow appendicitis and perityphlitis, or various 
forms of intestinal ulceration. Thrombophlebitis of the portal vein 
not rarely extends to the smaller branches within the liver, and occa- 
sions multiple suppurative foci. 

In cases of general pyemia multiple abscesses of the liver may occur, 
especially when the primary infection occurs within the abdomen. 
Infection by invasion along the biliary tract is especially prone to occur 
when there is obstruction of the bile-ducts by calculi or otherwise. In 
tropical countries traumatism without visible contusion may lead to 
abscesses, and it is not unlikely that micro-organisms from the biliary 
passages penetrate the hepatic structure in the injured portions. 

Among the micro-organisms that have been discovered are the 
streptococci and staphylococci, the Bacillus coli communis, and others 
less frequently. 

Pathological Anatomy. — Dysenteric and traumatic abscesses are 
usually solitary, and generally occupy the right lobe. In the early stages 
they appear as spots of grayish or yellowish color, in which the division 
of the lobules is lost and which assume a more and more granular ap- 
pearance. Subsequently softening takes place and a cavity is formed. 
This increases in size until, in advanced cases, it may reach enormous 
proportions. The contents consist of curdy or creamy, or at times thin, 
pus having a yellowish, brownish, or often quite reddish appearance 
depending upon the proportion of blood and bile, and the wall is composed 
of an ill-formed pyogenic membrane. The abscess may consist of a 
single cavity or may be partially lobulated. Sometimes there are 
multiple abscesses. If the cavity is small, resorption of the pus may 
take place and a cicatrix may result. In other cases inspissation and 
encapsulation ensue. If the lesion be near the surface or progress 
to it as enlargement occurs, a plastic peritonitis usually appears over 
the liver at this place. Should time and sluggishness of the inflammation 



696 



A TEXT-BOOK OF PATHOLOGY 



permit, productive and limiting adhesions may form but in rapid sup- 
puration or with large abscesses, rupture may occur into the pleura, 
into the stomach or intestines, into the peritoneal cavity, or externally. 
Not rarely the diaphragm and lungs are penetrated, and the pus is evacu- 
ated through the bronchi. 

When suppuration is consequent upon pylephlebitis or cholangitis, 
small grayish yellow areas are first noted along the distribution of the 
respective systems, although abscesses may begin at the hilus of the liver 
in the portal vein or bile-duct and continue as infiltrations irregularly 
through the tissue. There tends to be some regularity or system 
of distribution in these cases however, a character lacking in the irregu- 
larly disseminated abscesses sewn by arterial embolism. 




Fig. 327.^ — Liver of chronic passive congestion in stage of red atrophy with beginning 

connective tissue increase. 

Chronic Interstitial Hepatitis or Cirrhosis of the Liver. — These 
terms are applied to a group of affections characterized by more or less 
diffuse hyperplasia of the connective tissue of the liver, usually most 
pronounced in the interlobular tissues and surrounding the branches 
of the portal vein, but sometimes invading the lobules themselves. 
Atrophy or fatty change or, less commonly, certain atypical forms of 
hyperplasia of the liver-cells precede or accompany the connective- 
tissue hyperplasia.' In some instances the capsule of the liver is also 
involved in the fibrous overgrowth. 

The etiology of cirrhosis is still in many respects obscure. The irri- 
tants, toxic agents or bacteria, may reach the liver through the portal 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



697 



vein, the hepatic artery, the biliary channels, and possibly via the lym- 
phatics or the peritoneal covering of the organ. The most important 
routes are the portal vein and the bile-ducts, as either of these 
furnishes a possible path for the entrance of the many forms of micro- 
organisms that may occupy the intestinal tract; the portal vein in par- 
ticular may convey poisons ingested or manufactured in the stomach 
or intestines. It has been thought by some observers that disturbed 
splenic function, especially when associated with hemolytic pigmentation, 
stands in an obscure etiological relationship to cirrhosis. It is stated 
that enlargement of the spleen sometimes precedes clinically discoverable 
changes in the liver and that splenectomy retards or obviates the lesion. 
The occurrence of cirrhosis following certain general infections (scarlatina, 
malaria, syphilis) suggests the possibility that the causative agents 
may enter through the hepatic artery — -that is, from the systemic arterial 
blood. It seems accepted in many quarters that the processes usually 
classified as strict cirrhosis are reparative connective tissue hyperplasias 
in response to destruction of parenchyma. While this may indeed be 
the proper explanation, those cirrhoses called biliary are usually accom- 
panied by rather active cellular infiltrations along the bile channels 
and may in the obstructive form be really interstitial inflammations. 
In the portal form parenchymatous degenerations seem to precede 
fibrous tissue growth. 

A form of hepatic fibrosis that, pathologically speaking, may be 
regarded as chronic interstitial hepatitis is that which follows long- 
standing congestion of the liver in cases of cardiac disease, emphysema 
of the lungs, and other causes of stasis in the inferior vena cava. The 
terms cirrhosis from passive congestion and cardiac cirrhosis are some- 
times used. In this condition the central veins of the lobules are over- 
distended, and pressure-necrosis of the surrounding liver-cells followed 
by endothelial hyperplasia and intralobular fibrosis are later develop- 
ments. The cross-section of the liver shows a variegated appearance, 
due to the dark (congested) central zone of the lobules and the lighter 
colored periphery. The term nutmeg-liver indicates this stage. Finally, 
the fibrosis becomes more extensive, and the whole organ is more or 
less deeply stained with blood-pigment (red atrophy or induration) . 

Localized areas of fibrosis may occur in the liver, as in any organ 
around tumors, granulomatous processes, or any pathological area. 

Varieties of Cirrhosis. — Two types of cirrhosis, sufficiently dis- 
tinctive in their pathological and clinical features to be regarded as 
separate entities, are the portal and the biliary. The older terms, 
atrophic and hypertrophic, are falling into disuse as less distinctive. A 
portal cirrhosis may be atrophic or hypertrophic, and a biliary cirrhosis 
is not of necessity hypertrophic. 

Portal Cirrhosis. — Gin-drinker's liver, Laennec's cirrhosis, is an inter- 
lobular increase of connective tissue causing compression of lobules and 
portal radicles (Fig. 328). It is the commonest form of cirrhosis of the 
liver, and has been ascribed to excessive use of spirits, especially raw. 
There seems to be small doubt that sedentary life, gastro-intestinal 
disorders, and alcohol predispose to this form, an opinion not at all 
inconsistent with the present idea of its immediate causation. It is 



\ 



698 



A TEXT-BOOK OF PATHOLOGY 



generally ascribed today to toxic agents passing in through the portal 
vein, causing necrosis of the adjacent liver-cells, a round-cell infiltration 
about the radicles of the portal vein, fatty metamorphosis, connective- 
tissue overgrowth, and secondary contraction. This affects the nutri- 
tion of the liver parenchyma, favors continuance of degeneration, and 
so squeezes the softer tissue that a roughening of the surface results 
(hob-nail liver). 

It has been suggested that the colon bacillus may be a factor in 
the causation of portal cirrhosis, since it will induce fibrosis when gain- 
ing access to a liver already the seat of necrosis or fatty change, a theory 
fairly well supported by experimental evidence. Chronic gastrointes- 
tinal disease, often a forerunner of cirrhosis, gives ample opportunity 



for focal or diffuse loss of resistance in the liver, because considerable 
amounts of toxic substances are formed and so pass through this organ 
in the portal circulation. Longcope has shown experimentally that 
repeated intoxications by protein may cause parenchymatous degeneration 
and connective-tissue overgrowth; this is in line with the foregoing since 
it matters not whether the protein be animal or bacterial . The constant 
use of alcohol, a habit undoubtedly favoring cirrhosis, supplies an 
easily oxidizable substance to the liver, and food fat, not so easily burned, 
is stored, thus acting as a great burden for the cell, so that bacterial 
infection is met with no resistance, the cell succumbs, and fibrosis follows 
(Fig. 329) . The older idea that alcohol acts as a direct irritant to the 
hepatic cells and by destroying these initiates the cirrhotic process can- 
not as yet be thrown aside. 

Morbid Anatomy. — In the earliest stages the liver is often enlarged, 
but in the typical advanced form it is contracted, extremely hard, 
granular or irregularly uneven on the surface, and, on section, resistant 




Fig. 328. — Atrophic cirrhosis of the liver (Laennec type). 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



699 



to the knife. The size of the liver, even in advanced stages, is by no 
means always small. A study of statistics obtained at the postmortem 
table shows that the liver in perhaps a majority of the cases of other- 
wise typical Laennec's cirrhosis is larger than the normal organ. This 
is due to fatty infiltration of the liver-cells, to associated congestion, 
or to an attempt at replacement of lost parenchyma by hypertrophy or 
hyperplasia. This attempt is transient and ineffectual. The highly 
fatty cirrhosis of the interlobular type gives a liver of egg-yolk color. 
The surface of section presents bands of connective tissue surrounding 
groups of acini, and compressing them so that they rise above the sur- 
face. The connective-tissue bands are dull gray or white in appear- 
ance, the enclosed acini yellowish or brownish. 




Fig. 329. — Fatty alcoholic cirrhosis. 



The growth of connective tissue follows its usual course of excess, 
and is shortly found as wide, irregular bands, rather poor in cells, sepa- 
rating the lobules ("unilobular"). It may instead embrace a group 
of lobules, giving rise to the so-called " multilobular cirrhosis." 

Microscopically, cirrhosis is characterized by a proliferation of the 
connective tissues around the interlobular branches of the portal vein. 
In the earlier stage this occurs in the form of round-cell infiltration 
and proliferation of fibroblastic cells, causing moderate obstruction to 
the portal circulation. Later, the connective tissue becomes sclerotic, 
greater compression of the portal veins ensues, and considerable ob- 
struction of the circulation results. At the same time the acini are 
compressed and suffer degeneratioD and atrophy. The atrophic lobules, 
with their degenerated and pigmented liver-cells, may be a striking fea- 
ture in the histological picture. There is little tendency to extensive 
invasion of the acini themselves by the inflammatory process. New- 



700 



A TEXT-BOOK OF PATHOLOGY 



formed biliary ducts may be present in considerable numbers in the 
hyperplastic interlobular tissue and some of them may be seen running 
into the lobules. When they enter, the lining cells become large, 
pale, and have an abundantly chromatic nucleus. This is an attempt 
to regenerate parenchyma; such an attempt may at times be made by 
the old liver cells but is usually ineffectual. 




Fig. 330. — Advanced grade of Laennec's cirrhosis. 



Associated Changes. — 'The marked result of atrophic cirrhosis is 
obstruction to the portal circulation. This occasions congestion of the 
spleen and gastro-intestinal mucosa and, eventually, ascites; the venous 
obstruction is seen in hemorrhoids, varices at the cardiac end of the 
stomach and in the mesenteric veins. When the obstruction becomes 




Fig. 331. — Varices of esophagus in cirrhosis of liver (from the Vienna General Hospital 

Collection). 

extreme, collateral circulation may relieve the congestion of the portal 
system. The most prominent anastomoses are those between the 
gastric and esophageal veins, and between the hemorrhoidal veins 
and the veins of Retzius with the retroperitoneal veins. The veins of 
the round ligament increase in size and may communicate with the 
superficial veins at the umbilicus (caput medusae) . 



DISEASES OF THE GASTRO-INTESTINAL TRACT 



701 



Gastro-intestinal catarrh and enlargement of the spleen are usually 
prominent in cirrhosis. Jaundice is rare, because the bile-ducts are rarely 
compressed. There may be a low-grade cirrhosis of the pancreas. 

In some instances the liver is large and smoother, softer and lighter 
in color, from the fact that considerable fatty infiltration of the acini is 
associated with the cirrhosis (fatty cirrhosis, Fig. 329), This is the so- 
called " beer-drinker's liver." In one case, in a small man seen by one 
of the authors, the organ weighed 9}^ pounds. In the later stages 
such cases may become converted into the typical form by absorption 
of the fat. 

Pathological Physiology. — 'Cirrhosis of the liver occasions gastro- 
intestinal symptoms by obstructing the portal circulation, and prob- 
ably also by altering the functional action of the liver. Metabolic 
disorders of some sort also result from the hepatic disease, but the nature 
of these is as yet unknown. There is often a toxic state with delirium, 
the exact cause of which is not understood. The fatal termination 
often comes in the form of sudden or gradual coma, which is probably 
toxemic. 




Fig. 332. — Biliary cirrhosis of liver. 



Biliary cirrhosis is a form accompanied by inflammatory, obstruc- 
tive, and pigmentary changes in or surrounding the bile-duct system. 
Any one of these may dominate the pathological picture (Fig. 332). 

Two types have been described: In the first, obstructive biliary cir- 
rhosis, the hepatic disease follows obstructions of the biliary ducts, 
and is, therefore, largely of mechanical origin; in the second, HanoVs 
hypertrophic cirrhosis or true biliary cirrhosis, gross obstruction of the 



702 



A TEXT-BOOK OF PATHOLOGY 



ducts does not precede the hepatic lesion. At most,, catarrhal chol- 
angitis precedes or accompanies the disease and may in part occasion 
the associated jaundice. 

Obstructive biliary cirrhosis is a fibrous overgrowth due to back 
pressure upon bile channels, which causes stagnation, peribiliary con- 
gestion, liberation of irritative pigment, reactive tissue change, and 
fibrosis. The obstruction may be due to gall-stones, tumors, or atresia 
of the bile-ducts. 

The appearance of the liver is much the same as that seen in hy- 
pertrophic cirrhosis of the Hanot type. The organ is uniformly en- 
larged, and may be somewhat granular upon the surface or entirely 
smooth. On section, the substance is found to be deeply bile stained, 
and has a yellowish or greenish color. The substance is firm, and the 
overgrowth of connective tissue may be visible on the surface. Bile- 
ducts, distended and irregular, are to be seen. 

Microscopically, the first discoverable changes are areas of insular 
necrosis in the peripheral, zones of the acini. Subsequently, prolifera- 
tion of connective tissue replaces these and spreads to the interlobular 
tissues. Proliferation around the interlobular biliary capillaries (peri- 
angiocholitis) may be a striking characteristic from the first, and multi- 
plication of new bile-ducts and of hepatic cells is observed. In cases of 
absolute obstruction of the gall-ducts, and in cases in which active 
chemical changes in the bile have occurred, rapid fatty degeneration 
and acute atrophy of the liver may be the terminal phases. The spleen 
is little, if at all, enlarged, and ascites does not occur until very late, if at 
all.- 

Hanot' s cirrhosis is a diffuse increase in fibrous tissue following 
the bile-ducts and associated with inflammatory changes in and around 
them. The cause is generally thought to be an infection traveling up 
the biliary system. By reason of the association of bile-ducts in the 
interlobular septa with the intralobular bile radicles, the infiltrative and 
proliferative processes invade the outer sections of the lobules and do 
not remain so largely interlobular as is the case in Laennec's cirrhosis. 

Microscopically, proliferation in the interlobular connective tissues 
is found, as in the atrophic form, but it does not bear the same relation 
to the portal veins and is less prone to cicatricial contraction. Unlike 
the portal form, there is decided extension into the peripheral zones 
of the acini, and everywhere between the columns of hepatic cells there 
may be seen proliferated fibroblastic cells. This inward extension of the 
fibrous tissue separates and distorts segments of bile radicles and small 
ducts near the lobular border, giving the appearance of many newly 
formed bile-ducts. There is, indeed, an actual increase of bile-ducts. 
Their prominence on section seems due to an attempt at regeneration 
by peripheral parenchyma cells. All these changes are accompanied 
by biliary pigmentation, manifested both in the organ and generally in 
the body. There is no obstruction to the portal or gastric circulation, so 
that ascites and varices do not occur. The spleen is always enlarged 
and sometimes decidedly so. 

Pigmentary Cirrhosis. — Certain rare forms have been ascribed to 
carbon, but the most important is that associated with hemosiderosis. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



703 



due probably to excessive blood destruction, and associated with the 
bronzed diabetes of chronic pancreatitis. Again, in Banti's disease, with 
its excessive hemolysis, probably due to increased splenic activity, 
there is a pigment collection in the liver which may lead, in the advanced 
stages, to a cirrhosis. In long standing malaria, an atypical cirrhosis 
may occur. All these just mentioned forms are more irregular in type 
then the two essential cirrhoses. 

Large scars may occur after massive destruction of liver tissue, 
in acute yellow atrophy, poisoning, gummata, etc. These have been 
called " toxic cirrhoses, ' but it is well to remember that they represent 
finished reparative processes, and do not tend to spread. Of this nature 
may be the fibrosis in the vicinity 
of tuber culomata, which some 
authors have called " tuberculous 
cirrhosis." 

Perihepatitis. — Inflammation 
of the capsule of the liver and of 
the superficial portions of the 
hepatic structure may be associated 
with cirrhosis (Fig. 333), and not 
rarely occurs in consequence of 
chronic peritonitis. It may lead 
to considerable thickening of the 
capsule. The pressure of the con- 
tracting fibrous tissue may occasion 
atrophy of the underlying hepatic 
substance, and a more or less un- 
even and atrophic organ results. 
Primary inflammation of the cap- 
sule may be an expression of 

syphilitic infection, and may occur alone or in association with thickening 
of the peritoneum. Reference will be made, in the discussion of diseases 
of the peritoneum, to a special form of hyperplastic perihepatitis — that 
known as the Zuckergussleber of Curschmann. 

Acute perihepatitis is usually a part of general peritonitis but may 
result from the extension of abscesses in the organ or by penetration of a 
pleuritis through the diaphragm. 

Syphilitic cirrhosis is to be mentioned because of its common occur- 
rence in congenital syphilis. The liver is large and hard, and the fibrosis 
is pericellular, separating not only liver columns, but the cells them- 
selves. Gummata are usually present. Spirochetes are exceedingly 
numerous. 




Fig. 333. 



—Perihepatitis associated 
cirrhosis of the liver. 



with 



HYPERTROPHY 

The regeneration after injuries of the liver shows the power of the 
liver-cells to undergo active multiplication. Not rarely, active hyper- 
plasia of liver-cells, from liver-cell or bile-duct epithelium, throughout 
the entire organ may occur in association with other diseases, notably 
hypertrophic cirrhosis. A simple hypertrophy of the liver also occurs 
in certain well-developed, robust individuals. Enlargements of the 



704 



A TEXT-BOOK OF PATHOLOGY 



liver formerly regarded as hypertrophies are, for the most part, due to 
pathological conditions. Enlargements of one of the main lobes after 
destruction of large parts of the other have been observed. 

Regeneration of healthy liver can take place when a portion has been 
destroyed by injury. The hypertrophic and hyperplastic cells in this 
case and in cirrhosis are large, sharply outlined, and take the stain more 
deeply. Bile-duct epithelium seems to be able to generate liver-cells. 

RUPTURE OF THE LIVER 

Rupture may occur from direct traumatic injury, and is particu- 
larly common in the newborn when forcible delivery has been neces- 
sary. In the latter cases small injuries with secondary hemorrhagic 
infiltration are observed near the surface of the organ. Portions of 
liver-cells may be loosened and may be carried as emboli to the lungs. 
The injury is repaired by active hyperplasia of the liver-cells and of the 
biliary capillaries, and in this manner the affected part may be restored 
without the development of scar tissue. Large injuries, however, occa- 
sion the formation of cicatiicial tissue. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of minute, translucent, miliary 
tubercles, which may be scarcely visible to the naked eye (Fig. 334), 

or in the form of larger foci. Tuber- 
culosis of the liver is always a sec- 
ondary disease. The tubercles arise 
in the interlobular tissue or in the 
acini themselves. The larger caseous 
tubercles are rare; they may be asso- 
ciated with a local or diffuse sclerotic 
contraction of the organ. The as- 
sociation of general cirrhosis and a 
tuberculous lesion is frequent, but 
probably accidental. In the im- 
mediate vicinity of a caseous mass 
connective-tissue overgrowth always 
occurs, and caseous masses may 
become encapsulated. Bile-duct 
tubercles occur along the course of 
these tubes, and may ulcerate into 
the lumen; such areas are apt to be 
stained by bile. Miliary tuberculosis of the capsule of the liver k not 
rarely occurs in tuberculous peritonitis. 

Syphilis is met with in the form of diffuse infiltration and cirrhosis, 
or in the form of gummata. Either of these varieties may be found as 
a result of acquired or of hereditary syphilis. In the diffuse form the liver 
presents much the same appearances as in atrophic cirrhosis, but as the 
connective-tissue bands are much more pronounced, the liver is prone to 
be irregularly contracted and lobulated — hepar lobatum (Fig. 335). 
Gummata may occur in any part of the organ, and may be single or 
multiple, massive or miliary, presenting themselves as rounded, yellow- 




Fig. 334. — Miliary tubercles in the liver. 



DISEASES OF THE GASTROINTESTINAL TRACT 



705 



ish, or grayish areas, ofttimes showing central necrosis and surrounded 
by connective-tissue hyperplasia (see Fig. 133). Complete cicatrization 
may lead to decided scar formation. In addition to these forms, con- 
genital syphilis may manifest itself in the form of a uniform, diffuse con- 
nective-tissue hyperplasia and round-cell infiltration. The liver-cells 
are pushed apart and are ill-developed or atrophic (Fig. 336). 




Fig. 335. — Syphilitic cirrhosis of the liver: lobulated liver (Kast and Rumpel). 

i 




Fig. 336. — Diffuse congenital syphilis of the liver. 



Leprosy occasionally affects the liver, causing the formation of 
nodular masses. 

Actinomycosis, primary or secondary, occurs in the liver as. single 
or, more commonly, multiple abscesses with granular necrotic contents, 
surrounded by a productive deforming connective tissue, and tending 
to cause adhesions through which the process travels to adjacent struc- 
tures. 

45 



706 



A TEXT-BOOK OF PATHOLOGY 



TUMORS 

Fibromata, lipomata, and myomata are occasionally observed as 
nodular masses, but have little significance. 




Fig. 337. — Section through a large nodule of sarcoma of the liver, showing the practically 
normal liver substance above, and the sarcoma with central softening below. 

Angioma is an important tumor occurring upon the surface of 
the organ; it is usually of small size, rarely exceeding that of a wal- 
nut. It is more commonly found in persons who have died at advanced 
years than in young persons. Angiomata appear as dark-red or bluish , 



DISEASES OP THE GASTKO-INTESTINAL TRACT 



707 



slightly elevated areas, either sharply outlined and encapsulated, or 
merging gradually into the surrounding tissue,; Microscopically, they 
are found to be cavernous angiomata or cavernomata, not true tumors, 
and doubtless owe their origin to dilatation of the capillaries, with coin- 
cident atrophy of the liver-cells. Some are associated with hyperplasia 
of the vascular endothelium and belong to the hemangio-endotheliomata. 

Various explanations have been given for these tumors, among the 
theories being developmental defect, capillary distention, and true 
neoplastic growth. Only those associated with endothelial change can 
properly be called neoplasms. 

Sarcoma of the liver may occasionally be primary, but is exceed- 
ingly rare (Fig. 337). Secondary sarcoma, on the other hand, is very 
common, especially the melanotic form following primary sarcoma of 
the eye. Hemangioendothelioma, forming nests like sarcoma, has been 
reported as a tumor of early life possibly congenital in origin. 




r t 

Fig. 338. — Cirrhotic cancer of the liver (Hanot and Gilbert). 

Lymphadenomata are frequent in the liver in the course of the 
generalization of leukemic lymphadenoma; they are best considered as 
mere infiltrations of lymphocytes consequent upon the enormous leuko- 
cytosis of this disease, but they may represent, of course, hyperplasias 
of preexisting lymph-cell collections. 

Adenoma of the liver is met with in several forms. There may be 
either nodular masses, more or less encapsulated and of grayish-white or 
pinkish color, or a form of diffuse infiltration of the liver substance by 
encapsulated nodules of similar character. The histology of the con- 
stituent nests approaohes that of the liver lobules or of the tubules and it 
is not uncommon to find the cells cuboidal, with deeply staining nuclei. 
These variations render a differentiation from cirrhotic cancer difficult or 
even impossible. A fibrous tissue capsule may surround the nodule or 
connective tissue may be diffusely increased in the vicinity. 



708 



A TEXT-BOOK OF PATHOLOGY 



Carcinoma of the liver is rather rare as a primary tumor, but, like 
adenoma, may be nodular or diffuse. The nodular or massive cancer 
appears as a single mass of varying size, ofttimes surrounded by local 
metastatic nodules. On section, the color is grayish or pinkish, and there 
may be central necrosis and softening. Diffuse hepatic cancer occurs as a 
widespread and more or less uniformly distributed infiltrating and nodular 
growth. Not rarely in such cases there is associated cirrhosis, and the 
macroscopical appearance of the liver may be strikingly like that of an 
ordinary cirrhosis, though the liver is sometimes much enlarged (Fig. 
338). The terms cirrhotic cancer and cancer with cirrhosis have been 
applied to this form. Finally, the diffuse form may surround and spring 
from the periportal structures, and may ramify in the form of an inter- 
lobular infiltration. Microscopically, the cancers are simple . or 
adenomatous. 




Fig. 339. — Metastatic nodules of carcinoma on the surface of the liver (Hanot and Gilbert) . 

Formation and Structure of Adenomata and Carcinomata. — Micro- 
scopically, there is no sharp dividing-line between these growths. The 
adenomata present tubular formations of a more or less elongated and 
tortuous character, composed of cylindrical or of more irregular-shaped 
epithelial cells. In some instances these are strikingly like new-formed 
biliary capillaries, and perhaps they occasionally originate from these 
structures. More commonly, however, the origin would seem to be 
from the hepatic cells themselves. The columns of hepatic cells undergo 
proliferative change, and at the same time become somewhat trans- 
formed, assuming the tubular arrangement of adenoma. Occasionally 
adenoma and cystic adenoma originate from the mucous glands of the 
larger biliary ducts. When cirrhosis is associated with adenomatous 
proliferation it is probable that the primary change is a cirrhotic over- 
growth which induces secondary hyperplasia of the epithelial cells, in- 
stead of degenerative changes, such as usually result from the pressure of 
new-formed fibrous tissue. 

Carcinoma of the liver is similar in origin and structure to adenoma. 
The cellular acini and tubules are more irregular, and there is an evident 
tendency to diffuse infiltration and atypical formation of acini. 



DISEASES OF THE GASTROINTESTINAL TRACT 



709 



Metastasis is uncommon but has been seen in the lungs. The action 
of these tumors depends upon their size and position. • Besides the evi- 
dences of malignancy, the degree of impairment in liver function depends 
upon the amount of tissue destroyed and the pressure upon blood-vessels 
and bile-ducts. General jaundice is rare but visceral jaundice is rather 
common. 

Secondary carcinoma of the liver is very common as a result of 
carcinoma of the stomach or of other parts of the portal distribution. 
It is usually due to cancerous embolism in the portal capillaries, with 
subsequent development of the emboli. The liver becomes enlarged, and 
presents nodular masses upon its surface or within its substance. These 




Fig. 340, — Metastasis of pyloric carcinoma in liver. 

nodules vary from the size of a pea to that of an apple, and are frequently 
sharply delimited by capsule formation, especially those which have 
reached considerable size (Fig. 340) . Not rarely the nodules are indented 
upon the surface (umbilicated) from central softening or from contraction 
of fibrous tissue within (Fig. 339). Secondary cancer of the liver may 
also result from direct extension of cancer of the stomach or of the gall- 
bladder and biliary ducts. In all cases the new growths tend to compress 
the bile-ducts and lead to biliary pigmentation of the liver substance, 
and sometimes to general icterus. 

Chorion epithelioma and hypernephroma have been seen in the liver, 
probably as the result of embryonic defects. 

Cysts of the liver are rare. They may spring from the biliary ducts 
which have suffered simple dilatation, or from the mucous glands of the 
larger bile-ducts (cystic adenoma). Occasionally small cysts are seen 



710 



A TEXT-BOOK OF PATHOLOGY 



which suggest origin from dilatation of the lymphatic channels. A 
condition similar to the multiple cystic kidney has been seen in the 
liver. It has been so often congenital that formation defects have been 
held responsible; some observers have looked upon it as neoplastic. 

PARASITES 

Of the protozoa, coccidial psorospermioz (Fig. 341) have been occa- 
sionally demonstrated in the human liver in small nodular tumors; but a 
more important parasite is the Entamoeba histolytica, occurring in abscess 
of the liver secondary to amebic dysentery. The pus of the abscess may 
contain immense numbers of the amebse, and doubtless these Organisms 
bear an important relation to the lesion, perhaps causing necrosis by 
their own activity and then liberating pyogenic organisms which they 
have carried from the intestines, and which complete the pathological 
process. The larval Linguatula rhinaria is occasionally met with. 




Fig. 341. — Coccidia in the wall of a bile-duct. The cut shows in the center active pro- 
liferation of the wall of the duct, with numerous ovoid coccidia massed in the tissue. 

The Fasciola hepatica and the Dicrocoelium lanceatum occasionally 
infest the biliary ducts, and the Schistosoma haematobium the portal vein. 
Ascarides sometimes creep upward in the biliary ducts as far as the 
branches within the liver. The Cysticercus celluloses is a rare parasitic 
formation. 

Echinococcus Cyst. — The most important parasitic disease of the 
liver is the echinococcus cyst, caused by the presence of the larva? of the 
Taenia echinococcus (see Part I). This parasite occasions cystic forma- 
tions of various kinds within the liver. The cyst has a double wall: the 
outer, of connective tissue; the inner, a parenchymatous membrane, 
from which buds (brood-capsules) and secondary cysts are prone to 
originate. There may be a single cyst containing clear liquid of low 
specific gravity, or a mother-cyst containing daughter-cysts, either upon 
the inner wall or floating free within the liquid after their separation. 
Sometimes even granddaughter-cysts are formed. Occasionally the 
daughter-cysts are found outside of the mother-cyst, extrusion in such 



DISEASES OF THE GASTROINTESTINAL TRACT 



711 



cases having taken place. A form of multilocular cyst is more rarely 
observed in which there are numerous small cysts embedded in more 
or less firm connective tissue (Fig. 342) . Echinococcus cysts may rupture 




Fig. 342. — Echinococcus multilocularis (Luschka). 

into^thefabdomen or into surrounding viscera. The most serious condi- 
tion isjrupture into the vena cava, as the result of which hydatid disease 
of the heart, the brain, or other organs may ensue. Bacterial inva- 
sion^occasionally takes place, and abscess may result. Finally, the 




Fig. 343. — Echinococcus cyst of the liver (from a specimen in the Museum of the Phila- 
delphia Hospital). 

liquid contents may be absorbed, and the cyst may be reduced to a small 
cavity having a shrivelled wall and containing granular or caseous 
detritus (Fig. 343). Echinococcus cysts may press upon the gall-duct, 
producing jaundice, or upon the portal veins, causing ascites. 

The Biliary Ducts and Gall-bladder 

inflammations 

Cholangitis, or inflammation of the biliary ducts, is most fre- 
quently secondary to duodenal catarrh, though it may be the result of 
direct irritation by gall-stones, by foreign bodies which have entered from 
the intestine, or by parasites or bacteria. In the cases secondary to duo- 
denitis the inflammation usually extends but a short distance upward 
from the mouth of the common bile-duct, but there may sometimes be 
more extensive involvement of the ducts, and the mucous membrane of 



712 



A TEXT-BOOK OF PATHOLOGY 



the gall-bladder may be affected at the - same time. The mucosa is 
swollen, more or less edematous, and secretes abundant mucus. The 
result is obstruction of the duct with retention of bile, and consequent 
jaundice. 

Suppurative cholangitis may occur as an independent condition in 
consequence of certain infectious diseases, but is more commonly sec- 
ondary to obstruction of the common duct or hepatic duct. Bacterial 
invasion from the intestine or through the blood causes decomposition 
of the retained bile and inflammation of the ducts. Sometimes sup- 
purative cholangitis results from the rupture of an abscess of the liver 
into the bile-ducts. The association of cholangitis, simple or sup- 




Fig. 344. — Purulent cholangitis, showing suppuration following the biliary tract from 
the hilus, and producing abscesses, one in section (from a specimen in the collection of 
Dr. Allen J. Smith). 

purative, with typhoid fever is of considerable clinical interest. Among 
the micro-organisms discovered in suppurative cholangitis the pyogenic 
micrococci and the Bacillus coli communis are most frequent. The bile- 
ducts are filled with more or less decomposed bile or with puriform 
liquid, and the walls of the ducts, especially the larger ones, may present 
an ulcerated or necrotic appearance. Retention of bile and jaundice 
result early. Small dilatations may occur in places where the duct has 
become deeply ulcerated, and later hepatic abscesses of considerable size 
may form (Fig. 344). 

Chronic cholangitis may be the outcome of an intense acute attack 
or repeated acute attacks, but is more commonly met with as a conse- 
quence of chronic obstruction of the ducts and retention of bile. A local- 
ized form, causing cicatricial stenosis, results from intense inflammatory 
lesions following the passage of stones. The gall-ducts in chronic cholan- 
gitis are more or less thickened, and in the cases due to obstruction may 
be considerably dilated. 



DISEASES OF THE GASTROINTESTINAL TRACT 



713 



Results of Cholangitis. — In the acute form extension may take 
place to the ducts within the liver, and in case of bacterial invasion 
pericholangitis and abscesses may form. More commonly acute cholan- 
gitis leads to but a temporary overfilling of the biliary capillaries with 
bile, and, in consequence, to obstructive jaundice. When the obstruction 
is continued for a considerable length of time, reactive changes occur in 
the liver, constituting the form of cirrhosis called " biliary cirrhosis" (see 
p. 701). 

Cholecystitis, or inflammation of the gall=bladder, may result 
from extension of cholangitis, or may be due to the irritation of re- 
tained bile or of gall-stones. If it should be primary, the communicat- 
ing bile-ducts are soon involved. It is a fairly common sequel of typhoid 
fever, and the typhoid bacillus has been found in the contents of the 
gall-bladder, sometimes a considerable time after the original infection 
had subsided. In this subacute or chronic typhoid cholecystitis and 
in similar conditions there is a mild hypertrophic catarrh. This permits 
the bacteria to hide in the depths of the membrane more securely. The 
epithelium is often loosened or set free, and, with the abundant mucus, 
forms a nucleus for gall-stones. The acute inflammation is prone to 
assume a purulent character, and the gall-bladder may become filled with 
pus (empyema of the gall-bladder). This may rupture, discharging into 
the abdominal cavity, into adjacent viscera, or externally. The wall of 
the gall-bladder is usually much thickened and the mucous membrane 
is swollen and ulcerated. The dependent position of the sac favors 
retention of exudate and involvement of the serous coat, which may 
eventually lead to adhesions with adjacent organs if the infection be 
not of a kind to cause rapid suppuration. If, however, the condition 
be actively suppurative, fistulous tracts may be established with other 
viscera. If bile escape into the peritoneum, inflammation and necrosis 
arise. The results of long-continued non-suppurative cholecystitis are 
either distention by complete blocking of the outlet and, retention of 
the contents when the mucosa continues to produce an exudate, or an 
atrophic fibrosing change in the wall, whereby the organ shrivels. 

STENOSIS AND DILATATION 

Stenosis of the bile-ducts is most commonly the result of acute 
inflammation, causing thickening of the mucosa and accumulation of 
mucus. It may result from chronic cholangitis with cicatricial over- 
growth of connective tissue; from the impaction of gall-stones, or the 
presence of various foreign bodies, such as particles of food, mucus, 
round-worms or other parasites within the duct; from pressure by aneu- 
rysms, by tumors of the head of the pancreas, pylorus, duodenum, 
lymphatic glands, or of the liver; and from tumors of the gall-ducts 
themselves. Sometimes it is due to the constriction of adhesions result- 
ing from peritonitis. Obstruction of the ducts leads to the retention 
of bile and dilatation of the ducts above, with consequent enlargement 
of the fiver and jaundice. Obstruction of the cystic duct, which is most 
frequently due to the impaction of a stone, may occasion dilatation 
of the gall-bladder with dropsical liquid, in consequence of the passive 
hyperemia produced by compression of the veins at the neck of the 



714 



A TEXT-BOOK OF PATHOLOGY 



gall-bladder. This condition is spoken of as dropsy of the gall-bladder. 
Sometimes suppurative inflammation occurs, and empyema of the 
gall-bladder results. - 

Congenital atresia of the gall-passages is a rare condition ascribed 
to antenatal interlobular cirrhosis, due to toxins entering through the 
placenta. It gives the changes mentioned above and causes death in 
the first year. 

Contraction of the gall=bladder, or even complete shrinkage or 
atrophy, may result from obstruction at the mouth of the cystic duct, 
or from inflammatory processes within its walls or surrounding it. 




Fig. 345. — Suppurative pylephlebitis, showing infiltration around the bile-ducts and, 
in places, as at (a) , a breaking down of the duct and the surrounding tissue to form necrotic 
abscess cavities. 

Dilatation of the ducts or of the gall-bladder most frequently 
results from any stenosis of the ducts below. When in the bile passages 
of the organ proper, the results depend somewhat upon the completeness 
of obstruction and the area involved. If a stone close the hepatic duct, 
general dilation occurs but this may be relieved and no permanent 
widening appear. If the obstruction be permanent, or partial and con- 
tinuous a generalized or localized " dropsy of the bile-ducts" may result. 
The fluid in these cases is usually palely bile stained, watery or mucoid. 
Cysts rarely appear from such a causation but a diffuse ectasia of the 
ducts is the usual result. 

GALL-STONES; CHOLELITHIASIS 

Gall-stones are concretions resulting from inspissation of bile, or 
from the deposit of various substances from the bile. Most frequently 
they are formed in the gall-bladder; occasionally they originate in the 
bile-ducts. 

Etiology. — The causes are imperfectly understood. Advanced 
years, the female sex, sedentary life, and high living seem to be factors 
of importance. Inflammatory conditions leading to obstruction and 
retardation of the outflow of bile, and also to desquamation of epi- 
thelium, which, with mucus, serves tojform the nuclei of the stones, 



DISEASES OF THE GASTROINTESTINAL TRACT 



715 



seem to be among the causes. Besides these conditions there are prob- 
ably indefinite alterations of the bile which permit of precipitation 
of some of its constituents, notably cholesterol. Bacteria play an im- 
portant role in many cases. The bacteria may by their precipitation and 
clumping form the nucleus of a stone, or may occasion decomposition of 
the bile and inflammation of the ducts. Desquamated epithelial cells 
and products of decomposition of the bile in the latter case form the 
nucleus of the gall-stone. Among other micro-organisms the typhoid 
and colon bacilli are of etiological importance. They are able to live for 
long periods in the gall-bladder. 




Fig. 346. — Gall-bladder from a case of chronic cholecystitis with cholelithiasis. The 
interior of theTgall-bladder is shown with its ribbed projections and intervening pouches, 
in which small and large gall-stones had been lodged. 

Structure and Pathological Anatomy. — Gall-stones may be single 
or multiple, and may vary in size from minute granular particles of 
biliary sand to calculi several centimeters in diameter. When single 
they occur as rounded or oval masses ; when multiple they are prone to 
be marked with facets; when formed within the bile-ducts they are 
elongated. Biliary sand is, for the most part, composed of biliary pig- 
ments, bilirubin in combination with calcium salts. Calculi are classi- 
fied by Aschoff in the following groups: (1) Round, gray-white, irregular, 
translucent, dull stones with a glistening, radiating internal surface; 
they may at times be cut; are usually single or double; these are the 
radiate cholesterin stones. (2) Laminated cholesterin calcium stones, 
of smooth surface and dull white or yellowish color, constructed on a 
finely granular or crystalline basis. (3) Stones of cholesterin, pigment and 



716 



A TEXT-BOOK OF PATHOLOGY 



calcium, the color, size and shape varying with the proportion of these 
elements, ranging from yellow to black, granules to large masses, and 
round to faceted, being smooth or uneven; they are usually concen- 
trically laminated. (4) Combined stones of radial and laminated charac- 
ter of the second and third varieties, appearing with these forms or 
separately, singly or in pairs with smooth or facetted surface. The 
second, third and fourth are the commonest varieties of gall-stones and 
appear most often in the presence of chronic inflammation. (5) Calcium 
bilirubinate stones. These appear much more commonly in the intra- 
hepatic ducts and may be responsible for suppurative or chronic cholangi- 
tis and jaundice. (6) Calcium carbonate stones-pale, nodular, finely 
crystalline but with irregular cut surface. 

It seems that when stones form in a bladder that has been isolated 
from the liver by fibrous tissue or compression, they are usually choles- 
terol derived from the bladder wall. On the other hand, when there is 
continued inflammation, but with no hindrance to the ingress of bile 
from the liver, stones contain more bile-pigments, precipitated by bacteria 
probably, and calcium salts from the imflammatory exudate. 

Gall-stones may lie in the gall-bladder or ducts without causing 
serious disturbances, or from time to time attacks of biliary colic denote 
their passage through the ducts to the bowel. They may pass through 
the ducts into the intestine when of small size, but often become im- 
pacted in the lower part of the common duct, generally just above 
the duodenal papillae or in the mouth of the cystic duct. Secondary 
changes in the gall-bladder (dilatation and inflammation) and in the 
liver (enlargement, cirrhosis) may result; and the stone may cause local 
ulceration, and may finally escape into the bowel or into other parts by 
ulceration. Occasionally gall-stones remain impacted for long periods 
without causing - serious disturbances, enough space remaining to per- 
mit the escape of bile. 

TUMORS 

Tumors of the biliary tract are more common than formerly thought, 
and are almost always malignant epithelial growths. Primary carci- 
noma arising from the mucous glands, either at the fundus or neck, which 
places are those at which a stone would exercise most pressure, is the most 
important. It is usually columnar-celled carcinoma of the adenoma type 
but hornifying tumors are not uncommon. It appears as an irregular 
elevation of the mucous surface, and rapidly infiltrates the adjoining 
parts. In cases of primary cancer of the gall-bladder the liver is soon 
involved. Gall-stones are present in a great majority of the cases and 
probably play an important etiological part by their continuous irritation. 
On the other hand, the gall-stones may form in consequence of the stag- 
nation of bile and other local conditions caused by the tumor. Carcinoma 
sometimes begins at the junction of the two main ducts or in the ampulla 
of Vater. In the latter situation it can cause obstruction of the pancreatic 
duct as well as of the bile passages. Secondary carcinoma of the gall- 
bladder or ducts most frequently results from cancer of the liver. The 
lower end of the duct may be involved in cases of carcinoma of the papilla 
of Vater. Sarcoma, fibroma, and other tumors are rare. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



717 



JAUNDICE 

Jaundice, or icterus, is a discoloration of the skin and other parts* 
resulting from the presence in the blood of biliary pigments. 

Etiology. — Jaundice has been described as being of two forms: the 
obstructive mechanical or hepatogenous, and the non-obstructive or hematog- 
enous variety. This distinction has been questioned on the assump- 
tion that bilirubin can only be formed in the liver. Late observations 
would seem to indicate that under certain circumstances such a process 
may occur elsewhere in the body, thus strengthening the above classi- 
fication. 

Among the distinctly mechanical causes of jaundice the most fre- 
quent is occlusion of the ducts by catarrhal duodenitis and cholangitis. 
To this form the term catarrhal jaundice is generally applied. Less 
commonly obstruction may be occasioned by foreign bodies, gall-stones, 
or parasites within the ducts ; by the pressure of tumors of the duodenum, 
pancreas and the lymphatic glands of the liver, or of the gall-ducts 
themselves; by the pressure of aneurysms upon the ducts; or by occlu- 
sion of the biliary passages within the liver by abscess, hydatid cysts, 
hypertrophic cirrhosis, carcinoma or other tumors. Congestion of the 
liver may lead to jaundice by the swelling of the organ consequent upon 
the overfilling of the vessels with blood, or by reason of the resorption of 
bile due to the alterations of pressure of the blood in the different vascu- 
lar channels. Hematogenous jaundice was formerly regarded as due to 
disintegration of the blood in the general circulation, but it is now recog- 
nized that formation of the pigments normally takes place in the liver, 
the cells of that organ breaking up hemoglobin, keeping the iron, and 
using the rest of the pigment as bilirubin. From late experiments of 
Whipple and Hooper it seems that under certain circumstances bilirubin 
may be formed without the function of the liver, but elsewhere, possibly 
by endothelium, so that a true hematogenous jaundice arises. There are 
instances of jaundice in which active hemolysis in the circulation is an 
element of importance, probably when the liver cannot care for all the 
liberated pigment as indicated above. Jaundice of this character occurs 
in various severe infections, such as yellow fever, acute yellow atrophy 
of the liver, in familial hemolytic icterus, the jaundice of the newborn, 
and in consequence of certain intoxications (phosphorus, toadstools, the 
venom of snakes) . Several explanations may be applied to cases of this 
kind. Sometimes excessive blood destruction leads to formation of 
abnormally large quantities of bile (polycholia) , and, in consequence, to 
absorption of biliary pigment by the lymphatics in the liver. It is be- 
lieved by some investigators that the hepatic cells may in some conditions 
reverse the dhection of their secretion, so that the bile is discharged into 
the lymphatic current instead of into the biliary capillaries. This view 
needs confirmation. In other cases toxic degeneration of the hepatic cells 
may lead to stimulation of the hepatic function, or to swelling of the cells 
and compression of the biliary capillaries, and, in consequence, to absorp- 
tion of the bile. Finally, in the jaundice of the newborn, as well as in 
some instances of sudden emotional jaundice, disturbance of the circula- 
tion within the liver may be a potent cause. 



718 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy. — Microscopical examination of the liver may 
show the biliary capillaries distended with bile in casts, like the cylinders 
within the tubules of the kidney in nephritis, and the hepatic cells them- 
selves more or less pigmented by coarse, irregular, green-brown masses. 
The collections are seen within ducts in obstructive jaundice whereas 
in the hemolytic variety they are irregular in distribution, the cells of the 
liver usually being more affected. The bile is absorbed by the lymph- 
atics, and ultimately reaches the general circulation and pigments the 
tissues. The earliest evidence is seen in the intima of the vessels; later, 
all the tissues and organs of the body may be involved, and visible dis- 
coloration appears in the skin and external mucous membranes. The 
urine is dark brownish or greenish in color, and all of the secretions 
and liquid exudates may be pigmented. In cases caused by obstruction 
of the bile-ducts the bile cannot reach the intestines and the stools have 
a quite characteristic putty color. In "hematogenous" jaundice the 
color of the stools is to a certain extent maintained, bile secretion being 
not necessarily stopped. Intense disturbances, especially of the nervous 
system, result from excessive cholemia, but are due to the cholic acid 
salts rather than to the biliary pigments. The coagulation time of the 
blood is much lengthened, and bile salts have a dissolving effect upon 
endothelium. These facts help to explain the hemorrhages frequently 
seen with icterus and the prolonged bleeding after operation in cases where 
it exists. 

The Pancreas 
congenital abnormalities 

Complete absence has been met with in monstrosities. More fre- 
quently an adventitious pancreas or heterotopic pancreatic tissue is 
observed. Small nodules of pancreatic tissue may be found in the 
omentum, the wall of the intestines, or elsewhere. In a small percentage 
of cases the duct of Santorini is present as a tube of appreciable size dis- 
charging into the duodenum. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs during digestion and in association with 
acute inflammation. 

Passive hyperemia occurs in cases of obstruction to the portal 
circulation, but rarely leads to notable changes. The grayish-blue color 
is characteristic. 

Hemorrhage may occur in the pancreas, in the form of minute 
petechise or diffuse hemorrhagic infiltration, as the result of passive 
congestion or of various hemorrhagic and infectious diseases, such as 
purpura, scurvy, septicemia, or the extreme anemias. 

Large hemorrhages occur in what is called "acute hemorrhagic pan- 
creatitis." By some the inflammatory nature of this condition is denied, 
but because of the cellular and serous infiltration accompanying it we 
prefer to describe it under pancreatitis and to call the hemorrhage with- 
out any infiltration "pancreatic apoplexy." Moreover, it is probable 
that some infection, recent or remote, has induced it (see below). Trau- 
matic hemorrhage does occur. ( 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



719 



Pancreatic apoplexy is a suddenly appearing destructive hemorrhagic 
extravasation into the organ without preceding inflammatory change, 
said to be due most often to alcohol, at times following injury, and 
occasionally occurring without discoverable cause. 

Sudden death may occur in these conditions from shock or compres- 
sion of the solar plexus, or the case may terminate in other pancreatic 
affections. Doubtless chronic indurative pancreatitis originates in this 
way in some cases. When not actually fatal, but still considerable 
damage to the circulation has been done, progressive necrosis and sup- 
purative inflammation terminate the disease. 

ATROPHY AND DEGENERATIONS 

Atrophy of the pancreas occurs in old age and as the result of maras- 
mic conditions. The entire organ is involved in such cases. Localized 
atrophy may be associated with various degenerations or other diseases 
of the organ. Thus, in carcinoma or in cirrhosis, pressure-atrophies are 
extremely frequent. 

Parenchymatous degeneration may occur in consequence of acute 
infections, and resembles the cloudy swelling of the liver, kidneys, and 
heart occurring in the same diseases. The organ becomes somewhat 
enlarged, is softer than normal, and may at the same time be con- 
gested. Microscopically, the cells are found to have undergone granular 
change (parenchymatous degeneration). 

Amyloid infiltration is a rare condition occurring in association 
with amyloid disease of other organs. 

Pigmentation may be met with in the atrophic organ of old persons, 
or in consequence of hemorrhagic infiltration and subsequent disorgani- 
zation of the extravasated blood. Of particular interest are the cases of 
hematochromatosis affecting the pancreas, together with the intestines, 
liver, and other abdominal organs in drunkards. The affected organs in 
this condition present more or less extensive hematogenous pigmentation. 

Necrosis of small areas of the pancreas may occur in consequence 
of hemorrhagic or of inflammatory conditions. Sometimes the entire 
organ is disorganized by a form of gangrenous necrosis, especially in cases 
of pancreatitis resulting from perforation of a gastric ulcer or from ex- 
tension of other severe inflammatory lesions. This is a form of self- 
digestion due to active enzymes, liberated either by disturbance of the 
blood-supply or infection. Autolysis may occur at times as a post- 
mortem change. 

Disease of the Islands of Langerhans. — The pancreas normally 
contains small collections of round cells differing very strikingly from 
the true pancreatic cells. They are more abundant near the tail than 
the head of the organ. They are not in relation with the excretory ducts 
of the organ, but rather with the blood-vessels, and are supposed to 
make an internal secretion. Atrophy and hyaline degeneration of these 
islands have been described in association with chronic interstitial 
pancreatitis and as independent conditions. The relation of such lesions 
to diabetes is discussed below. 

Fat necrosis is a form of degeneration or necrosis peculiar to the 
tatty tissue of the pancreas and of the omentum. Most frequently 



720 



A TEXT-BOOK OF PATHOLOGY 



it is found in association with acute or chronic pancreatitis, with tumors 
of the pancreas, or obstruction of its duct; but it may occur inde- 
pendently, and it may appear in the fatty tissue of the omentum with- 
out involving the pancreas. Minute foci, having a gray or white, 
opaque appearance, or, more rarely, larger areas due to confluence of small 
foci of necrosis, are found in the adipose tissues. Hemorrhagic infiltra- 
tion may be associated, and sometimes extensive hemorrhage may 
ensue. Inflammation of the pancreatic tissues around the foci of 
necrosis is common, and in some instances extensive disorganization 
(necrosis) of the pancreas occurs. 

Microscopically, the changes consist of, first, disintegration of the 
fat-drops of the adipose cells with formation of small droplets, then 
the appearance of fat-crystals within the adipose cells, and subsequently 
the disorganization of these and the formation of calcium salts of the 
fat-acids, the microscopical appearance at this stage being that of in- 
definite granular or translucent masses. The nature of fat-necrosis has 
been previously discussed (see p. 117). 

INFLAMMATIONS 

Pancreatitis may be acute or chronic. The acute variety present? 
itself in different forms, the most frequent being the hemorrhagic and 
the suppurative or necrotic. Chronic pancreatitis is analogous to 
chronic hepatitis, and leads to similar induration or cirrhosis. 

The sources of infection of the pancreas must be the blood, lymph, 
and pancreatic duct, of which the last seems the most important. In 
disturbances of the duodenum bacteria may pass from the ampulla of 
Vater along Wirsung's duct to the gland, and it has been shown that bile 
may also follow this course. Either of these factors can produce in- 
flammation of the duct, its sheath or adjacent acini, and lead to altera- 
tions in blood-supply to the whole organ or isolated lobules. These 
facts are important to remember in studying the diseases of the pancreas. 
It is also possible for inflammation to begin in the organ by extension 
along the periductal lymphatics, especially in the presence of an infection 
in the deep mucosa of the duodenum. In some quarters it is believed 
that the firm nodular chronic inflammation of the head of the pancreas 
always arises in this manner. In all forms of pancreatitis the existence of 
biliary calculi should be sought, as stones and sand, especially in Vater's 
ampulla, seem to predispose to affections of the organ. 

Acute hemorrhagic pancreatitis occurs most commonly in young 
persons, and is probably in most, if not all, cases dependent upon in- 
fection of the pancreas through its ducts, in the presence of conditions 
favoring obstruction of the lumen and the admission of bile. It is possible 
that some cases are not actively inflammatory, but simply instances of 
degenerations of the pancreas, with hemorrhage and round-cell infiltra- 
tion as consequences. The pancreas is swollen, especially at its head; the 
lobules are enlarged and the interlobular tissues compressed. Hemor- 
rhagic infiltration is a constant condition, but variable in extent. Micro- 
scopically, the cells of the pancreas are swollen, and usually present 
the appearances of parenchymatous degeneration. The interlobular 
tissues are infiltrated with round cells. Localized necrosis and fat- 



PLATE 14 




Acute hemorrhagic pancreatitis showing fat necrosis. 



DISEASES OF THE GASTROINTESTINAL TRACT 



721 



necrosis may be associated. Gangrenous pancreatitis is frequently 
described, but this form is probably not a special variety, being more 
likely a severe grade of the hemorrhagic disease ; it is not peculiar in 
causation. Rapid death is the usual consequence, but it is probable 
that some of the cases terminate in chronic pancreatitis. There is edema 
or hemorrhage into the capsule, which may escape to the peritoneum by 
osmosis or rupture, carrying pancreatic enzymes with it. 

It is believed that the pancreatic secretion itself plays the chief role 
in the causation of this condition, since a ligation of Wirsung's duct will 
bring about an analogous inflammation. If local areas have been the 
seat of inflammation or edema, cellular necrosis will liberate the pan- 
creatic enzymes, of which steapsin will at once attack the neighboring- 
fat, causing fat-necrosis, while trypsin will erode blood-vessels, per- 
mitting edema or hemorrhage. 

Acute suppurative pancreatitis may result from direct extension of 
septic processes in the neighborhood, as in gastric or duodenal ulceration, 
purulent collections in the peritoneum, and the like. It may also occur 
as an independent affection, most frequently in consequence of infection 
from the intestinal tract through the ducts, or as the effect of 
pyogenic cocci operating in an organ devitalized by acute hemorrhagic 
pancreatitis. Occasionally metastatic abscesses are observed in the 
pancreas. Hemorrhagic pancreatitis may be converted into the 
necrotic form in consequence of extensive extravasation of blood and 
secondary infection. 

The organ presents a variable appearance, according to the cause 
and extent of the process. There is generally marked swelling with 
more or less softening, and not rarely necrotic foci. Complete gangrene 
or necrosis is an occasional termination. In other cases parts of the 
pancreas may slough, the cast off part being retained as a sequestrum 
or discharged through the intestines or into the peritoneum, setting up 
fatal peritonitis. The great edematous swelling of the capsule in both 
the foregoing forms is worthy of emphasis. 

Chronic indurative pancreatitis, or cirrhosis of the pancreas, may 
be hematogenous in origin, resulting from syphilis and alcoholism, or 
it may be caused by prolonged irritation exercised through the pan- 
creatic ducts, calculi, either biliary or pancreatic, in consequence of 
frequent entrance of intestinal contents or partial stenosis of the ducts. 
In the latter case it may be secondary to duodenal catarrhs or obstruc- 
tions of the pancreatic duct. In some cases it is doubtless the outcome 
of acute attacks. 

The pancreas in the earlier stages is enlarged and hard, especially 
at the head, where the firmness may be that of scirrhus cancer. On 
section it may present a homogeneous structure and may be of car- 
tilaginous consistence. Macroscopically, the tissues between the acini 
are visibly infiltrated and hyperplastic, the amount of connective tis- 
sue being greatly in excess of the normal. In the later stages the organ 
becomes contracted, and may be considerably reduced in size and of 
stony hardness. 

Microscopically, the parenchyma of the organ is found to be atrophied 
or degenerated in consequence of contraction of the hyperplastic fibrous 

46 



722 



A TEXT-BOOK OF PATHOLOGY 




Fx;. 348 — Interstitial pancreatitis involving the islets of Langerhans almost exclusively. 



DISEASES OF THE GASTROINTESTINAL TRACT 



723 



tissue. Fat-necrosis and fatty degeneration of the pancreatic cells are 
frequently associated. 

Interlobular and interacinar fibrosis have been described. The 
former, said to follow infection through the duct or obstruction by cal- 
culi, produces a hard nodular organ traversed by wide trabecular which 
compress the acini and islands of Langerhans. Interacinar fibrosis, 
believed to be due to alcohol and arteriosclerosis, occurs as a connec- 
tive-tissue overgrowth within acini and islets; the organ is smooth and 
of natural size. This form is seen frequently with hepatic cirrhosis and 
diabetes. 

Pathological Physiology of Pancreatic Disease. — Acute pan- 
creatic disease manifests itself by abdominal pain and distention, cyanosis 
and early shock and collapse; the last has been ascribed to intoxication 
with protein split products liberated by pancreatic ferments from the 
abdominal tissues they digest. Among the more or less characteristic 
symptoms of chronic pancreatic disease are fatty diarrhea (steatorrhea), 
imperfect digestion of proteins (azotorrhea), rapid emaciation, lipemia, 
and lipuria. All of these result from the cessation of pancreatic secretion 
and consequent disturbances of digestion and absorption of food. None 
of them is pathognomonic. A more important symptom is glycosuria, 
and the role of pancreatic disease in the pathology of diabetes is a leading 
one. Atrophy and carcinoma of the organ may be found in diabetes, but 
the commonest changes are hyaline necroses of the islets of Langerhans 
and more or less regularly distributed fibrosis. Whatever the nature of 
the disease, the result seems to be a disturbance of an internal secretion 
having importance in the consumption of sugar. When this secretion 
stops or diminishes, glycosuria or diabetes results. While many, indeed, 
probably most, cases of diabetes show pancreatic lesions either in acini or 
islets of Langerhans, there is no anatomical proof that disease of this 
organ is the cause of diabetes, although chemical studies connect the 
two physiologically. There seems to be an internal secretion of the 
organ, probably emanating from the islets, which has a part in carbo- 
hydrate metabolism. 

INFECTIOUS DISEASES 

Syphilis may occur in the pancreas in the form of indurative pan- 
creatitis or of gummata. The former may occur in adults, but is more 
common in the newborn, in association with indurative changes in the 
liver, lungs, and other organs. According to Stoerk there are, not only 
the evidences of syphilitic induration, but a perversion of the normal 
anatomy in the shape and arrangement of the essential acini while the 
islets of Langerhans remain about normal. 

Tuberculosis of the pancreas, in the form of miliary tubercles, may 
occur in cases of generalized tuberculosis, but this organ is one of the 
rarest seats of tuberculosis in the body. 

TUMORS 

Carcinoma. — Primary cancer may affect the head or, more rarely, 
other parts of the pancreas, and is of the glandular (scirrhus) or, more 
rarely, of the cylindrical-celled variety. Compression with secondary 



724 



A TEXT-BOOK OF PATHOLOGY 



cystic distention of the pancreatic duct and obstruction of the common 
bile-duct or of the veins (portal, superior mesenteric, and splenic) behind 
the head of the organ may result. Metastasis to the neighboring lym- 
phatic glands and to the liver is frequent. Secondary cancer may 
affect the pancreas by extension of cancer of the stomach or of the 
duodenum. 

Pathological Physiology. — Pancreatic carcinoma and other chronic 
diseases of the pancreas often occasion rapid emaciation, and sometimes 
fatty diarrhea, lipemia, and lipuria. In a mechanical way cancer of 
the head of the pancreas may cause jaundice by obstruction of the bile- 
ducts; splenic enlargement, intestinal congestion, diarrhea, and ascites 
by obstruction of the adjacent veins; repeated vomiting and sometimes 
intestinal obstruction by compression of the duodenum. 

Sarcoma is rarely primary. Secondary nodules are occasionally 
observed. Benign tumors are very occasionally seen. 

Cysts of the pancreas may be of several kinds. Dilatation from 
obstruction of the pancreatic duct or its branches may occasion a single 
cyst or multiple cysts filled with serous or gelatinous liquid. Hemor- 
rhagic cysts are sometimes the result of necrosis of portions of the organ, 
or a hemorrhage (hematoma) may be later converted into a serous 
cyst. The latter is the mode of formation of some of the large cysts, 
occurring, for the most part, near the tail of the pancreas. In other 
cases, it has been held, these cysts result from primary necrosis and 
subsequent digestion of the necrotic area by the pancreatic secretions. 
In rare instances cysts of the pancreas have a glandular structure of the 
papillary cystadenoma type. 

Cystic accumulations in the lesser omental cavity, resulting from 
localized peritonitis, may be difficult to distinguish from true pan- 
creatic cysts, as some of the latter lie more outside than within the 
pancreas. In some instances such localized peritonitis seems to be the 
result of extension of pancreatic inflammations or rupture of subcapsular 
collections. These have been called pseuclopancreatic cysts. 

The fluid of pancreatic cysts often contains a proteolytic and an 
emulsifying ferment, but the contents of other abdominal cysts may 
have similar constituents. 

The Pancreatic Duct 

Obstruction of the pancreatic duct may be due to tumors of the 
papilla in the duodenum or of the head of the pancreas, to calculi, to 
inflammatory thickening of the duct itself, or to the pressure of con- 
tracting fibrous tissue in chronic pancreatitis. Most commonly it leads 
to dilatation of the duct, this sometimes becoming so great as to occasion 
actual cystic formations (Fig. 349). The dilated ducts are filled with 
clear liquid, but sometimes through bacterial infection this is rendered 
turbid, or is actually converted into pus. Occasionally, small cysts, 
caused by distention of the finer divisions of the duct, are scattered 
through the organ {pancreatic acne). These are supposed to result 
from catarrhal processes in the ducts themselves. These small cysts 
are filled with clear or puriform liquid. Some cases so described are 
doubtless instances of fat-necrosis. In congenital atresia of the bile- 



DISEASES OF THE GASTROINTESTINAL TRACT 



725 



ducts there is frequently a similar condition in the duct of Wirsung. 
The duct of Santorini has been found stenotic also. 

Pancreatic calculi are composed of carbonate or phosphate of lime, 
and usually have an irregular shape. Wells suggests that in the presence 
of obstruction, calcium is obtained by a tryptic digestion of protein or 
from the exudation. They may occasion cystic distention of the ducts 
and abscess formation. 




Fig. 349. — Dilatation of the pancreatic duct and atrophy of the pancreas, due to calculi 

(Orth). 

The Peritoneum 
congenital abnormalities 

Absence of the peritoneum has been described; but more frequently 
minor defects, such as absence of the omentum or unnatural length 
of the omentum or mesentery, localized defects, fenestrations, and the 
like, have been observed. The peritoneal extension into the inguinal 
canal normally becomes occluded, but may remain patulous and may 
lead to congenital hernia. 

The defects of the peritoneum are not of great importance to this 
structure itself, but as it acts as a protective covering and support to the 
abdominal viscera, alterations in position, form, and function of the 
contents of the cavity result from congenital defects, e. g., enteroptosis 
from long mesentery. 

CIRCULATORY DISTURBANCES 

Active hyperemia may x occur in association with inflammation, 
or in the vicinity of lesions within the intestine which have not yet 
occasioned actual inflammation of the peritoneum itself. The affected 
part is bright red, the arterioles being distended and the endothelium 
somewhat swollen and elevated. 

Passive hyperemia is more frequent. It may be part of a general 
venous congestion, or may result from obstruction of the portal vein by 
thrombosis, cirrhosis of the liver, and similar conditions. The venules 
may be widely dilated, the deeper layers of the peritoneum somewhat 
edematous, and the lining endothelium swollen and loosened. Intense 
passive congestion may lead to ascites or to hemorrhage, 

Hemorrhage may occur in the form of punctate extravasation ins 
various septic and hemorrhagic diseases, and in parts adjacent to in- 
tense lesions, as in the peritoneum covering the bowel near anthrax 



726 



A TEXT-BOOK OF PATHOLOGY 



ulcerations. Hemorrhagic extravasations may likewise be due to 
intense passive congestion, as in death from suffocation or in obstruc- 
tions of the portal circulation. Certain forms of intoxication, like 
phosphorus-poisoning, snake-venom, or the like, may occasion petechial 
ecchymosis or large suffusions; and occasionally hemorrhagic extravasa- 
tions are due to embolic occlusion of the mesenteric arteries. Large 
hemorrhagic effusions may occur in the retroperitoneal tissues, espe- 
cially at the root of the mesentery, between the folds of the omentum, 
or elsewhere into the subperitoneal cellular tissues. These, as well as 
hemorrhages into the peritoneal cavity itself, are frequently traumatic 
in origin. Rupture of the spleen, of the liver, of the uterus or Fallopian 
tubes, or of aneurysms or superficial blood-vessels may be the immediate 
source of large hemorrhages. 

The extravasated blood within the cellular tissues undergoes gradual 
absorption, as elsewhere, and may leave pigmented areas and fibrous 
thickening. The blood within the cavity of the peritoneum may be 
directly absorbed, or may be gradually removed after clotting by de- 
generative processes and absorption through the lymphatic channels. 
Inflammatory reaction is wanting unless the blood mass is infected, 
although in Douglas' pouch it is rather the rule that hematoceles are 
formed by adhesions or the appearance of a coagulative capsule. Be- 
sides transudates, now to be described, air or bile may be found within 
the peritoneum, almost always resulting from rupture of some viscus. 
Gas, on rare occasions, is produced by some micro-organism. 

Dropsy of the peritoneum, or ascites, may occur as a part of a 
general anasarca in cardiac or renal disease, or may be due to obstruc- 
tion of the portal circulation, notably by cirrhosis of the liver. In these 
cases ascites may be absent at first from the freedom of the collateral 
circulation established between the branches of the inferior and supe- 
rior vena cava and the peripheral radicles of the portal circulation. 
Eventually, however, ascites ensues. In the earliest stages of certain 
cases of intense acute peritonitis and in chronic peritonitis, especially 
the tuberculous form, when the absorption of liquid from the perito- 
neum is disturbed by occlusion of the lymphatics, the liquid effusion 
may have a serous and not the ordinary inflammatory character. Chronic 
peritonitis plays a part in the etiology of many cases of ascites ordinarily 
regarded as the result of obstruction of the circulation alone, as in cases 
of cirrhosis of the liver. In such cases the venous stasis may occasion 
no dropsical exudation until a low-grade chronic peritonitis has devel- 
oped, when the membrane becomes more permeable and effusion results. 

An occasional cause of ascites is obstruction of the thoracic duct 
by new growths of its walls, thrombosis within, or pressure from the 
outside. The ascitic liquid in such cases frequently has a chylous char- 
acter. Solid tumors of the ovary are commonly associated with ascites. 

The abdomen in ascites is filled with clear watery or yellowish 
liquid. Gelatinous masses (coagulated serum) often form in the de- 
pendent parts, as in the pelvis and iliac fossae. Occasionally the liquid 
is quite hemorrhagic; in other cases it is milky from admixture of chyle 
or lymph (chylous ascites). The latter cases are dependent upon ob- 
struction or rupture of the lymphatic channels. In other cases, espe- 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



727 



cially in instances of endothelioma or carcinoma of the peritoneum, the 
liquid has a milky character from admixture of degenerated cells and 
fatty matter. The term chyliform ascites is sometimes applied to such 
cases. Microscopically, the liquid of ordinary ascites shows red and 
white blood-corpuscles and occasionally a few endothelial cells. In 
the hemorrhagic cases the number of blood-corpuscles is notably in- 
creased, while in chylous ascites there are fat-droplets and granular 
cells. 

Occasionally collections of dropsical liquid occur between the layers 
of the omentum (hydrops omenti). 

Ascites causes more or less serious compression and displacement of 
the abdominal organs. The respirations may be greatly embarrassed 
by upward displacement of the diaphragm, and the circulation may be 
obstructed by the pressure of the liquid upon the veins. Secondary 
changes in the peritoneum are not unusual. Long-standing ascites 
nearly always gives rise to a certain amount of chronic inflammation 
(fibrous thickening of the membrane), and terminal tuberculous infec- 
tion of the peritoneum is not infrequent. 

INFLAMMATIONS 

Inflammation of the peritoneum, or peritonitis, is the most im- 
portant condition of this structure. Acute and chronic cases may be 
distinguished. The latter, in most instances, merely represent terminal 
conditions following acute forms of the disease. Exceptionally, peri- 
tionitis may be a chronic affection from the beginning. 

Etiology. — Acute peritonitis is probably always caused by bac- 
teria or bacterial products. It is possible to produce it in animals by 
injections of chemical poisons into the peritoneum, but it is doubtful 
if spontaneous peritonitis over occurs excepting as a result of infection. 

The bacteria gain access to the peritoneum through the blood, by 
direct migration from the Fallopian tubes, by invasion through the walls 
of the abdominal viscera, or by perforation of the viscera or external 
abdominal walls. Hematogenic peritonitis is sometimes met with in 
cases of general septicemia and pyemia, as in osteomyelitis or malignant 
endocarditis, but such cases are rare. In these instances the bacteria 
may be discharged into the peritoneal cavity from the blood, and may 
thus occasion a direct or primary peritonitis; more frequently a localized 
lesion, such as a suppurating infarction, is first produced, and the peri- 
tonitis results secondarily from this. Undoubtedly, bacteria are often set 
free in the peritoneum in the course of infections, but this structure seems 
to have a high degree of resistance, and seems to be possessed of special 
means of defence. The experiments of Pfeiffer with regard to the mech- 
anism of immunity (see p. 279) may be cited in this connection, and 
there are supplied for it two very satisfactory anatomical defenses, 
to wit, the vascular omentum whence many phagocytes may be sum- 
moned and a generous lymphatic drainage through the diaphragm. 
Idiopathic peritonitis was a term used by older authors to designate 
forms of seemingly causeless peritonitis, or such as follow exposure to 
cold and the like. At the present time we must regard these as excep- 
tional instances of primary hematogenic peritonitis or, more commonly, 



728 



A TEXT-BOOK OF PATHOLOGY 



as cases of secondary peritonitis resulting from abdominal infections 
that have been overlooked. 

Peritonitis resulting from direct extension of infective processes is 
very common. A certain amount of irritation of the serous coat (the 
peritoneum) of the abdominal organs occurs in most of the diseases 
of these organs, and in the case of certain infectious diseases this may 
attain considerable intensity. For example, in cases of ulcers of the in- 
testines or strangulation of a coil of intestine with secondary necrosis, 
considerable peritonitis, local and eventually general, may occur with- 
out perforation of the gut. In such cases the bacteria penetrate the 
walls of the intestines along the lymphatic channels, and thus reach the 
serous covering. Similar extensions are found in diseases of the tubes 
and ovaries, or of the uterus in puerperal sepsis. 

Perforative peritonitis is the most important of the forms. It may 
result from perforation of gastric ulcers or cancer, from traumatic or 
ulcerative perforations of other parts of the intestinal tract, from .per- 
foration of the appendix in acute appendicitis, or from rupture of dis- 
eased Fallopian tubes; less commonly perforation of the other abdominal 
viscera, or rupture of infective foci, such as abscesses of the spleen, liver, 
pancreas, ovaries, or other structures, or penetration of the abdomen 
from without by stab-wounds or disease, may lead to peritoneal infection. 

Among the micro-organisms that have been detected, the Strepto- 
coccus pyogenes is most important, and is the cause of the severest forms 
of peritonitis, such as those occurring in puerperal sepsis. Occasionally 
the disease is due to the Staphylococcus pyogenes, the Bacillus coli com- 
munis, the Diplococcus pneumoniae, the bacillus of Friedldnder, the gono- 
coccus, or other organisms. The Bacillus coli is mainly operative in 
peritonitis secondary to intestinal diseases, such as appendicitis. Very 
often, no doubt, peritonitis is the consequence of mixed infection. 

Pathological Anatomy. — Localized and general peritonitis may be 
distinguished. 

Acute localized peritonitis is seen in cases in which bacteria escape 
gradually and in small numbers through the walls of the viscera, or in 
instances in which perforation takes place after exudate has formed a 
wall capable of limiting the extension of the infection. Localized peri- 
tonitis is most frequent in the pelvis in association with diseases of the 
tubes or uterus, and in the region of the appendix. The peritoneum 
in the area of disease first becomes intensely injected (congested), and the 
normal luster disappears in consequence of the beginning exudation and 
disease of the lining endothelium. Subsequently the amount of exudate 
increases. It may, first, be of serous character, but usually is largely 
fibrinous, and the amount may be considerable. Thus, the appendix is 
not rarely surrounded by masses of fibrinous exudate a centimeter or two 
in thickness. The exudate may remain fibrinous, but more frequently 
becomes fibrinopurulent in the later stages; and in cases of perforative 
peritonitis localized abscesses are commonly met with. In such cases 
if the disease remains well encapsulated and the patient survives, the 
exudate may be removed in several ways. Very rarely the pus burrows 
toward the exterior and discharges; more frequently it empties into the 
intestine or some other hollow viscus. It may decrease by gradual 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 



729 



inspissation, leaving a dry, cheesy mass, which in rare instances finally 
becomes calcareous. Fibrinous exudates in localized peritonitis are 
frequently absorbed, and give place to fibrous adhesions. 

Acute general peritonitis may be the immediate result of the dis- 
charge of large quantities of infective matter from a perforated bowel 
or other organ; or it may occur secondarily to a localized peritonitis 
when the limiting wall of exudation is broken down. In these cases 
the peritoneal covering of the intestines, and to a less extent the parietal 
peritoneum, become congested and lusterless, as in the localized form. 
Serous exudation takes place, and may be considerable in amount in 
some of the most violent forms of the disease. Acute inflammatory 
ascites is thus produced. Usually, however, the serous exudation is 
scanty, and very soon the intestines are covered with flakes or thin 
coatings of fibrinous exudate and are matted together. Subsequently 
the exudate grows more yellowish from the emigration of leukocytes or 
pus-cells. When adjacent coils of intestine are agglutinated by the 
exudate, pockets containing serous or seropurulent liquid may be formed 
between them. . 

In the most virulent forms of peritonitis, local or general, such as 
those due to strangulation and gangrene of a part of the bowel, or to 
puerperal sepsis, the exudates may rapidly assume a putrid character, 
and the deposit upon the serous surface, as well as the serosa itself, 
may undergo necrotic change. In these cases the cavity of the perito- 
neum contains more or less ill-smelling brownish, grayish, or blood- 
tinged liquid exudate, and the affected areas of the peritoneum are cov- 
ered with greenish or brownish deposits. 

Hemorrhagic peritonitis is sometimes observed. It represents 
no special form, but merely indicates systemic or local conditions, as a 
result of which hemorrhagic extravasation has taken place into the 
exudate. This is found in the peritonitis of scorbutic individuals or of 
persons reduced in vitality by other diseases. It also occurs when 
passive congestion is associated with peritonitis, as in cases of cirrhosis 
of the liver. The peritonitis accompanying tuberculosis, and especially 
carcinoma of the peritoneum, may .present hemorrhagic exudate. 

Effects of Acute Peritonitis. — 'The disease of the peritoneum has 
an immediate and profound effect upon the intestines, and reflexly 
or in other ways upon the general system. The peristalsis of the bowel 
in the earlier stages is arrested by spasmodic contraction. Very soon 
the musculature is paralyzed and more obstinate constipation results. 
The systemic effects are most strikingly evidenced by the intense shock 
of the early stages. General septicemia may be the consequence of the 
infective conditions of the peritoneum. 

Chronic peritonitis may be the termination of an acute peritonitis, 
especially the localized form. In other cases chronic inflammatory 
thickening occurs in the peritoneum adjacent to or covering organs 
the seat of various diseases. Thus, in cirrhosis of the liver the peritoneal 
covering and the reflexions forming the ligaments may be greatly thick- 
ened, and similarly the peritoneum covering the spleen may be involved 
in consequence of chronic congestion or inflammation of this organ. 
These adhesions may distort organs or act as bands to constrict the 



730 



A TEXT-BOOK OF PATHOLOGY 



intestines, under which circumstances intestinal obstruction may arise. 
When adhesions are numerous, peristalsis is embarrassed and constipa- 
tion is common. 

Chronic peritonitis following local acute peritonitis usually presents 
itself in the form of fibrous thickenings or adhesions, such as are so often 
encountered in the pelvis after uterine, tubal, or ovarian disease com- 
plicated by peritonitis, and about the appendix after inflammations of 
this structure. Less commonly chronic peritonitis is met with in the 
form of sacculated effusions. In such instances the effusion formed dur- 
ing the acute stage is only partially absorbed, and remains as an in- 
spissated liquid. 

In other cases dense adhesions are formed, and occasionally cal- 
careous plates are found in the thickened peritoneal covering of the 
bowels or other parts. The omentum aids in localizing peritonitis, es- 
pecially of the acute exudative forms, and is actively included in the 
chronic stages. It is also a source from which blood and cellular ele- 
ments come into the cavity of the peritoneum, since it is more vascular 
than the rest of the membrane. 

Chronic diffuse peritonitis may result from diffuse acute peritonitis. 
In such cases there are widespread adhesions, and the peritoneum is 
more or less diffusely thickened. Considerable liquid effusion may be 
present. In other instances diffuse peritonitis arises in an insidious 
manner as a chronic process from the beginning. Some of these cases 
are entirely obscure in etiology; in a few it has seemed probable that 
syphilis was an etiological factor. The peritoneum is often uniformly 
thickened, but in some cases presents small nodular lesions, suggesting 
miliary tubercles. In several instances these nodules, together with the 
abundant serous effusion occasionally met with, have led to the diag- 
nosis of tuberculous peritonitis. Microscopical examination of the 
nodules, however, shows a fibrous structure, and neither giant cells 
nor tubercle bacilli. Tuberculous and malignant peritonitis will be 
considered below. 

Hyperplastic Perihepatitis. — A few cases have been observed of a 
remarkable disease in which the upper part of the parietal peritoneum 
and the reflexions covering the liver and spleen are greatly thickened 
and of dense sclerotic character — hyaloserositis. The peritoneum is 
sometimes several millimeters in thickness, gray or white, and suggests 
the appearance of the " icing" of confectioners. This has led to the 
term proposed by Curschmann — Zuckergussleber. The liver and spleen 
undergo more or less pressure-atrophy, and ascites is a frequent symp- 
tom. The etiology is obscure. 

INFECTIOUS DISEASES 

Tuberculosis may in rare instances affect the peritoneum primarily, 
as in cases in which tubercle bacilli penetrate the mucosa of the intes- 
tines and enter the lymphatics without causing an intestinal lesion; 
or in cases of infection through the Fallopian tubes. Usually tubercu- 
losis of the peritoneum is secondary to tuberculosis of some abdominal 
viscus or of more distant organs. Thus, among the more frequent causes 
are tuberculosis of the mesenteric or retroperitoneal glands and tubercu- 



PLATE i 5 



1 



Tuberculous ulceration in intestine showing miliary and infiltrative lesions beneath 
peritoneum and in mesentery. 



DISEASES OF THE G ASTRO-INTESTINAL TRACT 731 

lous disease of the tubes and ovaries in women. Intestinal tuberculosis 
rarely leads to more than localized lesions of the serous coat opposite 
the ulcerations of the mucosa. Pulmonary tuberculosis may occasion 
hematogenic infection of the peritoneum. Simultaneous tuberculosis of 
various serous membranes, especially the pleura and peritoneum, is 
occasionally observed. The source of infection is often hidden; some- 
times the pleura is first involved and the peritoneum becomes affected by 
extension; less commonly the reverse o 'curs. 

Pathological Anatomy. — Miliary tuberculosis without marked in- 
flammatory changes may occur as a generalized peritoneal affection 




Fig. 350. — disseminated miliary tuberculosis of peritoneum with caseous glands in the 

mesenteric stalk. 

in acute or subacute general miliary tuberculosis. Local eruptions of 
similar character are seen in the pelvic peritoneum in cases of tubal or 
ovarian tuberculosis and upon the serosa of the intestines adjacent to 
tuberculous ulcers of the bowel (Plate 15). 

More important, from a clinical point of view, are the cases in which 
inflammatory changes are associated with the specific tubercle. In 
some instances unaccompanied by a fluid exudate extensive adhesions 
by fibrinous or fibrous productions are met with, while the tubercles 
tend to agglutinate, forming masses of considerable size and of cheesy 
character. The mesenteric lumph-glands may be coincidently involved, 
being enlarged and caseous. Sacculated collections of serous or sero- 
purulent liquid are sometimes observed. In another variety there is 
abundant serous exudation. Occasionally the exudate is hemorrhagic. 



732 



A TEXT-BOOK OF PATHOLOGY 



Tuberculosis of the peritoneum sometimes terminates in complete 
resolution, the peritoneum being left somewhat thickened, but showing 
no other evidences of the previous disease. Such a result may at times 
be obtained by simple laparotomy and drainage. In other cases the 
active general inflammatory and adhesive character of the lesion may 
cease but a local caseous nodule may remain, sufficiently active to 
ulcerate through the intestinal wall with the production of local abscesses 
and infiltrations of the submucosa or ulcers upon the mucosa. 

TUMORS 

Fibromata and lipomata are sometimes met with as small nodular 
or pedunculated outgrowths from the subperitoneal tissues. The latter 
usually emanate from the omentum or epiploic appendages and may 
reach considerable size. Their significance is threefold: they may so 
disturb intestinal function as to interfere with digestion, they may 
incapacitate sufficiently hy bulk to demand operation and they may 
weaken the abdominal openings so that hernia is favored. 

Sarcoma proper is a rare primary tumor and usually starts in sub- 
peritoneal lymphatic or areolar tissue. Secondarily such tumors occur 
but not commonly on the peritoneum proper. 

Carcinoma of epithelial origin does not occur on the peritoneum 
primarily, although secondarily this tissue is frequently the seat of 
thickly seeded miliary nodules like tubercles, especially in the diaphrag- 
matic area, carcinomatosis, and of directly implanted new growths. 
In the latter cases, spread from original growths in the abdominal vis- 
cera leads to diffuse fibrous thickening and tumors, to local nodular 
pearly masses, or to pseudomyxoma peritonei. The last mentioned 
lesion is usually described as originating from ovarian cysts and tumors 
but analogous formations have been seen after several kinds of ab- 
dominal tumors. Its characters lie in the appearance of masses of 
gelatinous matter, provided with no retaining wall, scattered over a 
thickened peritoneum and accompanied by ascites. When this has 
arisen from a true tumor, an attempt is made to reproduce the neoplasm 
along with this pseudomucinous mass, while after ovarian cysts, nothing 
but the gelatinous material is found. 

In the diffuse form mentioned above, inflammatory changes with 
intestinal agglutination and adhesion are frequent. Hemorrhagic 
exudation is not unusual. In rare cases the bowels are so firmly fused 
by the spreading tumor and the inflammatory exudates that they form 
a solid mass, which on section shows the cavities of adjacent coils of 
intestines separated by more or less uniform tumor tissue. 

Endothelioma or mesothelioma of the peritoneum is sometimes 
called carcinoma or sarcoma and, truth to tell, its exact classification is 
not settled. Whether it arises from the subendothelial lymph channels 
or from the flat superficial cells is uncertain and there seems no settle- 
ment to be hoped for from its gross appearance or clinical behavior. 
It forms a diffuse firm white thickening of the membrane, sometimes 
with coarse nodulations, which surrounds and binds down the viscera; 
ascites is usually present. The growth spreads sluggishly but may 



DISEASES OF THE GASTRO-INTESTINAL TRACT 



733 



penetrate the organs or the diaphragm. Secondary growths appear 
usually in lymph nodes and the lungs. 

Lymphocysts are occasionally found beneath the peritoneal surface 
and in the mesenteries. Chylous cysts are sometimes encountered 
at the root of the mesentery when the central stalk glands are fibrotic, 
or letroperitoneally situated when the thoracic duct is obstructed. 

PARASITES 

Echinococcus cysts occasionally occupy the peritoneal cavity, and 
may fill it almost completely. Filaria have been found in a few instances ; 
and the Linguatula rhinaria and Cysticercus cellulosce have been reported. 
An ameboid organism (Leydenia gemmipara) has been discovered in 
the liquid exudate of certain cases of ascites. 



CHAPTER VI 



DISEASES OF THE DUCTLESS GLANDS 

Physiologic Considerations. — The term Ductless Glands is appro- 
priate to the organs that will be discussed in this chapter but in a larger 
sense is inappropriate as certain other glands (pancreas, testis, ovary), pro- 
vided with ducts for the discharge of their external secretions, share with 
ductless glands the function of elaborating internal secretions which are 
poured into the blood. The term endocrine glands has in recent years 
come into common use and is advisable as it applies properly to all 
glands (ductless or otherwise) which elaborate internal secretions having 
specific relations to growth and metabolism. The internal secretion 
elaborated in the glands is transported in the blood and acts upon the 
cells of the body generally or upon other organs, stimulating or inhibiting 
them. The term hormone is used to designate such specific secretions 
that act upon other organs, though its applicability is no longer quite 
justified since we have learned that the secretions sometimes inhibit 
the function of other glands, whereas the name hormone indicates a 
substance that stimulates or activates. 

While there can be no doubt of the interrelation of the endocrine 
glands and their power to stimulate or inhibit one another, the whole 
subject is still too much confused by its complexity and the want of 
accurate knowledge to justify representation in the form of geometric 
schemata indicating the directions and quality of action of one gland 
upon another. 

The relationship of the endocrine glands and the nervous system 
(autonomic and sympathetic systems) while undoubted is still very 
obscure. That some of the secretions exercise their effects through the 
nervous system and that the latter may in turn influence the glands 
seems certain. To what extent the sympathetic and autonomic 
systems may influence growth or nutrition directly (without intervention 
of endocrine glands) is uncertain, but investigations regarding so-called 
trophic nerve fibers seem to show the existence of such direct action. 

Some of the endocrine glands seem to be related mainly to growth 
and development after which their function ceases and (notably thymus) 
the gland may atrophy ; others may be related to growth and development 
and to certain physiologic functions that pertain to only a portion of 
the life history (sex-glands), while others remain active throughout 
life (pancreas, adrenal). It must be added that most if not all of the 
endocrine glands seem to have more than a single function and that 
while their function in one direction may no longer be required, their 
activity in other directions may still be needed. Thus the hypophysis 
has undoubted relations to bony growth (probably a temporary function) 
while other activities continue through life. 

734 



DISEASES OF THE* DUCTLESS GLANDS 



735 



The Thyroid Gland 

Anatomical Considerations. — The thyroid gland is a compound 
tubular gland, which in fetal life communicates with the pharynx at the 
base of the tongue by a duct. Later the duct is obliterated, and the 
gland becomes ductless. Microscopically, there are found acini lined 
with polyhedral or cylindrical epithelium, usually in a single layer. 
The lumen of the acinus contains more or less gelatinous or, as it is 
usually called, colloid material, which seems to be a secretion of the 
epithelium. It is composed of nucleoprotein and globulin, the latter, 
the thyreoglobulin, containing a notable proportion of iodin. Kendall 
has isolated a crystallizable substance which doubtless represents 
the iodin-containing "active principle" and has given it the name thyroxin. 
The vascular supply of the gland is very abundant, the blood-vessels 
being numerous and the anastomoses very free. The lymphatic net- 
work is equally abundant, and mainly situated in the stroma of the 
gland around the acini. The larger lymphatics are supplied with 
valves like those of the veins. Occasionally colloid material has been 
found in the stroma and in the lymphatics. The capsule of the gland 
is a fibrous covering from which trabecule extend into the substance of 
the organ. 

CONGENITAL DEFECTS 

Occasionally one or another part of the gland is wanting, or, in rare 
instances, the entire organ. 

Accessory thyroid glands have been found in various situations. 
Sometimes small masses of thyroid tissue occur alongside of a normal 
gland, either above it, in the neck, or below it, behind the sternum and 
in the anterior mediastinum. In other cases the normal thyroid is ab- 
sent, but is represented by small masses in the situations named or in 
other parts. In a few instances tumors at the base of the tongue and 
within the larynx and trachea have been found to be composed of thyroid 
tissue, or the thyroglossal duct remains partly patulous and cyst-like 
swellings arise. 

DISTURBANCES OF CIRCULATION 

Hyperemia of the thyroid gland is met with very frequently. It 
occurs in cases of cardiac failure, and in consequence of obstruction 
of the large veins by mediastinal tumors and the like. In these in- 
stances the thyroid may be considerably enlarged, and has a soft, doughy 
character. Slight enlargement of the thyroid is found in perhaps a 
majority of the cases of chlorosis, and may be present in any form of 
anemia and during pregnancy and menstruation. This enlargement is 
doubtless to a large extent the result of congestion, and may be attended 
by a certain amount of increase in thyroid function. In Graves ' disease 
the thyroid may be very vascular, and the enlargement of the gland may 
be in large part due to dilatation of the blood-vessels (see below) . 



736 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATIONS 

Acute thyroiditis may occur in the course of various infectious 
diseases, notably typhoid fever. Occasionally it arises without definite 
preceding disease. The gland enlarges and becomes rather tense. The 
termination is usually in resolution, and this may occur very rapidly 
suggesting that the enlargement of the gland is due largely to con- 
gestion and liquid exudation, rather than to cellular (inflammatory) 
infiltration. 

Acute suppurative thyroiditis, or abscess, occurs in consequence 
of embolism, in cases of infected wounds, endocarditis, or general pye- 
mia. Sometimes the inflammation extends directly from local diseases, 
such as diphtheria. The abscess may rupture, or may undergo secondary 
changes — inspissation, calcification. 

STRUMA OR GOITER 

Definition. — Goiter is the name applied to various enlargements 
of the thyroid gland. It is a clinical rather than a pathological term. 
Sometimes a distinction is made between benign and malignant struma, 
the latter term including definite tumors of the thyroid gland. At the 
present time the term " goiter" is restricted to enlargements of a hyper- 
plastic character, which, though often resembling tumors, cannot be 
definitely classified among the tumors of the gland. 

Etiology. — Goiter occurs endemically in certain situations, as in 
Switzerland and other parts of Europe, and in various sections of this 
country. Sporadically, it is met with in all parts of the world. Local 
conditions of some kind are doubtless among the fundamental causes, 
but the nature of these conditions is but little known. The drinking- 
water has always been suspected, and it seems likely that it has some 
influence, though it is certain that the magnesium and calcium salts 
have not the importance formerly ascribed to them. Infectious causes 
have been suspected and micro-organisms have actually been described, 
but no satisfactory demonstrations have been made. 

Pathological Anatomy. — The thyroid gland may be uniformly 
or irregularly enlarged. In most instances both lobes and the isthmus 
are involved but enlargement of one lobe alone or irregular, more or 
less nodular, swellings may be met with; not infrequently substernal 
goiter is discoverable by clinical or a>ray examinations. These sub- 
sternal masses may be extensions from the gland above or may be hyper- 
plastic adventitious thyroid glands. Very rarely ectopic thyroid tissue 
in other situations (for example, at the root of the tongue) may be in- 
volved. The size of goiters may be little above that of the normal gland, 
or may reach enormous proportions when great disfigurement of the neck 
results and marked pressure effects may be produced. The largest goiters 
are likely to prove of the cystic variety. Two principal varieties may 
be distinguished: the parenchymatous and the vascular. 

Parenchymatous goiter is a variety in which the glandular tissues or 
acini undergo more or less active hyperplasia. The gland is generally 
uniformly enlarged, but sometimes presents lobular or nodular eleva- 
tions. The tissue is ordinarily somewhat elastic, like that of the normal 
thyroid, but may in other instances be very firm. Occasionally cystic 



DISEASES OF THE DUCTLESS GLANDS 



737 



forms occur, and a subvariety is sometimes distinguished by the term 
cystic goiter. 

Microscopically, there may be found merely a uniform hyperplasia 
of the glandular acini, without any notable change in the structure of 
the tissue. The hyperplasia may in other cases be so great as to simulate 
papillary cystadenoma (see Fig. 353). In most instances the acini 
contain but small quantities of colloid material, as is the case in the 
normal gland. Sometimes, however, there is abundant production of 
colloid, and the acini are greatly distended; the term colloid goiter may 




Fig. 351. — Colloid goiter, showing colloid material in the dilated acini. 



be applied in such instances (Fig. 351). In certain cases the walls of 
the acini are destroyed and the colloid of adjacent acini runs together, 
forming considerable cysts. In these instances the thyroid consists of 
numerous cystic excavations. Changes in the interstitial connective 
tissue of the gland may be comparatively slight, but may in other cases 
become conspicuous. The capsale of the gland may be thickened 
and the stroma may predominate over the glandular elements. The 
term fibrous goiter has been suggested for such cases. 

Vascular Goiter. — This term is applied to enlargements of the thyroid 
gland characterized by marked dilatation of blood-vessels within the 
organ. The glandular tissues themselves present changes similar 
to those described under, parenchymatous goiter. The gland undergoes 
considerable and sometimes enormous enlargement, and may pulsate 

47 



738 



A TEXT-BOOK OF PATHOLOGY 



actively. This form of goiter is met with as the important pathological 
condition of many cases of Graves' disease (see p. 743). 

The alveoli vary greatly in size and form, often sending out diver- 
ticula which become constricted off to form new alveoli (Fig. 352). 
The epithelium is at first hyperplastic, then becomes natter as the col- 
loid increases in amount and density. The vascular supply is unusually 
rich, the veins especially being large and distended with blood, their 
walls being very friable. They lie, for the most part, in the increased 
connective-tissue framework, in which tissue are also numerous small, 




Fig. 352. — Parenchymatous and vascular goiter, showing large, thick-walled blood-vessels. 

circumscribed, scattered lymphoid nodules. Corresponding with this 
there may be an enlargement of the cervical lymph-glands and of the 
thymus. 

The parathyroid glands show a moderate atrophy of cells and in- 
duration or increase of connective tissue, but this is by no means con- 
stant or sufficiently extensive to support the idea that these glands are 
in any way the cause of the disease. 

There is also recognized a form of goiter in which hyperplasia, in- 
stead of being diffuse as in the two preceding types, is of a nodular 
character. In this case areas of active hyperplasia are mixed with 
normal or atrophic fields. To these cases the name adenomatous goiter 
is given. If, however, the lobular and acinus grouping should revert 
to the fetal character, the name fetal adenoma is given (Fig. 354). It 



DISEASES OF THE DUCTLESS GLANDS 



739 




Fig. 353. — Papillary cyst adenomatous hyperplasia of thyroid gland. 




Fig. 354. — Fetal adenoma of thyroid, 



740 



A. TEXT-BOOK OF PATHOLOGY 



must be emphasized that these are not tumors, as their names would 
imply, but hyperplasias of insular character whose causation is not 
understood. They are actively proliferative forms, especially the latter, 
but may or may not give symptoms. 

Relation of Histological Change to Clinical Conditions. — 'The function 
of the thyroid cells seems to be to form colloid and elaborate an internal 
secretion, the latter seemingly closely bound with the former. The 
resting gland has low cuboidal or thick flat cells, a moderate amount of 
colloid, little interstitial cellular tissue and moderate vascularity. In 
the process of hyperplasia there is first congestion, then increase in the 
size of the epithelium and reduction of colloid, for, with greater blood-sup- 
ply, more absorption takes place. This, in any one of the anatomical 
forms of hyperplasia mentioned above, supplies the basis for hyperthy- 
roidism. As the vascularity and, usually, interstitial cellular infiltrate 
increase, low-grade inflammatory changes may take place and a stage of 
retrogression set in. This is marked by a lower stature of the epithelium 
firm colloid and fibrous tissue increase. There is less absorption at this 
stage, and it represents a condition possible in simple goiter. A return 
of hyperplasia in such an atrophic gland may again lead to toxic symp- 
toms. It seems that the absorption of colloid is responsible for hyper- 
thyroidism. The iodin content of fully formed colloid in normal or 
regressive thyroids is high, while that of the mucoid material replacing 
colloid in hyperplastic glands is low. What disturbs the balance and 
induces the hyperplasia is not known. 

Secondary Changes. — The hyperplasia of connective tissue between 
the acini has been referred to. Sometimes this becomes so considerable 
that the term "fibrous goiter" is warranted. Cystic formations have 
also been mentioned, the cysts referred to resulting from the confluence 
of the dilated acini. The contents in such cases consist of colloid material 
or of more or less serous or hemorrhagic liquid. Occasionally cysts result 
from hemorrhage in degenerated parts of the gland, with subsequent 
absorption of the blood and exudation of serous liquid. The contents 
in such cases may be purely serous or may consist of brownish grumous 
matter containing abundant cholesterol. Very rarely secondary pro- 
liferative changes occur in the walls of the cyst, causing papillomatous 
projections. Calcification is a very common terminal change in degen- 
erated goiters. It may occur in isolated areas or may cause a uniform 
hardening of the gland.. Actual ossification has been observed. In- 
flammation of a goitrous thyroid is known as strumitis, to distinguish it 
from thyroiditis. 

Mechanical Effects of Goiter. — The enlarged gland presses upon 
the adjacent structures more or less seriously. The trachea is most 
frequently compressed or dislocated from its median position. Pressure 
upon the large veins may occasion passive congestion and edema; and 
less commonly pressure on the carotid artery may interfere with the cir- 
culation of blood in the brain. The nerves in the vicinity (vagus, 
recurrent laryngeal, and sympathetic) are likewise exposed to pressure. 

Substernal goiters are particularly disposed to occasion pressure effects. 
INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary tubercles or as small 
caseous nodules. 



DISEASES OF THE DUCTLESS GLANDS 



741 



Syphilis is met with in the form of gummata. 
Actinomycosis is a very rare disease of the thyroid gland. 

TUMORS AND PARASITES 

Tumors. — The term " malignant struma" is sometimes applied to 
tumors, and it is difficult in certain cases to draw a sharp line between 
certain goiters and distinct new growths (adenomata) . 

All tumors of the thyroid have a tendency to cystic change and, as 
might be expected of this organ, to collections of colloid. These charac- 
teristics persist in mestastases. 

The term adenoma, however, should be restricted to cases in which 
the proliferation of acini is atypical, and in which the tumor is circum- 
scribed, nodular, or otherwise distinguishable from the pre-existing 
gland tissue. Sometimes tumors of the thyroid having typically adeno- 
matous characters give metastasis. The tumors are prone to assume 
cystic and papillomatous change. 

Carcinoma may occur in the form of a nodular or more diffuse tumor. 
Metastasis is frequent in cases of carcinoma, but also occurs in cases that 
present the appearances of an ordinary adenoma. The bones are fre- 
quently involved by metastatic deposits. Extension from the thyroid 
to the adjacent organs is not infrequent. Carcinoma sarcomatodes has 
been described several times. 

Sarcoma occurs in several varieties. Round-celled sarcoma and 
angiosarcoma are particularly malignant. 

Secondary tumors in the thyroid are rare. 

Parasites. — Echinococcus cysts have been met with, but are very 
rare. 

GENERAL RESULTS OF THYROID DISEASE 

The physiology of the gland has not as yet been fully determined, 
though certain facts have become established. The old authors be- 
lieved the gland to be active as a blood-making organ, and this is still 
maintained by some. It is, however, unlikely that this function is an 
important one. The frequent association of thyroid disease with certain 
general conditions (cretinism and myxedema) has led to experiments 
upon animals that have established certain important facts. 

In earlier experiments at removal of the thyroid gland in animals 
various nervous symptoms resembling those of tetany were noted. 
Later investigations have shown that these results were due to the 
simultaneous removal of the parathyroid bodies. In more recent 
studies care has been taken to avoid this parathyroid ablation, and it 
has been found that in young animals checking of ossification and stunt- 
ing of growth, enlargement of the hypophysis, apathy, and other symp- 
toms suggestive of cretinism in man occur. In adult animals a con- 
dition closely simulating myxedema in man occurs, and the term cachexia 
strumipriva has been applied to it. This is characterized by pallor, 
edema of the skin, general weakness, loss of hair, and alteration of the 
cerebral functions (intellection, sensation, and motor power) . 

Removal of the thyroid causes a decrease in protein metabolism and 
an increased tolerance of carbohydrates. The latter effect seems to be 



742 A TEXT-BOOK OF PATHOLOGY 

due to an action of the thyroid antagonistic to that of the pancreas which 
checks the mobilization of sugar, while the thyroid facilitates it. The 
relationship of the thyroid to carbohydrate metabolism is further in- 
dicated by the frequency of glycosuria in cases of goiter attended with 
evidences of increased thyroid function. 

Marked increase in metabolic activity may be produced by feeding 
dessicated thyroid gland and is a regular occurrence in cases of hyper- 
thyroidism to such an extent that the determination of the basal met- 
abolism has become a useful clinical method for diagnosis and prognosis. 

Cretinism is a peculiar disease, occurring with great frequency in 
certain parts of central Europe, especially in Switzerland, and not infre- 
quently in other parts of the world. The 
thyroid gland is sometimes atrophic and 
sometimes goiterous, but in all cases 
diseased. The disease is not, as a rule, 
present at birth, but usually develops soon 
thereafter; the parents may be cretinoid 
or goiterous, though sometimes healthy 
parents have cretin children. The cretin 
remains physically and mentally unde- 
veloped; the subcutaneous tissue is flabby, 
abundant, and sometimes distinctly myxe- 
dematous (Fig. 355); the head is large; the 
lips and tongue thickened, and the latter 
often protrudes from the mouth; the hairs 
of the body are little developed. Lack of 
bony development and incomplete ossifica- 
tion occasion the stunted and often de- 
formed condition of the cretin. 

A distinction must be made between 
sporadic and endemic cretinism. In the 
latter the appearances are much less uni- 
form and the mental retardation com- 
paratively more marked than the physical 

Y IG . 355. Cretin. evidences of cretinism. 

Myxedema is a disease that develops 
in later life, sometimes after distinct diseases of the thyroid (goiter, 
gumma, tumors, etc.), but often without any manifest disease of thyroid, 
though atrophy and degenerations (calcification) may be disclosed by 
the postmortem examination. 

There is a peculiar swelling of the eyelids and of the subcutaneous 
tissue of the face and neck, and subsequently the same change occurs 
elsewhere, involving the limbs and the entire body. The appearances 
at first suggest edema, but there is not the usual pitting on pressure, 
and the feeling conveyed to the hand is that of an infiltration with some 
form of gelatinous tissue. This has been-found to consist of a mucin- 
like substance, often associated with increase of the adipose tissue 
itself. The skin of the patient is pallid and exceedingly dry; the hair 
falls out, and nervous symptoms are developed. Eventually, intellec- 
tion may be almost destroyed. 




DISEASES OF THE DUCTLESS GLANDS 



743 



The resemblance of these diseases to the symptoms produced by 
operative removal of the thyroid gland makes it certain that disease 
of the thyroid is the fundamental condition in cretinism and myxedema. 
This fact is still more clearly demonstrated by the numerous cures of 
these diseases following implantation of sheeps' thyroids in the perito- 
neal cavity, and especially the feeding of thyroid-gland tissue or extracts. 

Graves' disease has been referred to in connection with goiter. 
The cardinal symptoms of this disease are enlargment of the gland, 
palpitation of the heart, exophthalmos, and muscular weakness and 
tremor. The pathology of the di- 
sease has not as yet been fully 
determined. It seems likely, how- 
ever, from recent investigations 
that the thyroid disease, from 
whatever cause it may result, is 
the primary disorder. Removal 
of large parts of the gland has 
been found to control the symp- 
toms of Graves' disease in a large 
number of cases, and the feeding of 
thyroid glands for a long period 
of time produces symptoms like 
those of Graves' disease: rapid 
action and palpitation of the 
heart, exophthalmos, and tremor. 
According to the view here ex- 
pressed, the symptoms which to- 
gether constitute Graves' disease 
are probably due to overproduction 
of thyroid secretion; they are, in 
fact, the result of hyperthyroidism. 
The symptoms, pathological his- 
tology, Chemical Studies, and results Fig. 3o6.-The thyroid gland and para- 
of surgical treatment all seem to thyroid glandules; blood-supply (posterior 

indicate that the pathogenesis of view ) (Haisted and Evans). 
Graves' disease is explainable as 

a state of hyperthyroidism. Some authors, however, have insisted that 
the thyroid enlargement is compensatory, that is, indicative of an 
attempt to correct diseased conditions originating elsewhere by increased 
thyroid activity. An older theory regarding the nature of the disease 
attributed it to a primary derangement in the sympathetic nervous 
system. 

Occasionally cases of otherwise typical Graves' disease without 
thyroid enlargement may be met with. This, however, does not prove 
that the gland is histologically or functionally normal. 

Occasional instances of association of Graves' disease and myxedema 
in the same patient have been reported by competent observers. Their 
interpretation is somewhat difficult if Graves' disease is due entirely to 
hyperthyroidism. M 




744 



A TEXT-BOOK OF PATHOLOGY 



Parathyroid Glands 

The parathyroid glands are small bodies, usually four in number, 
lying posterior to the thyroid gland and on or within its capsule, consist- 
ing of closely packed acini similar in cellular appearance to the larger 
gland in its fetal stage. Their relation to the thyroids and general met- 
abolism is not clearly understood. Their complete removal causes tetany, 
and this disease, whether it occurs in association with gastric diseases, 
infections, pregnancy or parturition, or in childhood or certain occu- 
pational relationships, is regarded as essentially a hypo-thyreosis. That 
the parathyroids have some importance in the calcium metabolism has 
been shown in experimental investigations as well as in cases of tetany, 
and that this metabolic fault stands in some relation to tetany is in- 
dicated by a disappearance of the signs thereof upon the introduction 
of calcium salts. In some way these glands seem to be related to the 
deposit of calcium salts in bone. The parathyroids are sometimes the 
seat of hyperplasia or true tumors. 

The Suprarenal Bodies 

Anatomical Considerations. — The suprarenal bodies are com- 
posed of a cortical and a medullary portion, and are enclosed in a fibrous 
capsule from which septa extend into the substance of the organ. The 
cortical portion (interrenal tissue) is of mesothelial origin and closely rel- 
ated in derivation to the sex glands. The chief cells resemble closely the 
interstitial cells of the testis and the cells of the corpora lutea of the ovary. 
The medulla has as its chief constituent cells derived from the neuroblasts 
of the central nervous system. The cortical portion is composed of col- 
umns of polygonal cells filled with double refractive granules of lipoid 
substance. Three layers are distinguishable in the cortex: an outer 
zone, in which the cells are arranged in oval masses (zona glomerulosa) ; 
a middle zone, in which they form cylindrical columns extending toward 
the medulla (zona fasciculata) ; and an inner zone, composed of irregularly 
anastomosing columns of cells (zona reticularis). The cells of the middle 
zone are the most markedly granular. The medulla of the gland consists 
of similar polygonal cells arranged in cords or ii regularly anastomosing 
columns, and contains numerous non-medullated nerve-fibers and multi- 
polar nerve-cells, as well as aggregations of cells which are stained brown 
by chromic acid (chromaffin cells). These cells are derived from the 
neuroblasts of the central nervous system and are found distributed in 
various situations as a " chromaffin system." Among these situations 
are the sympathetic nerves, the root of carotid arteries (carotid gland), 
the left coronary, the superior mesenteric, the solar plexus, etc. In all 
these situations the chromaffin cells doubtless have the same functional 
action — manufacture of adrenalin or epinephrin — as in the suprarenal 
bodies. 

Physiological Functions. — The important function of the supra- ■ 
renal gland, thus far determined, is the manufacture of epinephrin by the 
chromaffin cells. This substance has the general effect of stimulating the 
peripheral ends of the nerves of the true sympathetic system, owing to 
which it causes marked rise of blood-pressure. Probably the same action 



DISEASES OF THE DUCTLESS GLANDS 



745 



accounts for the occurrence of glycosuria following injection of epi- 
nephrine the action in this case being upon sympathetic nerve-fibers in 
the liver. This and other evidence indicates that the suprarenal glands 
are closely related to carbohydrate metabolism. It is believed that epi- 
nephrin is diminished in nervous strain, fatigue, injury with shock, and 
bacterial diseases. While it is supposed to be increased in conditions 
with high blood-pressure, there is no direct proof that this secretion is 
high in any disease. 

The functions of the cortical cells is less definitely determined. 
That they stand in same sort of relationship to the sex-glands is evident 
♦ from their embryological derivation as well as from the occurrence of 
premature sex-development, menstrual disorders and pseudoherma- 
phroditism in cases of tumors of the suprarenal cortex or of ectopic 
suprarenal cortex "rests" (hypernephromata) . 

The occurrence of pigmentation in Addison's disease suggests a re- 
lationship of the suprarenal glands to the pigment production, but the 
pathogenesis is not as yet clearly determined. 

CONGENITAL ANOMALIES 

Accessory suprarenal bodies may be found in the vicinity of the 
main body. Of peculiar interest are the portions of suprarenal tissue 
(cortical cells) found in the capsule or cortex of the kidney. These "rests" 
may subsequently proliferate and form tumors of the kidney. (See 
Tumors of the Kidney.) 

Occasionally the suprarenal bodies are found in unusual situations. 

Malformations of the adrenal system seem to be connected with 
structural abnormalities in the nervous and genital organs. 

DEGENERATIONS 

Fatty degeneration is normal in adults. It affects the cortex, giving 
this layer a yellowish color. The substance of the cortex may separate 
through the middle zone, forming a cavity suggesting a cyst. This is 
probably in part a postmortem production. 

Pigmentation is observed in the cells of the medullary portion, 
especially in persons of advanced age. 

Amyloid infiltration occurs in connection with amyloid disease of 
other organs. The suprarenal body becomes hard and of a grayish, 
translucent appearance. The degeneration affects the walls of the 
blood-vessels, from which it extends to the connective tissue. The 
glandular portions suffer pressure-atrophy. The cortex is more fre- 
quently involved than the medulla. 

INFECTIOUS DISEASES 

Tuberculosis of the suprarenal body is the most important of its 
diseases. Miliary tubercles may be met with in cases of general tuber- 
culosis, but a fibrocaseous form of the disease is more frequent and of 
much greater significance. The gland is enlarged, sometimes reaching the 
size of an egg; it is hard and usually rather nodular or irregular in out- 
line. The capsule is thickened, and the substance of the gland is com- 
posed of dry, yellowish, cheesy matter, or of a puriform material. 



746 



A TEXT-BOOK OF PATHOLOGY 



In the later stages the caseous or puriform matter may be inspis- 
sated, and fibrous-tissue growth may convert the entire body into 
a shrivelled, hard mass of connective tissue. Sometimes one gland 
alone is involved; more frequently the disease occurs bilaterally. Tuber- 
culosis of this form may be primary, but usually is secondary to tuber- 
culosis of the lungs, intestines, or other organs. 

Addison's disease, in which fibrocaseous tuberculosis of the supra- 
renal bodies is commonly present, is an affection characterized by 
brownish pigmentation of the skin of exposed parts of the body (face, 
neck, and hands), and of the skin in the flexures of the joints or in other 
parts subjected to pressure. The pigmentation usually occurs in a 
mottled form at first, but soon becomes uniform. Brownish or purplish 
spots upon the mucous membranes (mouth) are not unusual. Besides 
pigmentation the characteristic symptoms are great weakness, disturb- 
ances of the stomach (vomiting), and cardiovascular asthenia. 

Though fibrocaseous tuberculosis of the suprarenal gland is dis- 
covered in many cases, Addison's disease may occur in association 
with other affections of the suprarenal, such as tumors; and it may be 
absent despite the existence of tuberculosis or of other diseases of both 
of the glands. The absence of Addison's disease in the latter cases has 
been explained by some writers by the assumption that the suprarenal 
disease had not existed long enough for the development of the symp- 
toms of Addison's disease. Occasionally, alterations in the sympa- 
thetic nervous system (semilunar ganglia and solar plexus) have been 
discovered when the suprarenal glands were apparently normal. No 
explanation of such cases can be made. It must be accepted at the 
present time that the suprarenal bodies are in some way concerned 
in the etiology of the disease, but it is impossible to state how much dis- 
ease of the cortex and medulla (chromaffin system) respectively are 
concerned. It seems evident that the medulla is largely involved 
(low blood pressure, asthenia, etc.), and disease of the chromaffin system 
outside the adrenals may explain the cases of Addison's disease without 
lesions of these glands. 

Lewin found among 281 cases — typical cases of Addison's disease 
with sound adrenals, 20 per cent.; typical cases of Addison's disease with 
diseased adrenals, 80 per cent.; disease of adrenals without bronzing, 
28 per cent.; disease of adrenals with bronzing, 72 per cent. In Addi- 
son's original paper he included 3 cases of secondary cancer of the adrenals 

Tumors and hyperplasia of the adrenal cortex in the young female 
lead to early puberty and a certain degree of masculinity, and in the 
male to general sexual precocity. 

Syphilis occurs in the form of gummata. Uniform fatty degenera- 
tion of the suprarenal body has been met with in congenital syphilis. 

CIRCULATORY DISTURBANCES 

Hemorrhage is comparatively rare. It may occur in association 
with hemorrhagic diseases or severe anemias, especially leukemia. 
Sometimes it is caused by traumatism or by obstruction of the venous 
circulation. The hemorrhage may be inconsiderable or may be quite 
large. In the latter instances secondary rupture of the hematoma may 



DISEASES OF THE DUCTLESS GLANDS 



747 



cause death by intraperitoneal hemorrhage or a hemorrhagic cyst may 
result. Profound asthenia and rapid death may result from hemorrhage 
into the suprarenal glands. 

INFLAMMATION 

Inflammation of the suprarenal body is very rare. A simple and 
a hemorrhagic form have, however, been described. Abscess may 
occur in consequence of pyemia, or as a secondary condition following 
other forms of suprarenal disease. 

TUMORS 

Sarcoma is the most frequent form of tumor. Melanotic as well as 
unpigmented varieties are met with. The tumor may reach consider- 
able size, and may destroy the gland completely. 

Adenoma may arise from the cells of the acini. Histologically, these 
tumors resemble the fascicular zone of the cortex, from which they 
doubtless arise in the great majority of cases. The tumor occurs 
as a nodular, irregular growth, often of a yellowish or brownish color. 
"Lipomatous struma of the suprarenal" is a name given by Virchow to 
a fatty nodular tumor growing from the cortex. 

Hypernephroma may occur as a primary tumor in the suprarenal, 
and when found in the young is almost always associated with ab- 
normalities of the sexual characters. In the cases of hypernephroma of 
the kidneys these conditions are usually lacking. 

Tumors of the cortex of the kidney, having the structure of supra- 
renal tissue, are described under Tumors of the Kidneys. 

Qliomata have been described, but it is doubtful whether these 
tumors are true gliomata. 

Neuroma is a rare form of suprarenal tumor, arising from the 
neural tissue in the medulla. (See section on tumors of nervous tissue.) 

Secondary sarcoma and carcinoma are not infrequent. 

The ThymUvS Gland 

Anatomy and Development. — The thymus gland at its earliest 
period consists of entodermic epithelium arranged somewhat like that 
of an epithelial gland. The thymus gland is derived from the branchial 
clefts and is therefore essentially an epithelial structure but when fully 
developed contains in the spaces between the epithelial ground work 
masses of cells resembling lymphocytes. Some anatomists insist that 
these cells are of epithelial origin but others maintain the correctness 
of the older view that they are lymphoid cells. Here and there in the 
center of these may be seen concentric whorls (the corpuscles of Hassall), 
the remains of the original epithelial cells. After the second year of 
life retrogressive changes take place, and by the age of adolescence the 
gland is converted into a mass of fatty connective tissue. 

Congenital Abnormalities. — Complete absence or various minor 
irregularities of the thymus may occur; at times it is found enormously 
hypertrophied. In the latter case the root of the great vessels, the 
pericardium, and heart may be covered over and subjected to pressure by 



748 



A TEXT-BOOK OF PATHOLOGY 



the enlarged thymus, and sudden death (mors thymica) seems at times 
due to this cause. The purely mechanical explanation cannot, however, 
be accepted without question in all cases. There has been evidence in 
some instances that other causes were probably operative; but the whole 
question is still unsettled. Swelling of the thymus is a part of the 
so-called status lymphaticus, when it is associated with swelling of all lymph- 
oid tissues. It is noteworthy that the medulla of the thymus is hyper- 
plastic, while the cortex is unchanged. The cause of the condition and 
its fatal outcome is unknown. Thymic asthma, so-called, has been 
attributed to the mechanical effects of enlargement of the glands, a 
theory which receives considerable support from the curative effect of 
extirpation of part or all of the gland and of reduction of the hyperplasia 
by x-ray treatment. 

The physiology of the thymus gland is still obscure. That it has a 
relation to growth and development, especially bony growth, is probable 
but definite statements are scarcely warranted. 

Circulatory Disturbances. — Intense congestion and punctate hem- 
orrhages may be found in cases in which death has occurred from 
asphyxia. 

Inflammation as a primary disease is of doubtful occurrence, but 
abscesses may occur in cases of general pyemia, or from extension of 
suppurative affections of adjacent parts. 

Infectious Diseases. — Syphilis occurs in the form of gummata, 
especially in the newborn. Caseation and softening of the gumma 
may occur, and a resemblance to abscess is thus produced. Miliary 
or caseous tuberculosis occasionally invades the thymus gland. 

Tumors. — The thymus or its remnant is not infrequently the 
place of origin of lymphosarcoma of the anterior mediastinum. 
Tumors having this origin may be recognized by their shape and by 
the regularity of their outlines, the lymphosarcomata (lymphadeno- 
mata) of the lymphatic glands of the anterior mediastinum having a 
more irregular lobulated appearance. Ordinary round-celled sarcoma 
has been described, and epithelioma springing from the corpuscles of 
Hassall has been seen in a few cases. Dermoid cysts and angiomata 
have been seen. 

THE PITUITARY BODY, OR HYPOPHYSIS CEREBRI 

The hypophysis is a small glandular organ, situated at the base of 
the brain, lying upon the upper surface of the body of the sphenoid 
bone, and further protected posteriorly by a bony wall, forming a 
cavity which is known as the sella turcica. It varies slightly in size, the 
average weight in the adult being from 0.59 gm. (Schonemann) to 0.48 gm. 
(Comte). It reaches its maximum between twenty-one and forty years 
of age. 

The hypophysis is a double organ, developed from the central nervous system 
and from the alimentary canal. The nervous part originates from the middle pri- 
mary cerebral vesicle as an evagination from the cavity. This forms the infun- 
dibulum and the small posterior lobe. The larger anterior lobe, or true pituitary 
gland, appears to arise from two sources, one, the primitive oral tissue in early embry- 
onal life, and the other the anterior portion of the alimentary canal; both portions 



DISEASES OF THE DUCTLESS GLANDS 



749 



become contracted at their origins, fuse, and are ultimately separated from the 
alimentary canal, although this separation is not complete in some of the lower 
vertebrata. The similarity of origin of the pituitary and thyroid gland doubtless 
accounts for their probable related functions. Histologically, the organ may be 
divided into three parts: the anterior portion of the anterior lobe is composed of 
somewhat polygonal epithelium enclosed in alveoli, whose walls are made up of 
fibrous connective tissue. These groups of cells are very irregular, although some- 
times they are arranged about the periphery of the cavity, leaving in the center a 
small lumen, which, more frequently than not, is filled with an oxyphilic homogeneous 
mass that is supposed to be colloid. The amount of connective tissue is usually 
relatively small, and it contains a considerable proportion of cells as compared with 
connective tissues of other parts of the body, and is exceedingly vascular. The 
cells are of two kinds, the ehromophilic and the chromophobic. The former are 
further divided by Comte into the eosinophilic, in which the protoplasm stains deeply 
and homogeneously with eosin, and usually contains vacuoles; and the cyanophilic 
cells, in which the protoplasm colors dark blue with hematoxylin, and rarely contains 
vacuoles. The protoplasm of the chromophobic cells does not stain. Some authors 
consider that these distinctions are not morphologic, but only indicate that the 
different cells are in different stages of secretory activity. The posterior part (pars 
intermedia) of the anterior lobe usually contains, in man, a small bilobed cavity lined 
with cylindrical ciliated epithelium. In addition, there are also a few larger cavities 
lined by columnar or polygonal epithelium, and usually filled with colloid material. 
The posterior or nervous lobe consists of neuroglia tissue, and, according to Berkeley, 
a few ganglion-cells containing an excess of pigment, and some varicose fibers may be 
found in it. Kolliker, however, denies that there is any nervous tissue at all in the 
posterior lobe, and has been able to find nothing but neuroglia. It contains epi- 
thelial cells derived from the pars intermedia and a certain amount of colloid matter. 

If we can accept the assertions of those who have systematically 
examined large numbers of these bodies, a normal gland is the exception ; 
thus, Schonemann found only 27 normal specimens in 110 cases, and 
Comte 33 in 108. 

Hypertrophy of the hypophysis occurs in cretinism, myxedema, 
and acromegaly. In some of these cases the enlargement is due to 
tumor formation; in others, particularly in those occurring as a result 
of removal of the thyroid gland, it appears to be compensatory, or 
rather, as the functions of this gland and the thyroid cannot be exactly 
identical, at least vicarious. This enlargement, often apart from 
tumor formation, may be very considerable. De Conlon records a case 
in which the hypophysis weighed 1.55 gm., and, aside from an apparent 
proliferation of the epithelium cells, was normal in structure. 

Moderate hypertrophies or perhaps congestive swelling of the 
hypophysis seems at times to occur in women during menstruation or 
pregnancy. 

Circulatory Disturbances. — The gland is excessively vascular. It 
is possible that in some cases this vascularity may increase and give 
rise to a true hyperemia, although it is difficult to be certain of this. 
In case of passive congestion resulting from thrombosis of the cavernous 
sinuses edema may be present. Hemorrhage in the gland is a frequent 
agonal phenomenon. In these cases the blood-cells, normal in appear- 
ance, are found infiltrating the connective tissue stroma. Hemorrhages 
during life may occasionally occur, and give rise to small, deepty pigmented 
areas of softening, which ultimately form scars. 

Inflammation is usually secondary and suppurative. One of the 
authors has observed a case in which the anterior lobe was infected from 



750 



A TEXT-BOOK OF PATHOLOGY 



the parotid gland, probably as a result of ascending infection along the 
retropharyngeal lymphatics. In this case the capsule enclosing the gland 
was inflamed, and there were small collections of round cells in the sub- 
stance. 

Degenerations. — The most important and frequent is colloid degen- 
eration, the colloid material being found in' the cavities of the epithelial 
nests, or even as small masses in the connective-tissue septa. This 
may be looked upon as almost physiologic. It seems to be increased 
in those conditions in which we have reason to suspect increased func- 
tional activity of the glands, but also is more pronounced in cases 
of partial atrophy. Amyloid infiltration occurring in the blood-vessels 
has been observed in cases of general amyloid disease. The walls of 
the blood-vessels frequently undergo hyaline degeneration in old age. 

A sort of cheesy or liquef active necrosis is also observed in the 
center of adenomatous formations, and is probably due to pressure- 
necrosis, as a result of the limited space in which the hypophysis is 
placed. 

Infectious Diseases. — Of the infectious inflammations, the only 
ones of importance are tuberculosis, in the form of miliary tubercles, and 
syphilis, in the form of gummatous nodules. Occasionally a large 
single gumma has been observed. 

Tumors are the most interesting and important pathological con- 
ditions that occur, and there is still considerable difference of opinion 
regarding their nature. 

Cysts are very common, particularly a form of cystic degeneration 
with distention of the follicles by colloid substance. These are almost 
normal in old age, the only interesting feature being the atrophy and 
disappearance of the epithelial cells. Teratoid cysts have been described, 
but are much less frequent than would be expected from the com- 
plicated embryology of the gland. Of this nature is the myoneuroma 
described by White. 

Of the pathologically malignant tumors, the most important is the 
sarcoma. This is usually round-3ell or spindle-cell in type, and appar- 
ently springs from the capsule of the gland and replaces its substance, 
but rarely infiltrates the surrounding tissues or gives rise to metastasis. 
Cases have been reported as lymphosarcoma in which there were numer- 
ous collections of round cells in the alveoli of the connective tissue and 
some hypertrophy of the latter; apparently, however, no other lymphatic 
organs were involved. 

Glioma and endothelioma have been seen. 

Adenoma of the hypophysis causes increase in the size; the organ 
remains soft or may be slightly indurated, and is of normal color. The 
resistance of the bony structures that surround it may cause the gland 
to assume extraordinary shapes. Microscopically, there is proliferation 
of the epithelial cells, which form long tortuous and sometimes branched 
tubes, and often complete atrophy of the nervous lobe. These tumors 
have been described particularly in connection with the disease known 
as acromegaly. 

Pathological Physiology. — Removal of the posterior lobe of the 
pituitary body (Paulesco) seems to show that it is not essential to life. 



DISEASES OF THE DUCTLESS GLANDS 



751 



Removal of the anterior lobe is rapidly fatal, but partial ablation is 
followed by decreased growth, persistence of infantile characters, fat- 
ness, atrophy of the sexual glands, and enlargement of the thyroid. 
Feeding experiments and the use of extracts show that the posterior 
lobe elaborates a substance similar in action to epinephrin. It raises 
blood-pressure and stimulates smooth muscle-fibers (intestine, uterus) : 
is diuretic and galactagogue. It also affects carbohydrate metabolism, 
causing glycosuria when injected experimentally. 

The relation of the pituitary to acromegaly first opened the way to 
a recognition of the functions of the gland. In the majority of cases of 
acromegaly, adenoma of the pituitary occurs, and investigators agree 
that the cases where manifest disease of the pituitary is not found, func- 
tional hyperactivity is present. Disturbance of carbohydrate metabolism 
causing glycosuria is not unusual in acromegaly and may be related to 
hyperactivity of the pituitary or possibly to associated disturbance 
(pressure?) in the posterior lobe. Enlargments of the thyroid and 
changes in the sex-glands may be associated with pituitary disease. 

Several types of hypophyseal disease are recognized, and it is at 
present difficult to determine the seat and nature of the disturbance of 
function. 

Gigantism has been found associated with disease of the anterior 
lobe when this occurs in early life, as acromegaly develops when the 
disease occurs in later years. Both conditions are ascribed to increased 
function of the anterior lobe. 

Infantilism, fatness, and lack of sexual development (Frohlich's 
syndrome) are ascribed to decreased function of the anterior lobe. 

Polyuria (diabetes insipidus) occurs in connection with diseases of 
the pituitary and adjacent structures. 

THE PINEAL GLAND, OR EPIPHYSIS CEREBRI 

The pineal gland, or epiphysis cerebri, is an outgrowth from the roof 
of the posterior portion of the anterior vesicle of the brain. Its base 
is soon constricted, and it is finally completely separated from the pri- 
mary cerebral vesicle and enclosed in a sheath of connective tissue which 
is surrounded by pia mater. Histologically, it is found to consist of septa 
of connective tissue, dividing it into numerous alveoli, in which are 
found epithelial cells, some of which are branched. It is very vascular, 
and contains a plexus of sympathetic nerve-fibers. 

It has lately been asserted that this gland has something to do with 
nutrition in the young, assisting and regulating metabolism and growth. 
It is thought by some to regulate sexual development. 

At all ages it contains small calcareous concretions (acervulus, brain- 
sand), which must, therefore, be looked upon as physiological. It is 
sometimes enlarged in acromegaly and cretinism; this may be a result 
of simple hyperplasia of the epithelial structures, giving rise to adenoma- 
tous or strumous formations, or due to neoplasms. As a result of its posi- 
tion it may in these conditions occlude the aqueduct of Sylvius or the veins 
of Galen and produce hydrocephalus. Pathologically, aside from the 
calcareous infiltration already mentioned, hyaline degeneration of the blood- 
vessels may occur. There are usually signs of inflammation, more or less 



752 



A TEXT-BOOK OP PATHOLOGY 



marked, in cases of meningitis, which may even lead to pus formation. 
Of the tumors, the most important are probably sarcomata springing from 
the connective-tissue septa. Adenomata may also occur. Cystic condi- 
tions, associated with the presence of hair, cartilage, and other tissues, 
have been described. 

Tumors and other diseases of the epiphysis, aside from local effects, 
have been found to occasion premature growth and sexual development. 

THE CAROTID BODY 

The Carotid body is a ductless gland lying at the bifurcation of the com- 
mon carotid artery. It varies in length from 3 to 7 millimeters and is of 
a grayish pink color. Histologically it consists of a very rich network of 
capillaries, in places arranged somewhat like glomerules, in the inter- 
spaces of which he large vacuolated epithelioid cells, some round, others 
cylindrical. When fixed in chrome salts, a certain percentage of the cells 
takes a brownish coloration, thus alligning themselves with the chromaf- 
fin system, so well seen in the adrenal and ganglia; there may indeed be 
found definite ganglion cells within the capsule of the gland. It is be- 
lieved, judging from the staining reaction and certain experimental evi- 
dences, that the secretion has something to do with blood pressure; it is 
also thought that glucose metabolism is controlled in some way. The 
carotid body is especially noteworthy because tumors arise from it. They 
were originally placed among the endothelial growths but since the organ 
has lately been classified among the nervous tissues, they should be con- 
sidered as gangliomata. Such growths form red soft masses from which 
much blood can be squeezed. Microscopically they resemble the normal 
gland, including the alveolar arrangement and chromaffin cells. Meta- 
stasis is not common but may occur, to the liver especially. Growth 
is slow and the nature is usually benign. 



CHAPTER VII 



DISEASES OF THE URINARY ORGANS 
The Kidneys 
congenital anomalies 

Absence of one of the kidneys is frequently observed. Occasionally 
one kidney, instead of being completely absent, is atrophic or hypoplastic, 
while the opposite kidney may undergo compensatory hypertrophy. 
Both kidneys may be wanting in certain monstrosities. 

Congenital lobulation is quite common and is usually bilateral. 
The kidney is divided into separate lobes by furrows of variable depth. 
Occasionally there is almost complete separation into numerous lobules. 

A few instances have been observed in which there was a third kidney, 
and usually in these cases two of the kidneys lying to one side of the spinal 
column were agglutinated. 

Fusion of the two kidneys may occur, and there may result a single 
large organ, with a double pelvis and ureter lying to one or the other 
side, or a horseshoe-kidney may be formed. In the latter the two organs, 
which are generally displaced far downward, are united at their lower 
ends by a commissure passing across the spine just above the lumbo- 
sacral junction. The commissure may consist of normal kidney tissue 
or may be fibrous, more commonly the former. 

Congenital cysts and other congenital diseases will be referred to 
below. 

CHANGES OF POSITION 

Congenital Malposition. — Not rarely one of the kidneys is dis- 
placed downward. It may even occupy the pelvis. In other cases it is 
displaced laterally or forward, and has been found immediately beneath 
the anterior abdominal walls. 

Acquired malpositions may result from pressure upon the organ, 
or from elongation of the peritoneal reflections covering the kidney 
and absorption of the perirenal fat. The right kidney is more frequently 
displaced than the left, and the condition is especially common in women. 
Repeated pregnancies, the effects of tight lacing, and diseases or dis- 
placement of the liver are prominent causes. Movability or displacement 
of the kidney may be but a part of a general visceral descent (splanch- 
noptosis) ; according to Coffey it is frequently associated with a mobile 
cecum, or lack of proper adhesion of the whole mesocolon to the parietes. 

Several grades of movability or displacement may be distinguished. 
In the first, the perirenal fat is wanting, and the kidney is more movable 
beneath its peritoneal covering than is normal. This occurs in a large 
proportion of women, and usually affects the right kidney. In more 
48 753 



754 



A TEXT-BOOK OF PATHOLOGY 



advanced grades the peritoneal reflection covering the kidney is elon- 
gated and considerable movability of the organ within the abdomen 
results. The kidney may be moved from side to side, downward as far 
as the pelvis in some cases, or upward to the normal position or under 
the ribs. In a third group of cases the kidney, lying within an elongated 
peritoneal pouch, is retained in an abnormal position by adhesions. 

Results.— Twisting of the pedicle may lead to serious circulatory 
disturbances, or twisting of the ureter with retention of urine, sometimes 
causing hydronephrosis. Pressure of the displaced right kidney upon 
the duodenum may lead to dilatation of the stomach. 

CIRCULATORY DISTURBANCES 

Anemia of the kidney may occur as a part of general anemia. The 
kidney is light in color and rather hard in the earlier stages; but if the 
anemia persists, degenerative softening and enlargment may ensue. 

Complete arrest of the blood-supply, produced experimentally, 
leads to rapid necrosis of the kidney, the organ becoming ashen-gray 
in color and of a homogeneous structure, so that the separate parts (cor- 
tex, medulla, pyramids) are indistinguishable. Near the cortex, where 
some circulation is maintained by the capsular vessels, fatty degeneration 
is observed. Somewhat similar changes are met with in circumscribed 
areas in diseases in which the circulation in branches of the renal artery 
is obstructed. (See Embolism.) 

Active hyperemia of the kidney is generally a part of acute inflam- 
mation. It may result from irritant chemical poisons or from the toxic 
action of infectious poisons. The kidney is enlarged, dark red in color, 
and on section the cortical substance is found to be swollen and marked 
by dark red points — the Malpighian bodies. Sometimes punctate or 
linear hemorrhages may be observed. The urine is somewhat albumin- 
ous and hyaline casts occur. It is difficult to draw a sharp line between 
this condition and acute nephritis. 

Passive hyperemia occurs in cardiac and pulmonary diseases which 
impeded the circulation, or rarely as a consequence of thrombosis of the 
inferior vena cava or renal veins, or of other local causes obstructing 
the circulation in the renal veins. The kidney is enlarged and, on section, 
the cortex is found to be swollen, the substance of the kidney dark red 
in color, particularly in the pyramids in the vicinity of the large veins. 
The Malpighian bodies may be distinctly enlarged and dark red. 

Long-standing passive congestion leads to reactive hyperplasia of 
the interstitial connective tissue of the organ, and thus to a form of sec- 
ondary diffuse nephritis. In these cases the kidney becomes contracted, 
the surface somewhat irregular, and the capsule ofttimes adherent. 
The organ may be intensely hard and pigmented, and the term cyanotic 
induration is appropriate. 

The microscopical findings include enlargement of the tufts, with loss 
of the epithelium and distention of the capsule with albuminous transu- 
date, and hyaline or connective-tissue thickening of Bowman's capsule. 
There are various degenerations of the parenchyma, in response to which 
some of the epithelium shows multiplied nuclei or enlargement of the 
cell to appear like syncytial cells. There may be edema, small hemor- 



DISEASES OF THE UKINARY ORGANS 



755 



rhages, and almost always an excess of deposited blood-pigment. Hya- 
line casts are always found. The connective tissue is irregularly increased 
over the organ. 

The urine in passive hyperemia is, as a rule, deficient in quantity, 
and contains variable quantities of albumin and hyaline or granular 
tube casts. 

Hemorrhage. — Punctate hemorrhages may occur in cases of intense 
active or passive hyperemia, the extravasation of blood occurring in the 
interstitial tissues, in the uriniferous tubules, or within the capsule of 
Bowman. Similar hemorrhages may be observed in acute or chronic 
nephritis. In these cases the extravasation of blood may occur by dia- 
pedesis of by actual rupture of the capillaries. Small hemorrhages may 
occur in the perirenal tissues in certain 
of the hemorrhagic diseases. Large hemor- 
rhages occur within the kidney substance 
only in cases of traumatism. Extravasa- 
tions of blood between the parenchyma 
and capsule occur from trauma, infarction 
and rarely without discoverable cause; the 
condition thus formed is called a perirenal 
hematoma. 

In so-called 11 essential hematuria" the 
cause is obscure and the lesions variable; 
at times there is no anatomical change 
discoverable while in some cases passive 
congestion from vascular kinks, varicosities 
or ulcerations in the pelvis, or small 
parenchymatous hemorrhages are found. 

Edema of the kidney results from ob- 
struction of its venous circulation. The 
kidney becomes enlarged and soft, and the 

Spaces between the Convoluted tubules Fig. 357. — Anemic infarcts of 

(the primary lymphatic spaces) are dis- the kidney surrounded by a zone 

. . ., i i mi • * j i of hemorrhagic infiltration (Kauf- 

tmctly enlarged. I here is associated ma nn). 
congestion in these cases. Simple edema 

of the kidney may result from obstruction of the urinary outflow. 

Thrombosis of the renal veins or their branches is rare. It 
causes intense hyperemia, hemorrhages, and edema, and later necrosis 
and degenerations. 

Embolism is very common in the branches of the renal arteries, 
especially in cases of disease of the aortic valves or atheroma of the aorta 
with fibrinous deposits upon the atheromatous areas. The blood-vessels 
of the kidney correspond closely to the conception of terminal arteries, 
and infarction is, therefore, the usual result. In most cases the infarcts 
are light-colored areas (anemic infarcts) having a wedge shape, the base 
of the wedge being directed toward the capsule of the organ. A zone of 
reactive hyperemia or hemorrhage usually separates the infarct from the 
surrounding structures (Fig. 357). Less frequently there are purely 
hemorrhagic infarcts, the entire area being dark red in color. Minute 




756 



A TEXT-BOOK OF PATHOLOGY 



emboli may lead merely to punctate hemorrhages within the kidney, or 
to ecchymotic extravasations on the surface. 

The white or anemic infarcts undergo gradual necrosis and absorp- 
tion, with cicatrization or encapsulation, the contents in the latter case 
remaining as a dry detritus. The hemorrhagic infarcts more commonly 
soften, and finally terminate in cicatrization or in the formation of small 
cysts. In cases of infective embolism the anemic or hemorrhagic infarct 
may rapidly break down and form a metastatic abscess. 

INFLAMMATIONS 

Inflammation of the kidneys may affect the substance (nephritis), 
the mucous membrane of the pelvis (pyelitis), or the capsule and periph- 
eral portions (perinephritis) . 

NEPHRITIS 

Nephritis is the term given to a number of forms of degeneration 
and inflammation of the substance of the kidney. The term " Bright 's 
disease" is a clinical rather than pathological one, being applied to various 
kinds of kidney disease attended with albuminuria and dropsy. As a rule, 
however, the name Bright's disease and nephritis are used synonymously. 

Etiology. — Nephritis is due in the majority of cases to irritants which 
reach the kidney through the circulation. Intense acute nephritis may 
result from various poisons, particularly such as attack the parenchyma 
of organs, and are, therefore, known as parenchyma posions. Among 
these, arsenic, mercury, phosphorus, cantharides, and turpentine are 
conspicuous. A second group of cases, and perhaps the largest of 
all, owe their origin to infections of various kinds. Nephritis is a com- 
mon complication or sequel of scarlet fever, cholera, septicemia, diph- 
theria, and many other infectious diseases. In these cases the micro- 
organisms themselves may reach the kidney through the circulation 
as in typhoid fever, anthrax, or pneumonia, or the renal irritation may 
be caused by the toxins, as in cholera and diphtheria. Nephritis is 
common in streptococcus infections, but whether by circulating toxins 
or by the cocci themselves is not always determinable; the latter is 
probably more important since kidney lesions are not often uniformly 
distributed as would be expected were a circulating toxin solely responsi- 
ble. It seems likely that clumps of bacteria are caught as emboli by the 
glomerular capillaries whereupon thromboses and hyaline necroses are 
produced; bacteria have been found in such areas in septicemic cases. 
This mode of origin seems widely accepted as the usual one for glom- 
erulo-nephritis and therefore for secondary scleroses. Certain chronic 
infections lead to nephritis by the action of the toxins or by slow nutritive 
disturbances. Such is the case in syphilis, tuberculosis, and malaria. 
Auto-intoxication occasions certain cases, as in the nephritis of gout 
and diabetes. 

In the minor infections, whether focal or generalized, low grades of 
degeneration or inflammation may be found in the kidney. These may 
be diffuse or insular, and may lead to chronic Bright's disease if the 
insults be repeated. Thus, in subinfection there may be a continued 
assault of very low power, but great in the aggregate. In focal infec- 



DISEASES OF THE URINARY ORGANS 



757 



tion, for example from the tonsil, bacteria or their toxins may be carried 
by the blood to the kidney. Our newer conceptions of these subdued 
forms of infection may thus explain some of the cases of nephritis 
heretofore called idiopathic or cryptogenic, the latter term being in a 
sense correct, as we seldom know the source and the infecting germ. 

In a small proportion of the cases, nephritis results from irritants 
reaching the kidney through other channels than the circulation, as in 
pyelonephritis, a condition consequent upon inflammatory processes 
ascending from the bladder and ureters, or as in nephritis secondary to 
extrarenal disease (psoas abscess). 

Low-grade renal inflammation may result from chronic congestion 
of the kidneys in consequence of cardiac and pulmonary disease. On 
the other hand local arterial degenerations in the small vessels of the 
kidney may lead to diffuse overgrowth of connective tissue which may 
not involve the secreting structures at all or at least not at first, benign 
sclerosis, but later the interference with circulation may be great enough 
to incapacitate the glomeruli and a true arteriosclerotic nephritis appears. 

The pathological classification of diseases of the kidney has never 
been quite satisfactory, nor is it so today, chiefly because of our imperfect 
knowledge of the functions allotted to the various finer renal structures. 
Recent advances in physiological and clinical research have supplied 
certain data upon which a newer classification has been based, one which 
offers fairly definite criteria for anatomical classification and clinical 
interpretation and prognosis. Before presenting the pathological divi- 
sions it might be well for a short space to review the anatomy and physi- 
ology, both normal and pathological, of the organ. 

The kidney is a compound epithelial gland within which blood vessels 
are so intimately associated with the secreting structures and in so defi- 
nite a fashion as to be a part of the peculiar micro-anatomy of the organ. 
The particulate units are first tubules, straight, convoluted, or swollen 
out into a cavity which contains the other elements, tufts of intricately 
wound capillaries, the glomerulus. It is perhaps well to emphasize that 
the tubule begins as the capsular space of Bowman; thence it passes with 
an isthmus, into the proximal convoluted tubule which ends by turning 
toward the medulla, there making Henle's loop as it returns to the cortex 
in the so called medullary ray. Once again in the outer layer, another 
convoluted part, the distal, is formed, after which, by the junction of 
many such systems, a discharging tubule arises; this leads to the pelvis. 
The capsular space and the capillary tuft within it are covered with flat 
epithelial cells. The convoluted parts of the tube are lined with large 
cuboidal cells having indefinite mural outlines and rather large nuclei 
supplied with loosely arranged chromatin. Marked striation of the 
protoplasmic granulations is characteristic of these epithelial cells, and 
in the proximal sections it seems continued on the free edges of the 
cells in a fashion resembling cilia. The discharging pathways are small 
canals, their epithelia being clear, well separated and the nuclei deeply 
stainable. The blood supply derived from the renal arteries, runs up 
the medulla in septa corresponding . to the fetal lobulations and, after 
giving off the vasa recta sends off lateral branches which pass directly to 
the glomeruli. The efferent artery from the tuft divides into many 



758 



A TEXT-BOOK OF PATHOLOGY 



capillaries which form a plexus about the tubules; these latter combine 
to form the veins. 

The cortex of the human kidney, normally measuring 4 to 6 milli- 
meters, contains the glomeruli, the major part of both proximal and dis- 
tal convoluted tubules and the beginning of the discharging canals. The 
medulla is usually from 1.5 to 2 centimeters wide, and contains the re- 
mainder of the tubule. 

The function of the kidney is to excrete urine, normally a solution in 
water of waste crystalloids. The exact manner in which this function is 
executed is not known but whereas it was formerly believed that simple 
filtration or osmosis would be adequate explanation, it is now thought that 
some secretary or absorptive power resides in the tubular cells. The blood 
as it passes through the glomerular capillaries pours into the space of 
Bowman a dilute plasma, therefore being, as it leaves the tuft to circu- 
late in the peritubular plexus, decidedly concentrated and requiring the 
return to it of sufficient water to maintain its proper concentration. 
Moreover as all kinds of salts would be filtered through the tuft, both 
necessary and excrementitious, the required or useful ones would have to 
be reabsorbed ; such reabsorption is thought to occur in the tubules. The 
epithelium of all divisions is normally impassable for colloids in the blood. 
Important factors influencing the amount of crude urine filtered through 
the glomerules are the blood pressure in the capillaries and the pressure 
within the tubules; the greater the blood pressure the more the filtration, 
the higher the intratubular pressure the less the filtration. To this is 
added the forces of osmotic diffusion through the basement membrane and 
cells. Abnormal constituents will appear when the glomerular epithelium 
permits the passage of blood colloids or when the tubular lining, because 
degenerated, does not permit the return to the blood of necessary salts. 
It is probably not true that the tuft excretes the water and the tubules 
the solid matter as formerly thought. Moreover abnormal substances 
like sugar will appear when their osmotic partial pressure in the blood is 
greater than normal so that resorption from the crude urine cannot occur. 
The appearance of normal substances in unusual amounts depends prob- 
ably more upon tubular, that is resorptive, damage than upon ab- 
normalities in filtration. The excretion of certain test dyes notably 
phenolsulphonephthalein depends upon the condition of both elements 
but perhaps more upon that of the tufts, while the fixation of specific 
gravity seems to depend upon a relation between the ability to filter and 
the ability to reabsorb. Dye tests are best considered as indications of 
total kidney function and not as of any particular unit. Albuminuria 
may be due to damage of the glomeruli which allows blood plasma to 
filter through, or to inflammatory or degenerative change in the epi- 
thelium freeing both cellular and blood protein. 

Normally about 1500 cc. of urine are excreted daily and of this less 
than 50 per cent, should be passed during the night hours. The specific 
gravity, normally between 1016 and 1018, tends to become lower with 
increase of ingested fluid and heightened arterial pressure, while conges- 
tions and degenerations, interfering with the resorptive mechanism in- 
crease the concentrations of solids and therefore the specific gravity. 
Insofar as the individual chemical components of the urine are concerned, 



DISEASES OF THE URINARY ORGANS 



759 



nitrogen is the most important, while others include aromatic oxyacids, 
chlorides and sulphates. Nitrogen is found in urea, ammonia, creatinine, 
creatin, purin bodies and in traces of amino acids. This element is normally 
excreted in non-protein form, being derived from nonprotein nitrogen 
of the blood where it exists in concentration of about 25 mg. per 100 cc. 
Urea nitrogen represents from 60-90 per cent, of the total nitrogen excreted 
and was therefore formerly thought to indicate the degree of excretion 
of waste nitrogen. It has been found, however, that the urine urea may 
remain within normal limits and the blood urea be at a pathologically 
high level. Defective urea nitrogen elimination is especially associated 
with acute and chronic glomerular lesions and less definitely with prim- 
ary tubular degeneration although in all late cases with diminished 
general renal function, decreased excretion and increased blood nitrogen 
occurs. The normal total daily nitrogen elimination is 10-15 grams. 
Ammonia is present in the urine to the extent of 0.7 g. per day, its 
quantity varying indirectly with the ability of the tissues to transfer 
ammonium into urea. Creatinine is excreted at the rate of 10 mg. per 
kilogram of body weight; the blood contains 1-2 mg. per 100 cc. It is 
readily filtered out of the blood and when the amount excreted is low and 
the blood content is high, severe damage of the renal function exists. 
Uric acid is present in the blood normally in amounts of 1.6 mg. per 
100 cc. and in the urine to the extent of .5-1 gram per day. Its retention 
is often due to other than renal disease; if and its salts are not very 
soluble and its quantity varies definitely with the diet; for these reasons 
its relation to lesions of the kidney is not clear but in late nephritis there 
is apt to be an increase in the blood. 

The oxyacids, phenol, skatoxyl, indoxyl and the like, are formed by 
decomposition from aminoacids in the intestines. Indican is an oxida- 
tion product and is a rough indicator of intestinal putrefaction but not 
of renal function. 

The chlorides are excreted as such through the kidneys but their 
amount varies very much with the diet, the circulation and the condition 
of the bowels. Their threshold in the circulating blood seems about 
5.62 grams per litre and they are excreted at the rate of 8-20 grams per 
day. Accumulation usually accompanies dropsy or general retention of 
water in the body but with tubular nephritis a definite increase in the 
blood is also noted. Since however, glomerular lesions are at times asso- 
ciated with chloride retention, and because there seem to be many factors 
affecting the blood constant of this salt, no conclusions can be drawn as to 
the relation of the kind of lesion and chloride metabolism. Its excretion 
is disturbed very early in all nephritides and retention exists in all 
advanced types. 

Although pathological physiology varies in the different anatomical 
forms of nephritis and it is our intention to treat of it for each of the types, 
still there are several pathological states and clinical evidences which 
deserve separate discussions. The blood pressure shows a definite re- 
lationship to certain forms of tissue change notably in the glomeruli. 
Indeed it can be stated that only forms of nephritis that have vascular 
and glomerular alterations show heightened blood pressure. It would 
seem that the tufts hold back substances which increase tension. There 



760 



A TEXT-BOOK OF PATHOLOGY 



is no proof that it is due to retained water making greater bulk within 
blood vessels. This may or may not be associated with arteriosclerosis; 
in the acute cases it is usually not connected with vascular fibrosis but 
it is always present in the true arteriosclerotic kidney. The increased 
pressure may have the effect of causing the heart to enlarge, especially 
the left side; such an occurrence is the rule in late chronic generalized 
nephritis. Degenerations of the myocardium are common and dilatation 
may occur. This cardiac degeneration, that in the vascular walls, the 
congestion or even inflammation of serous and mucous membranes have 
all been laid to the retention of materials in the blood which should have 
been excreted but what these are is still unknown as we shall see in " ur- 
emia." It maybe, in the case of the mucous surfaces, that an attempt 
is being made to excrete such substances but it is also probable when the 
changes are inflammatory that bacterial growth is encouraged by conges- 
tions or irritations, resulting from the nephritis. On the whole however, 
the effect of mild and moderate grades of kidney disease upon the general 
metabolism is surprisingly slight. In the severe acute forms and in the 
late advanced generalized cases of nephritis there is an intoxication of an 
acidotic nature which varies in its manifestations according to the type 
of lesion. Some of the acids are probably derived from defective gastro- 
intestinal function whereby putrefaction arises; this is indicated by the 
increase of oxyacid acids and combined sulphates in the urine. Other 
cases present that complex of symptoms known as uremia but whose cause 
is still obscure. There is a decided acidosis in uremia as indicated by 
lowered C0 2 tension in the alveolar air and an increased hydrogen ion 
concentration in the blood. A toxic oily substance, urinod, has been 
found in the urine, alleged to be active in uremia, and a crystalloid of 
similar poisonous properties is reported. There is no proof today that 
uremia is due to the degradation products of renal epithelium, to urea, 
creatinin or other accumulations or indeed that it is due to any one sub- 
stance, for injection of the various excretives has not produced the condi- 
tion in lower animals. Edema in nephritis is usually an expression of the 
inability of the glomerular apparatus to excrete water and salt, retention 
of both being closely associated with accumulations in the tissues and 
cavities; it is more common in the tubular lesions. 

The determination of a renal lesion today is based upon the efficiency 
of the kidney to excrete and the evidence for such a judgment rests 
upon the presence of albumin in the urine, the excretion of phenolsulphone- 
phthalein, the maintainance of the normal specific gravity, the presence of 
casts and the blood content of nonprotein nitrogen and chlorides. 
Some of these factors have been discussed elsewhere but others deserve 
note at this point. When a test dose of phenolsulphonephthalein is 
injected, the normal kidney will excrete 60-30 per cent, of it in two hours; 
any reduction of this means some form of renal inefficiency. The total quan- 
tity of urine is subject to great variations that are in a measure peculiar for 
different forms of nephritis; for example it is reduced in acute forms and 
increased in the intermediate and chronic forms. The appearance of 
the urine is seldom characteristic except perhaps for the presence of 
blood in severe acute lesions or the heavy deep amber color in acute 
tubular forms. Albumin appears chiefly as serum albumin although 



DISEASES OF THE URINARY ORGANS 



761 



globulin usually accompanies it; the latter is more abundant in hemor- 
rhagic cases and where amyloid has been deposited. 

Casts are found in the urine in all cases of degenerative and inflam- 
matory nephritis, and masses of indefinite hyaline substance, bits of 
coagulum or even fatty matter occur within the tubules and in the space 
of Bowman. In the former place they may remain as granules or balls 
or may agglomerate into cylindrical forms — casts of the tubular lumen — 
which can slip down into the pelvis and appear in the urine. The ma- 
terial of which they are composed comes from degenerated epithelia or 
from exudation of serum. At times the tubular lining may desquamate 
thus forming cellular casts but this is unusual; more often a few epi- 
thelia adhere to hyaline casts. Other cellular casts may be made up of 
leucocytes or red blood cells, being chiefly found in purulent and hemor- 
rhagic nephritis respectively. Hyaline casts, the commonest variety, are 
translucent lightly colored straight, or spiral bodies .01 to .03 mm. in 
diameter, and greatly varying in length. Waxy casts, a form of these, 
are wide, apparently rigid, moulded and glistening, whence the name. 

Cylindroids resemble hyaline casts but are narrow, tape or thread- 
like, twisted bodies having a drawn out tapering end or tail. They do 
not indicate a definite renal lesion, though often associated with hyaline 
casts, but are also derived from other parts of the urinary tract. Granular 
casts are made up of fine or course granules sometimes upon the basis of 
a hyaline cast, at others being wholly granular. They are light or dark 
brown or glistening, an appearance thought to be due to fat droplets. 
The cells of the urine are of little significance in nephritis aside from 
leucocytes and red blood cells. One may at times recognize renal epi- 
thelium or the compound granule cells, probably of both epithelial and 
leucocytic origin, in chronic cases. 

Pathology of Nephritis. — A review of the anatomy and physiology 
of the kidney makes it at once apparent that a classification of lesions 
upon a structural basis is exceedingly difficult. The older systems of 
Weigert and Ziegler have not been found to fit with modern clinical 
observations — factors which must be reckoned with to produce a satis- 
factory classification. The one we give here is in use at the University 
Hospital and represents a combination of studies by Stengel and his co- 
workers with the work of Vollhard and Fahr, of Ophiils and of Christian 
and his associates. The basis of the subdivision is that tubular changes 
are usually characterized by marked albuminuria and casts, edema, high 
urinary specific gravity, oliguria, moderate or low blood pressure and 
infrequent uremia, whereas when glomerular lesions predominate, there 
are high blood pressure, fixation of the specific gravity at a low point, 
long continuing toxic or uremic symptoms and a tendency to chronic 
change. It is at once seen that the modern system seeks to base an 
anatomical lesion upon clinical grounds, a method which it is hoped will 
be a safe one for the future. It should be emphasized, however, that, 
because of the close interrelationship of the various units in the kidney, 
there is no such thing as a pure nephritis. Tubular degenerations may 
be continued or followed by interstitial change and it is the rule for that 
form called glomerular to involve the general supporting tissue and the 



762 



A TEXT-BOOK OF PATHOLOGY 



epithelium, especially when progressive, since a healthy tubule cannot 
remain when its origin, the glomerulus, is damaged. 

The forms called tubular are for the most part degenerative and not 
actively infiltrative, but actively inflammatory types are also seen. 
There are also chronic lesions which begin as pure interstitial inflamma- 
tions or fibroses, only secondarily damaging the secreting elements — be- 
nign and arterial scleroses. The following system, although a fairly 
good working basis for pathologist and clinician, is not strictly an etiolog- 
ical one for similar lesions may arise from different causes. We know 
too little of the exact etiology to connect it with lesions, except perhaps 
in streptococcal glomerulonephritis and the arteriosclerotic kidney. 

Degenerative Tubular Nephritis (also called catarrhal nephritis, 
nephrosis, nephropathy). This form appears in a moderate degree in 
nearly all septicemias, like pneumonia and typhoid fever, but then 
seldom leads to serious consequences. The severe grades are seen in the 
so-called " kidney of pregnancy", in poisonings by corrosive sublimate, 
tartrates and chromates and at times in severe intoxications during in- 
fectious disease, notably cholera, diphtheria and yellow fever. The mild 
forms tend to recover by regeneration of the epithelium while many of 
the severe cases are followed by a chronic stage when there is also in- 
volvement of the glomerulus and connective tissue hyperplasia; this is 
one form of "large white kidney." 

Grossly such an affected kidney is swollen and rather opaquely pale 
but at times streaks of congestion are seen. The cortex is the affected 
area and may be poorly outlined from the medulla. .At a later stage, when 
there is some extension to the glomeruli and attempt at repair, the organ 
is mottled yellowish red, while if interstitial involvement is marked, it is 
pale brown, possibly irregular in outline, and firm. Microscopically the 
early and mild stages show merely cloudy or hydropic change in the 
epithelium of the tubules but more serious grades exhibit fatty disin- 
tegration and desquamation. To this may be added congestion in the 
tufts, which may go on to atrophy; hyperplasia of the capsular epithelium 
is also seen. Still later stages show distinct connective tissue overgrowth 
between the tubules, a condition that is usually not evenly distributed 
over the organ but more pronounced in some places than others. This 
last picture is one of the types formerly discussed as chronic parenchyma- 
tous nephritis. Some glomeruli remain in a good state of repair while 
others become obliterated. The tubular linings are low and the lumen 
wide. 

In the form following mercurial poisoning it is the rule to find calci- 
fication along the degenerated tubules. Prolonged suppuration may give 
rise to a tubular nephritis in which amyloid is laid down in the tufts, 
vasa recta and interstitial tissue ; this kidney may go on to contraction 
and is of a pale color. The degenerative nephritis of syphilis seems to be 
characterized by fatty degeneration because one almost constantly finds 
in the urine of such cases, doubly refractile masses of cholesterin esters in 
great abundance; these bodies may occur in small numbers in any severe 
degenerative nephritis. 

Physiologically tubular nephritis is characterized by scanty, often 
highly colored and heavy urine containing a considerable amount of 



DISEASES OF THE URINARY ORGANS 



763 



albumin and many casts; suppression of urine may occur in severe cases. 
There is marked depression and a moderate anemia. Edema is quite 
common, beginning early and moderately but often developing rapidly. 
Uremia is an infrequent occurrence. Blood pressure is not elevated in 
early cases. Nitrogenous excretion is not markedly altered but there 
tends to be a slight increase of nonprotein nitrogen and chloride in the 
blood. 



■ 



^1 * 



m 



^ _ 



Fig. 358. — The glomerulus of degenerative nephritis — some engorgement of capillaries 
and swelling of the glomerular epithelium but no exudation or infiltration-tubules on the 
other hand show cloudy swelling and granular disintegration and occasionally nuclear 
degeneration in the epithelium (Modified from Oertel). 



Glomerulonephritis. — This is the type of renal disease showing, most 
frankly and definitely, inflammatory processes. Toxins may possibly 
produce it but bacteria are probably much more common and potent; it 
is the kind explained above as beginning from bacterial emboli; scarlet 
fever and the streptococcus stand out preeminently in its causation. 
This form of affection can be limited or focal, or widespread over much 
of the kidney. The latter is to be considered first. Since it is an in- 
flammatory lesion, the tubular epithelium and interstitial tissue are not 
long in following the glomeruli in the process so that there is really a 
diffuse nephritis in the sense that all tissues are involved but not neces- 
sarily in the same manner or degree. This form of nephritis tends very 
definitely to become chronic or at least to leave a residuum of damage 
to the secreting structures, although its manifestations may be subdued 
for long periods. For these reasons, an acute, intermediate and chronic 
or late stage may be differentiated. 1 



764 



A TEXT-BOOK OF PATHOLOGY 



At first the organ appears slightly enlarged, with a rather pale widened 
cortex upon which the glomeruli stand out as congested points or, when 
there is infiltration into the capsule and tufts, as pale areas. An inter- 
tubular sprinkling of petechias or linear hemorrhages may be seen. At 
a later stage, if hemorrhages have been prominent within the organ, 
blotches of brown and red appear which may become quite darkly pig- 




Fig. 359. — Chronic diffuse nephritis with large and small retention cysts. 

mented at a still later time . When tubular degeneration has been marked 
the organ may be larger and pale with poorly outlined cortical markings. 
With the appearance of sufficient connective tissue to distort the tubules, 
irregular striae of pale gray and redder bands, the latter corresponding to 
intact or regenerated tubules, traverse the outer half of the organ, which 
is often reduced in size — the secondarily contracted kidney and one of the 



DISEASES OF THE URINARY ORGANS 



765 




Fig. 360. — Chronic diffuse nephritis, showing small cystic dilatations of tubules. 




Fig. 361. — Glomerulonephritis. Cellular increase in the tuft proper; a compound 
cellular crescent, the inner part being composed of proliferated and desquamated epithelia 
from the tuft and capsule, the outer part consisting of red blood cells, therefore hemor- 
rhagic. A moderate increase of nuclei seen outside the capsule (Modified from Aschoff). 



766 



A TEXT-BOOK OF PATHOLOGY 



forms previously called chronic interstitial nephritis. The organ is 
usually small, firm, mottled pale and red, with an adherent capsule. 

Histologically the initial lesions in such a kidney are thrombosis and 
swelling of the tufts, to which is usually added the appearance of large 
numbers of mononuclear cells within, and around t he capillaries and in the 
free space; the lining epithelium may degenerate or desquamate. These 
cells may cover and obscure the tuft or may collect in a cresentic shape 
between it and the capsule. This is known as the epithelial cresent but 
may be constructed of or include wandering mononuclears or even poly- 
nuclears. In some capsular spaces a hyaline or spongy coagulum may 
form, apparently by transudation; this too may form a cresent over the 
tuft. In hemorrhagic cases the space is filled with red blood cells. By 
reason of swelling of the capillary mass, it touches the capsule at some 
points, to which the inflammation may cause it to adhere. By this time 
active inflammatory changes together with thrombosis, have usually 
sealed the fate of the glomerulus and it is destroyed, replacement being 
made by connective tissue. 

During the first discussed glomerular charges the tubules belonging 
to it are usually swollen with cloudy and hydropic degeneration, their 
lumen containing amorphous albuminous bodies, red and white cells and 
casts. The supporting structure is nearly always the seat of slight round 
cell infiltration and fibroblastic increase which distort tubules and com- 
press vessels. There seems at times to be an attempt on the part of 
some glomeruli to hypertrophy in a compensatory manner. The vessels 
are apt to show walls slightly thickened by endoangitis but there is 
nothing peculiar about the amount or distribution of this change. The 
last stage, which may be designated as chronic diffuse or glomerulo-tubular 
nephritis, is a generally distributed process with hyaline fibrosis of most 
of the glomeruli, disappearance of many tubules and distortion of others 
by interstitial connective tissue. This form in the acute stage and the 
tubular form correspond to the older conception of parenchymatous 
nephritis. 

The functional pathology of glomerulonephritis is divisible into stages 
corresponding to its early activity, to a quiescent period that frequently 
occurs and to the termination. Sometimes the lesion develops rapidly 
and assumes a hemorrhagic character or at least a severe grade of glomeru- 
lar and tubular change, while in many instances an insidious beginning 
must be assumed because there may be no history of an acute attack. 
Perhaps this latter is the commonest for a true.interstitial nephritis of long 
duration, small crops of glomeruli being attacked by repeated embolisms 
or intoxications. In the acute stages there are scanty, heavy, dark 
colored urine of high specific gravity, abundant albumen and casts, blood- 
cells, and increase in arterial tension and a tendency to uremia; edema is 
not prominent. In the interval between the acute and terminal stages or 
during the insidious development, there may be no pronounced altera- 
tions in physiology although close observation over periods of time 
usually reveals a blood pressure with fluctuations but tending to be high, 
a mild grade of anemia and perhaps general depression. The blood 
during this period may or may not show an increase of nitrogenous 
bodies and chlorides. There is apparently enough obstruction to the 



DISEASES OF THE URINARY ORGANS 



767 



circulation and stimulation of the cardiac muscle to bring about a de- 
cided tendency to enlargement of the left heart. Urinalysis commonly 
reveals traces of albumen and a few casts. At any time during this stage 
an exacerbation of acute character may arise or complications like 
cardiac dilatation may appear. The establishment of the terminal 
stage of diffuse nephritis of glomerular origin produces a definite grade of 
anemia, a pasty yellow color of the skin, digestive disturbances and de- 
cided asthenia. The blood pressure is constantly elevated averaging 
for example 225 systolic and 140 diastolic; cardiac hypertrophy is the rule. 
Polyuria is observed and represents the effort to eliminate the normal 
quantity of solids by a kidney that is unable to concentrate; non-protein 
nitrogen and sometimes chlorides are at a high point in the blood. The 
specific gravity is usually fixed at 1010-13. Traces of albumin and 
hyaline casts are found. Albuminuric retinitis is a frequent complication. 
Uremia is the usual ending of such cases, a result greatly favored when 
cardiac decompensation adds the element of passive congestion of the 
kidney. Death from cardiac decompensation or cerebral hemorrhage 
may however occur before pronounced uremia has developed. 

The foregoing form represents widespread lesions involving most of 
the kidney structure and the effect of the action of considerable amounts 
of poison, but there are isolated, focal or limited lesions affecting the 
glomeruli, doubtless also the tubules, which arise during acute infections 
like scarlatina, pneumonia and the like, leaving irregular separate patches 
of interstitial change; to these the names focal, embolic, local productive 
nephritis have been applied. Perhaps this occurs as a repeated or con- 
tinuous affair in the insidious cases but, judging from the irregular outlines 
of certain kidneys long after infections, it may cease and heal at times. 
It might be emphasized again that there is no pure or single type of 
lesion nor a uniform progression in any one case and that one must 
look at the principal anatomic alteration, combined with its results, for 
a classification. 

The following are anatomical and pathological forms of nephritis that 
present no constant etiology or clinical evidences. 

Focal Glomerulonephritis arises as a result of the same causes as 
the general form but is limited to a small number of glomeruli. Endocar- 
ditis, acute and subacute, is perhaps the most prominent cause. It is 
commonly hemorrhagic in type, there being in the tuft crescentic accumu- 
lations of red blood cells and mononuclears; some cases however, as in 
scarlatina, show only tufts swollen to the limits of the capsule and entirely 
hidden by enormous collections of nuclei. At times the name septic 
might well be applied when polynuclear leukocytes dominate the field 
and small abscesses appear. In cases of focal glomerulonephritis the 
organ may be little changed or it may be swollen, firm and pale where there 
is accompanying cloudy swelling. The section surface is apt to show 
congested glomeruli surrounded by pale areas representing degeneration 
of the proximal convoluted tubules. When infective emboli are at the 
bottom of the matter, tiny pale areas, indicating abscesses, appear. 
The outcome of such a type of disease may be healing and scar tissue or, 
if not severe, the organ may completely recover. It is possible that a 
continuing therefore chronic, inflammation may remain but this is not 



768 



A TEXT-BOOK OF PATHOLOGY 




Fig. 363. — Acute nonsuppurative interstitial nephritis. There is in addition some tubular 
degeneration and desquamation. 



DISEASES OF THE URINARY ORGANS 



769 



clearly proven. During the acute stages there may be a slight reduction 
in the output of urine, moderate or considerable albumin and casts but 
there is no effect upon nitrogen excretion. Hematuria is often observed. 
The blood chemistry seems not to be affected and the renal function 
remains good. In late stages, pain has been reported. 

Having discussed those types of nephritis which seem to begin pri- 
marily in the tubules and tufts, the forms starting in the interstitial 
tissue must now be considered. The first to be discussed is probably 
always primarily in the connective tissue. 

Acute Interstitial Nonsuppurative Nephritis arises at times in diph- 
theria and scarlatina bat perhaps most often when these are combined 
with some other infection. The organ is slightly swollen and pale on the 
surface but may appear quite normal externally. On section it is usual to 
find irregular pale areas within the normal cortex and medulla, a picture 
due to the infiltration of mononuclear cells between the tubules and, to 
slight degree, to cloudy swelling of epithelium; the glomeruli are little 
affected to the naked eye or microscopically. The cellular infiltrate, 
usually lymphocytes but also including large mononuclears, spreads 
between the tubules in the affected areas, and indeed may be found within 
them. After the lesion quiets down fibroblasts and connective tissue may 
appear at this point. Clinical evidences of this lesion are uncertain. 
Urinary findings are not characteristic and we know nothing of the blood 
chemistry. 

Acute interstitial suppurative nephritis may be embolic or 
ascending (pyelonephritis) the former being usually a part of a septicemia 
but both possibly leading to what is known as " Surgical Kidney." 

Embolic suppurative nephritis arises from the lodging from the circu- 
lation of bacterial masses, usually the pyogenic cocci, in cases of septi- 
copyemia, as in puerperal infection, osteomyelitis, malignant endocarditis 
and the like. It is probable that the occurrence of such embolism implies 
a high virulence on the part of the germs or a large mass of them, other- 
wise one would expect focal or general glomerulonephritis. These emboli 
may either produce an infarct, when large enough to obstruct one of the 
vasa recta, or an obstruction of one of the small vessels to a tuft. Throm- 
bosis, hyaline or coagulation necrosis then occurs, about which polynu- 
clears accumulate and an abscess is rapidly formed. This causes degen- 
eration of the tufts and tubules supplied with blood by the vessel and of 
the tissues adjacent to the focus. Such abscesses may spread and nearby 
ones fuse forming large areas, at times occupying great parts of the organ 
or xiven its whole. In the case of infarction, coagulation necrosis usually 
follows and this may become purulent, an occurrence frequently suc- 
ceeded by penetration of the capsule and perinephric abscess, or on the 
other hand lateral spread through the organ; rarely sufficient reactive 
inflammation along the sides of the infarct limits it and inspissation of 
the pus occurs. The gross appearance of such an organ is little changed 
from the normal except in cases of infarction when the customary wedge- 
like pale area spreads in widening manner from the medulla to the cap- 
sule. On sectioning the disseminated variety, small yellow or gray spots 
or streaks surrounded by zones of congestion present themselves. Evi- 
dences of such a condition may of course show under the capsule when the 

49 



770 



A TEXT-BOOK OF PATBOLOGY 



Ascending 
succeeds upon 



lodgment of emboli chances to be near the surface. If pus has appeared 
the infiltrations will be soft or flow out as pus, and when many large foci 
have formed fluid pus is easily recognized. It has been stated that, when 
these abscesses occur chiefly or solely in the medulla, infection has arisen 
from bacteria in the course of their elimination through the renal tubules ; 
this may occur but direct hematogenic infection is certainly possible 
here as well as in the cortex. The functional pathology of this form of 
disease is usually so obscured by that of the original cause as to be indis- 
tinct. Since there is almost always a tubular as well as glomerular 
inflammation, the renal physiology will be modified to the extent of 
the lesions actually present. Urinary elimination is however always 
decreased and pus is found in the urine; the bacterial cause may some- 
times also be found there. The result of this disease when marked is 
commonly fatal unless it be amenable to surgery. Should recovery take 
place simple scar tissue would occur locally and destroy functional activity 
in such areas as were affected. But here again so much damage will have 
been done to glomeruli that in all probability, some general renal sclerosis 
will remain. 

suppurative nephritis (pyelonephritis, pyonephrosis) 
infection of the pelvis of the kidney or ureters, usually by 
infection ascending from the bladder 
or rectum, or the hilus of the kidney 
may be infected through the blood 
stream. In either case inflammation 
of the mucosa covering the pyramid 
spreads up the tubules by continuity 
along the epithelium, that is against 
the current, or penetrates to the sup- 
porting structures of the medulla 
and thus ascends. The bacteria 
principal^ responsible are the colon 
bacillus, Bacillus mucosus, strep- 
tococci and staphylococci. Acute 
cases or at least the acute stages, 
usually depend upon immediate simple bacterial infection while in the 
more chronic ones, associated with obstruction and purulent accummula- 
tions in the dilated calices, (pyonephrosis) a calculus is frequently an 
important predisposing factor. The course followed by the bacteria in 
ascending from lower in the abdomen has been variously explained but 
it seems today that they most probably enter the perivascular lymphatics 
of the ureteral wall or the pelvic areolar tissue and spread to the tissue 
about the renal pelvis. Their origin is a cystitis or periproctitis. In the 
former case they are assumed to penetrate the vesical mucosa to the 
periureteral lymphatics; if this occurs at the trigone the lesion may be 
bilateral. However possibly a superficial mucous membrane passage 
to the kidney is possible because pyelonephritis seems to occur in females 
at times without an antecedent cystitis. When vesical calculus exists, 
bilateral occurrence is common. The foregoing explanation of the 
genesis of this condition assumes an unobstructed ureter. Where any 
interruptions of the ureteral lumen or scaring of its walls exists, the 




Fig. 364. — Pyelonephritis, showing lines 
of ascending suppuration (Kaufmanh). 



DISEASES OF THE URINARY ORGANS 



771 



passage of bacteria to the pelvis is favored. As obstruction outside the 
bladder is usually unilateral, so in these cases, the pyelonephritis is 
unilateral. Grossly such an organ shows pale strands extending along 
the medullary striae from the pus-bathed pelvic mucosa; these seem to 
follow the course of the vessels, judging by their radiating course corre- 
sponding to the medullary branches and vasa recta and by the fine linear 
extensions to the capsule. In later stages these are found to be soft 
bands which may coalesce to form large areas giving way to definite 
abscesses of considerable size. These may rupture into the pelvis and 
be discharged, or if they penetrate the capsule, perinephric abscess results. 
Favorably ending cases are marked by cessation of activity and inspis- 
sation of the pus with the formation of a scar. Histologically the process 
is marked by polynuclear increase within and between the tubules while 
in addition there is practically always some degree of glomerulo-tubular 
nephritis. The function of the kidney is affected according to the extent 
of the lesions. In cases of involvement of nearly the whole organ, func- 
tion may cease entirely, while in mild or slow cases, little or no reduction 
may occur. The results of severe pyelonephritis are deformity of the 
organ and a diffuse nephritis. 

Renal Sclerosis. This name is applied to late or slowly progressive de- 
velopment of interstitial connective tissue overgrowth, replacing in part 
the term chronic interstitial nephritis but including types of change not 
primarily of inflammatory origin. The subdivisions discussed below are 
made partly upon pathological grounds but largely because it is necessary 
to separate some of them for clinical reasons. The processes are essen- 
tially those of chronic inflammation in some cases but replacement 
fibrosis following degenerations due to nutritional damage by blood vessel 
disease is a prominent feature. 

Sclerosis following acute interstitial nephritis is an irregular scar 
tissue formation in areas where, during acute or subacute infection, 
round cell infiltration has been succeeded by fibroblastic overgrowth. 
This is discussed under the heading of acute interstitial nephritis. It 
is not an important form, being met at autopsy as a delicate scarring or 
irregularity of the organ, and probably does not constitute a type of 
clinical significance. The functional pathology will only be affected if 
an acute or progressive glomerular lesion accompany or be implanted 
upon it. 

Sclerosis secondary to glomerular or diffuse nephritis has been 
discussed under the heading of glomerulonephritis but it is perhaps well 
to emphasize that it need not follow an acute attack but may arise at 
times insidiously over a period of months or years. It is the type of 
chronic nephritis commonly met with in young people or early middle 
life, but of course may occur at any age. It has been the custom to de- 
scribe two varieties of this kidney, one in which the glomerular lesions are 
combined with fibrous tissue overgrowth, red kidney, the other in which 
tubular degenerations are succeeded by interstitial hyperplasia, white 
kidney. Pure examples of both of these forms are rare, because a 
single kind of change is seldom dominant but since these terms remain 
in use in many quarters and since kidneys corresponding to these gross 
descriptions are occasionally seen, we shall discuss them from this 



772 



A TEXT-BOOK OF PATHOLOGY' 



standpoint and see how they fit into the present classification. A 
kidney the seat of the glomerular and interstitial change is usually 
smaller than normal, of mottled red color, with uneven or granular 
surface, and a tight capsule. The section surface reveals a cortex of 
irregular width with a loss of linear markings, although fine red 
streaks here and on the surface indicate attempts at regenera- 
tion. Histologically the picture is that in the last stage of glomerulo- 
nephritis with desquamation of epithelia, crescents within the glomerular 
space, tube casts, obliteration of tufts with hyalinization of the 
connective tissue in and about them, irregular distortion of many 
tubules, atrophy and disappearance of others. Obliterating endoangitis 
or hyaline change in the media of vessels may be seen in this form of 
nephritis. When regeneration has been active or hemorrhages have 
left pigmentation, this kidney may remain of normal or large size for 
some time, "the large red kidney" until the stage of secondary atrophy 
produces " small red kidney." In the last the organ is knobby, the 
capsule closely adherent, strands of pale color course irregularly over the 
surface and across the cut plane, separating islands of remaining func- 
tionating parenchyma. Under the microscope great atrophy appears, 
because everywhere connective tissue surrounds and distorts tubules. 
A small number of whole glomeruli may be seen but nearly all of them are 
replaced by hyaline. 

In those organs where the most prominent change is at first paren- 
chymatous swelling succeeded by interstitial overgrowth the latter 
grows in bands irregularly through the organ but is less visibly prominent 
because the secreting epithelium is swollen and degenerating and the 
whole organ is pale. In early chronic nephritis of this kind one sees the 
"large white kidney," a large, rather doughy, smooth organ from which 
the capsule may be removed with a little difficulty but, until secondary 
contraction and considerable union of it and the intrarenal fibers have 
occurred, without tearing the surface. Under the microscope the 
tubules are wide and show advanced degeneration with flattened frayed 
epithelia, casts, loose lining cells and mononuclears in the lumen; amyloid 
may be laid down in tufts or tubules. Atrophy of the parenchyma 
results from continuous cellular degeneration or pressure by constrict- 
ing fibrous tissue. Grossly this produces a contracted knobby organ of 
mottled pale color with an irregular but usually narrow cortex traversed 
by bands of glistening connective tissue. In both types cysts may result 
from obstruction to tubules. The fat of the pelvis is apt to be dispro- 
portionately increased and surround the calices. 

Primary simple or benign arteriolar sclerosis is the slow over- 
growth of connective tissue due to malnutrition from moderate grades 
of arteriocapillary fibrosis, rather widely distributed over the kidney 
but not at first combined with serious damage to the secreting structures. 
The condition appears especially in the fourth and fifth and sixth de- 
cades of life and is associated with cardiovascular rather than renal 
symptoms. The kidney is of normal size or smaller, hard and usually 
presents a granular or smoothly lobulated, gray surface. The section 
surface resembles that of the secondarily contracted red kidney. Mi- 
croscopically there is intimal thickening and medial degeneration of the 



DISEASES OF THE URINARY ORGANS 773 

small arteries with wide hyaline capsules of Bowman but practically 
normal tufts; intertubular connective tissue is rather regularly increased 
but this is not so marked early as late or as in those cases of combined 
character (see below). This disease 
is characterized by extremely high 
blood pressure, and by a tendency to 
cardiac enlargement. The functional 
value of the kidney is little affected 
because the parenchyma is not greatly 
involved at least until very late. 
Uremia is rare while cardiac failure 
is the rule. Nitrogen retention is 
certainly not pronounced. The spe- 
cific gravity of the urine may be high, 
traces of albumin and a few casts are 
found. 

In cases of general arterosclerosis 
there are minor clinical evidences of 
renal involvement which may last for 
many years without seriously affecting 
the patient's health or may suddenly 
become prominent. These are in- 
stances Of Vascular disease in the Fig. 365.— Arteriosclerotic kidney. 

larger vessels of the kidney. Such 

an organ may be little altered or may be uneven, mottled red-brown, 
firm and resilient. Upon section the larger vessels will have wider 
walls than normal while the surface may be practically unchanged. 




Fig. 366. — Sclerosis of the simple variety: great increase of connective tissue around the 
glomeruli, renal tubules, and blood-vessels but functionating elements fairly good. 

In late changes the kidney becomes quite small, hard and pale. Should 
acute infection or intoxication come into play or if there had been a 
preexisting glomerulo-tubular change, the combination would then con- 




774 



A TEXT-BOOK OF PATHOLOGY 



stitute true Arteriosclerotic nephritis, a form in which involvement of 
glomeruli and tubules runs about parallel with interstitial and vascular 
change. In some of these cases, the vascular lesions predominate, in 
others the nephritic; in the latter the picture is that of profound renal 
insufficiency with added cardio- vascular symptoms. In any given case, 
even with the history available, it may be impossible from a pathological 




Fig. 367. — Periglomerular fibrosis (from a photograph by Dr. Wm. M. Gray). 

stand point to establish the order of the changes just mentioned, it 
being possible that they might all be independent and only coincident- 
ally combined. Perhaps the keynote in the advancement of benign 
renal sclerosis and arteriosclerotic nephritis is the deprivation of 
nourishment by arterial changes, one in a healthy organ, the other 



in a mildly diseased organ. When the larger vessels are involved 
the lesions are more irregularly distributed so that there will be 
irregular patches of sclerosis showing as bands of fibrous tissue run- 
ning through the organ to the capsule and depressions of the surface 
will correspond thereto. Parenchyma caught in such bands will be 
squeezed to atrophy, that in the borders will be distorted while that 




Fig. 369. — Blood-casts, composed 
wholly of red or white corpuscles, or 
hyaline substance covered with blood- 
corpuscles. 



Fig. 368. — Waxy hyaline casts. 



DISEASES OF THE URINARY ORGANS 



775 



between will either attempt regeneration or remain functionating as 
well as possible; degeneration may occur. Where the vessels all over 
the organ are involved the kidney is rather uniformly reduced in size, 
hard, surrounded by fat, which also invades the pelvis, covered by a 
thick capsule which is so tight that the surface is torn on its removal. 
The exposed exterior of the organ is mottled pink-gray, granular or 





mom-. \ :\ ?N ^< 

To. .oq \lv -\ 





Fig. 370. — A, Tube-casts, composed of uric-acid crystals. B, Granular and fatty casts 
and two compound granular cells. 

knobby. On section a narrow, (2-4 millimeter) irregular cortex is 
seen, beset with stiff walled vessels, while the normal structures 
have given way to great distortion. Cysts are commonly met, due to 
obstruction of discharging tubules, high in the cortex. Under mag- 
nifications the vessels are found to be the seat of all forms of degenerative 
medial and productive intimal changes, 
principally the former. The connective 
tissue is firm and hyaline, with occasionally 
round cell accumulations. The glomeruli 
show hyaline changes which seem to in- 
dicate intimal swelling and obliteration while 
the capsule is thickened by hyaline. The 
tuft is often at some place adherent to the 
capsule, the remaining space being filled with 
cells or hyaline coagulation. At times the 
growth and contraction of the capsule, with 
adhesions of the tuft, obliterates the whole 
space and precedes the destruction of the 
whoie formation. The tubules show irregu- 
lariltes of lumen, some compressed to 
extinction, others about normal, others 

widely dilated, covered with flat epithelium and often containing a hyaline 
material. 

These cases present high blood pressure, polyuria with low specific 
gravity, greatly impaired nitrogen elimination, varying chloride output 
and marked cardiac symptoms. They are usually associated with 
generalized arteriosclerosis so that coronary sclerosis, with angina, 
apoplexy and uremia are commonly encountered in such cases. 




Fig. 371. — Cylindroids: a 
and b, Cast-like forms; c, 
filamentous forms. 



776 



A TEXT-BOOK OF PATHOLOGY 



Simple senile atrophy may be considered as a form of sclerosis 
since with disappearance of tissue, fibrosis takes its place. However 
such a lesion without changes described under the last two headings 
must be rare and it seems to have no clinicopathological significance. 

ATROPHY AND HYPERTROPHY 

Atrophy of the kidney may be congenital (hypoplasia), or may 
occur in old age (senile atrophy) . In the latter case (sometimes called 
" senile nephritis") the kidney is small, hard, and usually darker in color 
than normal. The irregular atrophy of the parenchyma leads to insu- 
larities upon the surface of the organ. The capsule may be thickened, 
and not rarely the perirenal fat is abundant, and considerable fatty 
deposit occurs beneath the mucous membrane of the pelvis. 

Microscopically, the renal cells are small in size, somewhat dark 
and granular. They may disappear entirely from the tubules in places, 
and the intertubular tissue and the basement-membrane are corre- 
spondingly thickened. The Malpighian bodies may be converted into 
contracted fibrous areas. 

Hypertrophy may affect one kidney when its fellow is congenitally 
wanting, has become diseased, or has been removed. Under these cir- 
cumstances the remaining or healthy organ sometimes undergoes con- 
siderable hypertrophy. The appearance is that of a much enlarged 
but otherwise normal kidney. 

Microscopically, there may be simply increase of the size of the 
tubules, or in cases in which the compensatory hypertrophy has begun 
before the completion of development there may be actual increase in 
the number of tubules and Malpighian bodies. 

DEGENERATIONS 
Parenchymatous degeneration, or cloudy swelling, occurs in the 
kidneys in consequence of the action of various poisons, infectious or 




Fig. 372. — Parenchymatous degeneration of the kidney, from a case of cholera (modified 

from Kast and Rumpel). 

chemical. It is met with in practically all cases of diphtheria, scarlet 
fever, and cholera, and less commonly in many other infectious dis- 
eases. Among the poisons the various parenchyma poisons (q. v., Part I) 
are all capable of attacking the kidney and producing cloudy swelling. 



DISEASES OF THE URINARY ORGANS 



777 



In case of either toxic or infectious degenerations, however, the process 
is prone to become more serious and to terminate in. acute tubular 
nephritis. No sharp dividing-line can be drawn between the two 
conditions. 

The kidney is somewhat increased in. size, is softer than normal, 
and, on section, the cortex is yellowish or of light grayish color (Fig. 372). 
The Malpighian bodies may be prominent as red spots lying in the light- 
colored renal tissue. The pyramids are often congested and contrast 
strongly with the cortical substance. 

Microscopically, fine granulation of the cells of the convoluted 
or other tubules is the striking feature. The nuclei of the cells are ob- 
scured, and at times all of the cells of the tubules apparently become 
fused. Exudative changes and hyperplasia of the interstitial tissues 
are wanting in a purely degenerative condition. Frequently the kidney 
is restored to the normal condition, but, on the other hand, acute Bright 's 
disease or fatty degeneration may ensue. 

Fatty Degeneration. — This occurs in consequence of the last- 
described condition, or independently in consequence of general anemia 
and systemic disorders, as in progressive pernicious anemia and tuber- 
culosis. Fatty degeneration of the kidney frequently occurs in the 
course of pregnancy, when it is due to disturbance of the circulation 
in the kidneys or possibly to obstruction of the ureters. In these cases 
the process usually advances to the condition of diffuse nephritis. 

In pure fatty degeneration the kidney is about the normal size, 
or often smaller than normal; is soft; and, on section, the cortex has 
about the normal width. The color is uniformly yellowish or mottled, 
certain areas being yellowish in color and others normal or perhaps 
hyperemic. Usually the surface of the kidney is smooth, but some- 
times localized spots of degeneration may become depressed and give 
rise to irregularities. 

Microscopically, the epithelial cells are granular or filled with oil- 
drops. The first appearance of these globules is near the basement 
membrane but later the whole cell is involved. Not rarely the cells 
are loosened and lie free within the lumen of the tubules. The 
basement-membrane and interstitial tissues may be somewhat thickened, 
either apparently or actually. 

Fatty I nfil tration is an unimportant condition. In the atrophic kid- 
neys of old age and in the contracted kidneys of chronic nephritis fatty 
infiltration of the areolar tissue beneath the mucosa of the pelvis is 
frequently observed. Fatty infiltration of .the epithelial cells may 
occur under normal conditions, or in cases in which the blood is sur- 
charged with fat (lipemid) and in which the kidneys are actively en- 
gaged in its excretion. Fatty infiltration of the perirenal cellular tissues 
occurs in general obesity, and sometimes as a localized affection in 
cases of advanced renal disease, particularly atrophy. 

Calcification may occur in diseased areas of the kidneys, as in 
degenerated and fibrosed areas, in old infarcts, and the like. Occa- 
sionally calcifications occurs in the epithelial cells themselves, particu- 
larly in such as have undergone necrosis. This is particularly marked 
in certain poisonings (e. g., mercuric-chlorid-poisoning) . Calcium salts 



778 



A TEXT-BOOK OF PATHOLOGY 



are sometimes deposited in infarct arrangement in certain diseases of 
the skeleton, notably osteomalacia. This is a part of the so-called 
calcium metastasis. 

Calcareous bodies in the cortex of the kidney are not infrequent. They 
are due to calcification of little cysts springing from the uriniferous 
tubules or Malpighian bodies. 

Glycogenic infiltration of the kidneys occurs in diabetes. It affects 
the epithelial cells, particularly those in the . portions of the oigan lying 
at the junction of the medulla and the cortex. The kidney is usually 
increased in size, the cortex broader than normal, and the consistency 
increased. The substance may be lighter colored and of homogeneous 
appearance. Microscopically, the epithelial cells, particularly those of 
the tubes of Henle, are found to be altered in character, the normal 
granular condition of the protoplasm having disappeared. The glyco- 
genic nature of the infiltrating substances is recognized by the dark- 
brown color obtained by staining fresh sections with iodin. 

Amyloid infiltration occurs in the kidneys under the same condi- 
tions as in the liver and spleen. It is most frequent in cases of chronic 
tuberculosis of the lungs, and occurs in casss of long-standing suppura- 
tion connected with bone, in syphilis, and as a result of other cachexias. 
The kidney is enlarged, sometimes to twice its normal bulk, is harder 
than normal, and, on section, the substance is found light grayish in 
color. It may be uniformly grayish or waxy; or, on the other hand, 
it may be mottled, grayish areas alternating with portions of yellow 
color, the latter being due to fatty degeneration. Amyloid deposit be- 
gins in the small blood-vessels, particularly those of the Malpighian 
tufts, spreads to the connective tissues of the organ, and it may be laid 
down under the epithelium of the tubules. 

Microscopically, the glomeruli may present spots of hyaline or homo- 
geneous appearance in which the capillaries seem completely disorgan- 
ized, and the entire glomerulus may be transformed into a transparent 
or translucent mass (Plate 16). The capsule is thickened and of ttimes 
simultaneously diseased. The tubules habitually contain hyaline casts. 
The organ becomes more or less anemic from obstruction of the capil- 
laries, and sooner or later fatty degeneration of the epithelial cells takes 
place. Inflammatory processes are usually wanting, but nephritis may 
become associated with amyloid degeneration, and the latter process may 
occur in kidneys primarily the seat of nephritis. Litten finds that the 
glomeruli are not always the first part affected; neither is the muscularis 
of blood-vessels always the etarting-point. The adventitia or intima may 
be first affected. He distinguishes the following varieties of amyloid 
kidney: (a) Pure amyloid kidney with amyloid change of the blood- 
vessels and with or without fatty change in the epithelium. Macro- 
scopically, the kidney may seem to be normal, but the iodin reaction 
indicates its true condition, (b) Large white amyloid kidney. This is 
the commonest form, and consists of amyloid degeneration plus chronic 
nephritis, (c) Amyloid contracted kidney is comparatively rare, and 
a very rare form is (d), the association of acute nephritis with amyloid 
change in the blood-vessels. 

The urine in amyloid disease is albuminous and scanty; the pro- 



PLATE 16 




Amyloid infiltration of capillary walls in kidney glomerulus. 



DISEASES OF THE URINARY ORGANS 



779 



portion of serum-globulin is excessive. Not rarely it contains hyaline 
casts which respond more or less distinctly to the color-tests for amyloid 
substance, but these are not diagnostic, and it is doubtful whether they 
are, in reality, composed of amyloid material. Functional activity 
is usually of the type seen in tubular disease. Increased blood pressure 
and cardiac hypertrophy seem not to occur. 

CONCRETIONS IN THE URINIFEROUS TUBULES 

Various calcareous concretions, or "infarcts," occur in the uriniferous 
tubules, particularly in the large collecting tubules near their termina- 
tion at the apex of the pyramids. Collections of urates, particularly 
urate of ammonium, are frequently seen in the form of radiating lines of 
light grayish, yellowish, or reddish color, marking the pyramids near 
the apices in newborn infants. These consist of crystalline concretions 
rilling the large uriniferous tubules, and have been considered as a valu- 
able medicolegal indication that the infant had breathed. They are not, 
however, sufficient proof. Sometimes the concretions are passed with 
the urine, and are discovered as large casts of conglomerated crystals. 
Less frequently other forms of crystals are met with in the infarcts of 
the newborn. Similar concretions occur in gouty individuals, particu- 
larly in aged persons, and calcium salts may be deposited when the 
blood is surcharged with them in consequence of diseases of the bones. 
Triple phosphates may be found as a consequence of obstruction of the 
urinary passages and stagnation of urine. 

Concretions composed of bilirubin may be formed in extreme jaun- 
dice, and particularly in the jaundice of the newborn. Infarcts com- 
posed of hemoglobin may be seen in cases of hemoglobinuria due to 
infectious and toxic causes. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the kidney in the form of minute, grayish- 
white miliary tubercles as part of a general hematogenous tuberculosis. 
A second form, which is also hematogenic., is known as chronic local 
tuberculosis. In this form the substance of the kidney near the cortex, 
or sometimes that adjacent to the pelvis, is occupied by masses of cheesy 
tuberculous tissue, and there may be secondary miliary tuberculosis 
near by. Softening is prone to occur, and the tuberculous focus may dis- 
charge into the pelvis of the kidney, leaving a necrotic cavity. The 
entire organ may be honey-combed with cavities. Tuberculosis of the 
kidney may also result from ascending infection, being secondary to 
tuberculosis of the seminal vesicles, of the bladder, of the ureters, and of 
the pelvis of the kidney. The process first involves the discharging 
tubules at the apices of the pyramids and spreads outward toward the 
cortex. Cheesy foci are formed, which may soften and discharge into 
the pelvis, as in the case of chronic local tuberculosis of the kidney. Oc- 
casionally the process seems to recede and tend to heal, the pelvic and 
abscess walls being encrusted with lime salts; along with any marked 
grade of renal tuberculosis there is usually an interstitial neuphritis with 
amyloid. It is difficult to determine whether tuberculosis of the kidneys 
is more frequently the result of urogenital tuberculosis primarily affecting 



780 



A TEXT-BOOK OF PATHOLOGY 



the parts below, or the cause of the latter. Primary affection of the 
kidney is certainly more common than many have been disposed to admit. 

Syphilis. — In the earlier stages of syphilis there may possibly be 
acute nephritis similar to that of other infectious diseases. Syphilis 
of long duration may lead to amyloid degeneration of the kidney or to 
chronic diffuse nephritis. Thickening of the blood-bessels is con- 
spicuous. In the latter case contractions of fibrous tissue leading to 
marked lobulation are rather characteristic. Syphilitic gummata are 
rare, but have been met with, and in their healing lead to marked scar 
formation. 

Lesions of leprosy, actinomycosis, and glanders have been observed. 



Fig. 373. — Tuberculosis of kidney (from the Vienna General Hospital Collection). 



Fibromata and lipomata may occasionally be met with in the 
kidney in the form of small rounded nodules. In association with 
calculous pyelitis and other conditions of the kidney leading to atrophy, 
the fatty tissue surrounding the kidney may be increased to such an 
extent as to constitute practically a fatty tumor. 

Leiomyoma is an occasional growth of the kidney. 

The most important tumors of the kidney are classified nowadays 
under the teratomata; they are the hypernephroma or Grawitz tumor, 
and the adenosarcoma or Wilm's tumor. 

Hypernephroma. — Under the name of struma aberrata suprarena- 
lis or hypernephroma, has been described a form of tumor of the kidney 
which results (Grawitz) from splitting off of a remnant of the supra- 
renal capsule and its incorporation in the kidney, where it subsequently 
grows (Figs. 374, 375). Wilson would explain these tumors as remains 
of the primary kidney tubules, nephrogenic tissue in the Wolffian duct. 
Dunn has found abnormal epithelial structures frequently in the kidney. 
These consist of suprarenal rests, adenopapillary tissue, and papuliferous 




TUMORS 



DISEASES OF THE URINARY ORGANS 



781 



cysts. This finding would help explain the variations seen in Grawitz's 
hypernephroma, since some are distinctly adrenal in character, while 
others show architectural features of carcinomata. The tumor presents 
the appearance of a small lipomatous yellow growth beneath the capsule 




Fig. 374. — Hypernephroma of kidney, showing destruction of most of the kidney sub- 
stance. The tumor was yellow in color (from a specimen in the collection of Dr. Allen 
J. Smith). 

of • the kidney, or more rarely, it may attain considerable size. Histo- 
logicall} r , it consists of epithelial cells arranged in tubules similar to those 
of 'the cortical portion of the suprarenal capsule. The characteristic 




Fig. 375. — Finer structure of the adenomatous form of hypernephroma. 

of the cells is their vacuolization, due to fatty or glycogenic infiltration. 
The supporting tissue is scanty, blood vessels are small; the cells near 
the septa are rather better preserved, that is less vacuolated, than 
in the center of nests or tubules. The growths that show the most 



782 



A TEXT-BOOK OF PATHOLOGY 



malignant characters are apt to contain giant cells and to resemble simple 
carcinoma. A hemorrhagic tendency is evidenced by many of these 
growths; when this occurs it may be apparent in the urine or it may 
produce mottled reddish pigmented tumors. 




Fig. 376. — Primary sarcoma of the kidney. 



Hypernephroma is very prone to invade the renal vein by extension; 
secondary growths appear most often in the lungs, bones and the opposite 
kidney. Epinephrin does not occur in hypernephromata, a fact consis- 
tent with the theory that they arise from tissue related to the suprarenal 
cortex. 




Fig. 377. — Adenosarcoma or Wilm's tumor of kidney. 



Sarcoma of the kidney is a frequent malignant tumor. It may occur 
congenitally, usually as a teratoma or a mixed tumor, or as a simple 
form in later life. The size and general appearance vary considerably, 



DISEASES OF THE URINARY ORGANS 



783 



but for the most part the structure is soft and grayish or sometimes 
quite red. Extravasations of blood or hemorrhages into the tumor are 
not uncommon. There may be a distinct capsule or the growth may 
be an infiltrating one. Cystic softening is not infrequent (Fig. 376). 

Microscopically, the appearance varies considerably, and the growth 
may be composed of round cells, spindle cells, or cells of various shapes. 
Not rarely a certain number of striped muscle-fibers are found, and to 
such growths the term rhabdomyosarcoma has been applied. In other 
cases there may be embedded in the sarcomatous tissue glandular acini 
composed of cylindrical or irregular epithelium, and to such the name 
adenosarcoma (Wilm's tumor) is given (Fig. 377). Occasionally, myx- 
omatous tissue, smooth muscle-fibers, or even islets of cartilage are 
found. The multiform character of sarcoma of the kidney suggests an 
embryonal origin, and it is not unlikely that inclusions of the primitive 
Wolffian body are the starting-point of the disease. 

The sarcomata of adult life are usually round or spindle celled, 
but angiosarcomata have been seen. 

Adenoma of the kidney has come to be recognized as a not in- 
frequent new growth which can appear as a diffuse neoplasia, altering 
little if any the appearance of the organ, 
or as a well outlined, encapsulated mass. 
The origin is probably a developmental 
defect. Such tumors usually arise in the 
cortex and grow slowly. The simple or 
alveolar form retains in a manner the 
structure of the organ, with rather 
irregular polyhedral cells taking the 
place of the regular cuboidal epithelium, 
while the papillary adenoma shows 
branching sprouts from the acinus walls, 
covered by tall cells; the latter has been 
seen in a cystic form. These tumors 
strongly resemble carcinoma and may a£ 
times behave like it. Proliferative 
changes occasionally affect the urini- fig. 378.— Lymphoid infiltrations 

fei'OUS tubules in interstitial nephritis, between the renal tubules; from a 

and give rise to small areas resembling case of leukemia - 
adenoma. 

Carcinoma is a rare primary tumor of the kidney, and occurs in per- 
sons of advanced years. The growth begins in the cortical substance or in 
the medulla, and presents itself as a soft white or, in case of hemorrhage 
into it, red tumor. 

Microscopically, it is found to be a glandular carcinoma presenting 
acini composed of epithelial cells of various shapes. Metastasis is rare. 

Secondary Tumors. — Among the secondary tumors of the kidney 
are both sarcoma and carcinoma. 

In the same group may fee included the lymphomatous infiltrations 
of leukemia (Fig. 378). In this disease the kidney is often enlarged, and 
on section is found to be uniformly white or mottled in color, the light- 
colored areas representing masses of lymphoid cells. Most of these 




784 



A TEXT-BOOK OF PATHOLOGY 



have doubtless been deposited from the circulation, but there is also 
evidence of local multiplication. 

Cysts of the kidney are of various forms. In the course of chronic . 
nephritis, especially the interstitial form, cystic dilatations of the con- 
voluted tubules and Malpighian bodies are observed. These appear 
as small or large rounded bodies lying immediately beneath the capsule, 
and on section are found to contain serous liquid, or colloid material, 




Fig. 379. — Large retention cysts of kidney (from a specimen in the Museum of the Phila- 
delphia Hospital). 

the result of degeneration of the epithelial lining of the cyst. Some- 
times very large cysts of this character are met with in cases of nephritis 
or even in otherwise healthy kidneys (Fig. 379). Cysts observed in 
kidneys which show no other disease are probably due to undiscovered 
obstructions of the uriniferous tubules. 

Congenital cystic kidneys are of striking appearance. Usually both 
kidneys are affected, and are transformed into masses composed of in- 
numerable cysts varying in size from microscopical points to cavities 



DISEASES OF THE URINARY ORGANS 



785 



as large as a walnut (Fig. 380). On section, the cysts are found 
to be filled with clear urinous liquid or with colloid material, and be- 
tween them is a stroma of more or less firm fibrous tissue supporting 
blood vessels, while under the microscope the lining is seen to be a single 
row of flat epithelia. The pelvis of the kidney is usually preserved. 
These cysts are formed by dilatation of the uriniferous tubules and Mal- 
pighian bodies, probably as the result of some fetal disease which causes 
obstruction of the tubules at their outlet at the apex of the pyramids, or 




Fig. 380. — Congenital cystic kidney. 

in consequence of faulty union between the upper and the lower segments 
of the uriniferous tubules in the development of the organ. Similar 
cystic degeneration, with enlargement of one or both kidneys, may occur 
in later life. Such cystic kidneys have their origin in congenital con- 
ditions, even though the enlargement does not take place until middle 
or more advanced age. Finally, cystic adenoma may again be mentioned. 

PARASITES 

Bacteria occur in the kidney in various affections: thus pneumococci, 
typhoid bacilli, and the bacilli of glanders and anthrax have been 
repeatedly demonstrated. In pyelonephritis the Bacillus coli communis 
is probably the usual active etiological agent. Streptococci occur in the 
nephritis of septic conditions and in primary infectious nephritis* of 

50 



786 



A TEXT-BOOK OF PATHOLOGY 



cryptogenic origin. Bacteria are occasionally found in the uriniferous 
tubules without gross lesions of the kidnej^ and are probably excreted 
with the urine. 

Animal parasites are occasionally observed, such as echinococcus 
cysts, filariae, the eggs of Fasciola hepatica, amebse, and infusoria. 
Round-worms and the oxyuris sometimes migrate into the bladder or 
enter through fistulse. 

The echinococcus cyst occurs in the form of hydatids, which may 
perforate into the pelvis of the kidney and discharge with the urine, or 
become inspissated and calcify. The Cysticercus cellulosce and Lingua- 
tula rhinaria are extremely rare. The Filaria bancrofti occurs in the 
lymphatic spaces and in the blood-vessels of the kidney in cases of 
filariasis with chyluria. The kidneys in these cases show a waxy appear- 
ance on section, especially toward the apices of the pyramids, and the 
surface of the kidney may be abnormally lobulated. Microscopically, 
the lymphatic spaces about the uriniferous tubules are greatly distended. 

The Schistosoma hematobium occasionally produces pyelitis and pye- 
lonephritis, with enlargement of the pelvis of the kidney. 

The Pelvis of the Kidney and Ureter 

congenital and acquired malformations 

Occasionally the pelvis or ureters, or both, may be absent or im- 
perfectly developed. Complete obliteration of the ureter may be ob- 
served. More frequently there are two pelves or ureters, and when this is 
the case the malformation is, as a rule, bilateral. 

Obstructions of the ureter may be due to twists, to congenital atresia, 
or to other diseases of the ureter, particularly at its entrance into the 
bladder. It may be brought about by the lodgment of renal calculi, by 
movable kidney, by tumors of the ureter, or by pressure upon it from 
without. The outflow of the urine may be obstructed by diseases of 
the bladder, and particularly by stricture of the ureter. 

Dilatation of the ureter results from the conditions just named 
and may be uniform or saccular. In the first case an increase of lumen, 
having a more or less constant size, develops as a result of obstruction 
at the vesical end. , The saccular variety is best shown as enlargement of 
the renal end when the pelvis dilates, but it may occur above one of the 
ureteral valves. The most important of such malformations arises as 
the result of obstruction to the urinary flow as hydronephrosis, a dilation 
of the upper end of the ureter and of the pelvis resulting in compression 
of the renal tissue with atrophy. When the obstruction giving rise to 
this is in the bladder, the effects are usually bilateral while a unilateral 
involvement is commonly produced by lesions above the bladder, most 
often pelvic stones. Whenever the flow is obstructed urine collects in 
the pelvis, presses upon the organ which at first enlarges and then atrophies. 
If the ureteral closure has been complete, sudden, and permanent, an 
acute stage of hydronephrosis is apt to form, shortly followed by atrophy 
of the kidney. If, however, obstruction to the urinary flow be incomplete 
or intermittent, there is a gradual increase in the size of the pelvis and 



DISEASES OF THE URINARY ORGANS 



787 



secondary renal atrophy. The first may be due to ligature in a surgical 
operation or to blocking by a stone, while the latter is the result most 
often seen with nephrolithiasis. Such an organ will show the pelvis widely 
dilated, containing a fluid of mixed urine and exudate. When stone 
is present, irregularity of the wall, plastic exudate or papillary growths 
may be seen. The renal tissue is compressed to a narrow band, with ir- 




is*: . -• . ' -. . -.^rG^r™" ' • ^ 

Fig. 381. — Hydronephrosis from vesical calculus. Note the hypertrophy of the bladder 
wall (case from the Children's Hospital). 

regularity, or even disappearance, of its striations, or the secreting tissue 
may be entirely absent, septa composed of vessels and their immediate 
supporting tissue remaining in the lobulated cystic organs. This dis- 
tention may be due entirely to stones, little fluid existing. In this case 
the caluli may mould themselves to the shape of the space, surround the 
calices and thus form budded masses or formations like antlers. When 
infection attacks such a process pyonephrosis, that is, suppurative 
pyelitis, occurs, and this may proceed to a pyelonephritis (q. v.). The 
kidney tries to functionate all the time, thus supplying the dilating 



788 



A TEXT-BOOK OF PATHOLOGY 



power, but as fibrotic atrophy gets under way this gradually diminishes 
to cessation. When these conditions are bilateral they are incompatible 
with life. 

CALCULUS 

Calculi are of frequent occurrence in the pelvis of the kidney, and are 
formed by the precipitation of various normal or abnormal constituents 




Fig. 382. — Calculi in the calices of the kidney; the renal substance is pressed upon so 
that atrophy has occurred (from the Vienna General Hospital Collection). 




Fig. 383. — Branched calculus of renal pelvis (from the Vienna General Hospital Collection). 

of the urine. There may be merely small gritty particles lying in the 
calices or in the pelvis, to which the term renal sand, or gravel, is given; 
or there may be large stones, almost filling the pelvis and calices, and 
forming more or less accurate moulds of these. The most frequent forms 
are those composed of uric acid and oxalate of lime, but phosphate and 



DISEASES OF THE URINARY ORGANS 



789 



carbonate of calcium and triple phosphate calculi are occasionally found. 
Stones composed of cystin and xanthin are rare. Uric-acid calculi are 
composed of the acid itself or of urates, and present themselves as yel- 
lowish, brownish or red, smooth, or somewhat irregular formations. 
Those composed of oxalate of lime are irregular in shape and of brownish 
or red color. 

The results of renal calculi may be trivial or serious. Small particles 
of renal sand are frequently passed without serious disturbance. Large 
calculi tend to set up inflammation of the pelvis of the kidney, and may 
obstruct the outflow of the urine, causing 
hydronephrosis (Fig. 384) . In some cases 
cancer seems dependent upon the continued 
irritation of a retained calculus. Those in 
the pelvis or ureter may pass down to the 
bladder, with the clinical picture of renal 
colic, or they may be caught in the ureter 
along its course or at the bladder opening. 
If caught, ureteritis or hydro-ureter may 
arise. In its passage the stone may so 
damage the ureter as to cause stricture. 

INFLAMMATION 

Inflammation of the pelvis, or 
pyelitis, may result from the irritation of 
poisons ingested, such as cantharides, tur- 
pentine, and the like, or it may occur in 
the course of infectious diseases of various 
kinds. More frequently it results from 
the irritation of a calculus, or from as- 
cending inflammation consequent upon 
cystitis and ureteritis. It is a common 
complication in pregnancy, a fact usually 
explained by the ease with which the 
bladder and ureters, congested by the 

obstruction to blood supply due to the large uterus, become infected 
through the short urethra. 

The organisms most often responsible are Bact. mucosum, Bact. Coli, 
staphylococci and streptococci. The infection passes upward by con- 
tinuity or along the ureteral lymphatics; a pericystitis and periure- 
teritis may also lead to a pyelitis. The mucous membrane becomes 
reddened and swollen, and' not rarely is marked with hemorrhagic ecchy- 
moses. The surface is covered with desquamated epithelium and pus- 
cells. The inflammation may extend to the substance of the kidney 
{pyelonephritis). Considerable purulent exudate may take place, par- 
ticularly when there is a calculus partially obstructing the ureter. When 
there, is complete obstruction the pelvis may become dilated with pus, 
and the calices or the entire kidney may be converted into a large pus- 
sac {pyonephrosis). In the chronic cases with no pus or no actively 
infectious organism, the pelvic wall becomes irregularly thickened, even 




Fig. 384. — Calculus in upper 
part of ureter and pelvis of 
kidney. 



790 



A TEXT-BOOK OF PATHOLOGY 



polypoid, or may show irregular granulation tissue, or again may be cov- 
ered with calcareous matter. Some form of atrophic nephritis is usually 
present. 

Inflammation of the ureter, or ureteritis, may occur under the 
same conditions as pyelitis. The mucous membrane of the ureter be- 
comes swollen and reddened, as in catarrhal inflammations elsewhere, and 
there may be erosions or superficial ulcerations. The other coats are 
thickened by inflammatory infiltration and, in chronic cases, by fibrous 
tissue overgrowth. 

INFECTIOUS DISEASES 

Tuberculosis of the pelvis of the kidney may occur as a miliary 
tuberculosis, or in the form of caseous nodules or masses. The latter 




Fig. 385.— Tuberculous pyelonephritis (modified from Bollinger). 

may be primary and hematogenous in origin, or may result from ascend- 
ing infection (Fig. 385). It seems from later observations that the 
tubercle bacillus passes up the unobstructed ureter by means of the 
lymphatics in the wall of this tube. When obstructed the passage of 
germs occurs by extension or aided by the changes in pre'ssure between 
the bladder and the pelvis because of the impeded downflow of urine 
through the ureter. 

In such instances the mucosa becomes more or less extensively infil- 
trated, and later caseous and ulcerated. The process extends to the 
calices, and subsequently to the pyramids and other parts of the substance 
of the kidneys. The pelvis may contain considerable quantities of 



DISEASES OF THE URINARY ORGANS 



791 



caseous or puriform matter, and the kidney substance may be extensively 
involved. The urine contains pus-corpuscles and often tubercle bacilli 
in great numbers. Tuberculosis of the ureters leads to nodular or dif- 
fuse thickening, and commonly to more or less obstruction (Fig. 386). 




Fig. 386. — Tuberculous nodule in the wall of the ureter, with beginning hydronephrosis 
(from a specimen in the Museum of the Philadelphia Hospital) . 

TUMORS 

Primary cancer is extremely rare. Secondary tumors usually come 
from one primarily in the urinary tract or wherever they can invade the 
lymph system of the pelvis. Small cystic formations are not uncom- 
monly seen in the mucous membranes of the ureters, and may be due to 
inflammatory obstruction of the crypts, to proliferation and softening of 
the lymphoid follicles, or to parasitic invasion (psorospermice) . 

PARASITES 

Round-worms have occasionally been found in the ureters. The 
eggs of Schistosoma hcematobium are frequently deposited in the mucous 
membrane, and occasion inflammation and papillomatous excrescences. 

The Urinary Bladder 

malformations 

Congenital malformations of the bladder are comparatively com- 
mon. Among the more important is exstrophy. The anterior wall of the 
abdomen and of the bladder being wanting, the mucous membrane, with 
the openings of the ureters, is exposed to view. Not uncommonly this 
condition is associated with epispadias, or division of the clitoris. Some- 
times the small intestine discharges through the exstrophic bladder, the 
large intestine being contracted or completely absent. 



792 A TEXT-BOOK OF PATHOLOGY 

Occasionally the urachus remains patulous in consequence of atre- 
sia of the neck of the bladder or urethra, and the urine is discharged from 
the umbilical end. In other cases the urachus is closed at either end and 
the intervening portion is dilated, with the formation of a cyst. Again, 
there may be only partial obliteration of the urachus, the remaining por- 
tion in connection with the bladder being patulous and greatly dilated, 
forming a congenital adventitious sac. In a case known by one of us 
this constituted a cavity of considerable size, and when filled distended 
the abdomen as far as the umbilicus. Congenital diverticula may occur 
in the anterior wall, and less commonly at the sides of the bladder. Com- 
plete absence of the bladder, division into lateral portions by a septum 
(vesica bipartitis), and other congenital defects are rare. 

Acquired Malformations.' — Dilatation of the bladder may result 
from congenital or acquired stenosis of its neck, or of the urethra; or 
from paralysis of its walls, in consequence of disease of the spinal cord 
or nerves. The organ may be greatly increased in size, often reaching 
the umbilicus. When the dilatation is acute the walls are greatly thinned, 
but when it has been gradually developed compensatory hypertrophy of 
the muscularis and of the submucous fibrous tissues leads to thickening 
of the walls (see Fig. 381). In these cases the mucous surface presents a 
ribbed appearance, fibrous-tissue bands standing out prominently and 
the mucosa being pouched between the bands. Diverticula of con- 
siderable size may form in this way, and the walls of the bladder some- 
times present a considerable number of pouches. False diverticula are 
occasionally observed, usually bulging out from the sides of the base of 
the organ, and arising as the result of weakening and rupture of the outer 
wall, the mucosa pushing out through such holes; dilatation and inflam- 
mation predispose to them while pericystitis may succeed upon them. 

CHANGES OF POSITION 

The position of the bladder, or of portions of it, is sometimes ab- 
normal. Thus, it may enter into a hernia, or a part of the wall of the 
bladder may prolapse with the wall of the vagina, forming vaginal cys- 
tocele. The latter is due to the traction of the prolapsing uterus or to 
repeated overdistention of the bladder, with weakness of the anterior 
vaginal wall. Complete inversion of the bladder through the urethra 
has been observed in women. 

RUPTURE 

Rupture of the bladder may be due to traumatism, and particularly 
to perforation by fractured pelvic bones. Rupture from overdisten- 
tion is rare. Occasionally it may result from abdominal compression 
when the bladder is distended with urine, and ulcerative processes be- 
ginning in the mucous membrane may perforate the wall, or phleg- 
monous inflammations or degenerating new growths surrounding the 
bladder may lead to perforation. In women perforations are frequently 
established between the bladder and vagina in consequence of pressure 
of the fetal head or of forceps, and vesicovaginal fistula results. Per- 
foration into the peritoneal cavity is usually followed by fatal acute 
peritonitis. Rupture into the tissues below the peritoneal reflections 



DISEASES OF THE UKINARY ORGANS 



793 



gives rise to widespread infiltration of urine and phlegmonous or gan- 
grenous inflammation. 

CIRCULATORY DISTURBANCES 

Active hyperemia may result from irritant poisons, such as can- 
tharides, or may occur in persons suffering from paraplegia, in conse- 
quence of disturbances of innervation or, possibly, by high acidity of 
the urine. 

Passive hyperemia occurs when there is pressure upon the inferior 
vena cava or thrombosis of that vein. The mucous membrane becomes 
dark red and is often marked with punctate hemorrhages. Consider- 
able varicosity of the veins at the neck of the organ may occur, and may 
give rise to edema, to copious hemorrhages, or to obstruction and reten- 
tion of the urine. 

Hemorrhages in the mucous membrane occur in severe congestion 
or inflammation, and in various hemorrhagic diseases. Large hemor- 
rhages into the cavity itself may result from traumatism from without 
or from calculi. The varicosities before mentioned may occasion con- 
siderable hemorrhage, as may also papillomatous or other new growths. 
Large quantities of blood with little admixture of urine may lead to the 
formation of dense clots within the organ, but when the quantity is 
small the blood is mingled with the urine. 

INFLAMMATION 

Inflammation of the bladder, or cystitis, varies in extent, dura- 
tion, and character. Acute cystitis may result from irritant poisons ex- 
creted with the urine from infectious processes extending from the 
renal pelvis or ureter, and frequently attends acute infectious diseases. 
In these cases, however, the disease is generally mild. More intense 
forms occur from extension of inflammation to the bladder in cases of 
urethritis, or when septic material is introduced in catheterization. 
Retention and decomposition of the urine from strictures or prostatic 
hypertrophy are frequent causes of chronic cystitis. The most common 
organisms in cystitis are micrococci and colon bacilli. These organisms 
may ascend the urethra, descend from the ureter, or extend throuhg the 
neck of the bladder from its related glands. The urine is usually alkaline 
except in cases of colon bacillus infection, when acidity is the rule. 

Cystitis may present itself as a mucopurulent catarrh, acute or 
chronic in course; as phlegmonous inflammation; or as a pseudomem- 
branous process. 

Mucopurulent cystitis in the acute stages causes swelling of the 
mucous membrane, with injection of blood-vessels and sometimes 
punctate hemorrhages. The surface, especially at the base, is covered 
with mucopurulent exudate of a tenacious character, in which pus- 
cells and desquamated epithelium are abundant, which objects, together 
with bacteria, red blood-cells and crystals, are found in the ammoniacal 
urine. 

In chronic cases thickening of the submucosa and hypertrophy of 
the muscularis cause great thickening of the organ, and the surface 



794 A TEXT-BOOK OF PATHOLOGY 

within is usually ribbed from the prominence of the fibrous-tissue bands 
and the pouching of the mucous membrane between the bands (Fig. 387). 
Erosion and ulceration may occur upon the surface, and occasionally 
perforation of the walls takes place. Incrustations of triple phosphate 
and of other common salts frequently cover the surface. 

Phlegmonous cystitis results from intense infections; it frequently oc- 
curs in the flabby bladder of paraplegia when there is retention of urine. 
The superficial parts of the mucosa may present a dry brown or gray 
appearance or the greenish appearance of gangrene; the involved areas 
slough off and appear in the urine. The submucous tissue is considerably 
swollen and infiltrated, and complete perforation of the walls and para- 
cystitis or phlegmonous inflammation of the tissues surrounding the 

bladder may ensue. Because the deep 
parts of the vesical wall are involved, 
it is easier for infection to reach 
the periureteral lymphatics since the 
ureter passes obliquely through the 
muscularis and submucosa quite a 
distance before reaching the mucosa. 
Pyelitis is more apt to follow this 
than other forms of acute cystitis. 

Pseudomembranous cystitis oc- 
curs in certain severe infectious dis- 
eases, and may present itself in the 
form of a typical pseudomembrane, or 
as a combination of phlegmonous and 
pseudomembranous inflammation. 
Beneath the false membrane the 
mucosa is usually definitely ulcerated 
and from such areas sharp hemor- 
rhages are apt to occur when the cover- 
. ing separates. Occasionally, pseudomembranes are formed without any 
inflammatory process in nervous individuals, and in the course of or after 
pneumonia a cast of the entire bladder of this nature has been seen by one 
of the authors. 

Chronic cystitis may follow an acute attack or be primarily a pro- 
gressive process; it practically always accompanies calculi. There is 
either a hypertrophy of the mucosa, with irregular papillomatoid out- 
growth, or a thinning of the layer by atrophy, depending upon whether 
the inflammation has weakened the musculature or not. With calculi, 
the wall is usually thickened and rugous. The secretion varies, but it is 
usually mucopurulent and covers closely the variegated or uniformly 
slate-colored mucosa. This color is due to altered blood-pigment. The 
muscular coat undergoes fibrous thickening and the contractility is 
impaired. Cystic formations, arising from degeneration of the epithelium 
just under the surface, have been observed, while on the other hand the 
transitional bladder cells may become keratinized forming irregular pale, 
glistening plaques. Malakaplakia is a condition of uncertain nature 
appearing as isolated, varying sized but small excrescences of yellowish 
color and a congested circumference. The essential cell is a large round 




Fig. 387.— Dilated ribbed bladder. 



DISEASES OF THE URINARY ORGANS 



795 



body with inclusions of various objects, red blood cells, bacteria and so 
forth. The lesion may ulcerate, or upon its removal an ulcer is exposed. 

INFECTIOUS DISEASES 

Tuberculosis of the bladder is usually secondary to tuberculosis 
of the kidney, or to that of the prostate, seminal vesicles, or epididymis. 
Tuberculous ulcers independent of tuberculosis elsewhere in the uro- 
genital tract may occur in phthisis or intestinal tuberculosis, but such 
cases are rare. The lesions observed in tuberculosis of the bladder are 
ulcerations, beginning in mucosa and submucosa, miliary tubercles for 
the most part occupying the base of the organ and surrounding the 
orifices of the ureters, and there may be distinct or clustered tubercles. 




Fig. 388. — Tuberculosis of the bladder (Orth). 



Numerous small ulcers or a single large ulcerated surface may be ob- 
served (Fig. 388). Deposits of triple phosphate frequently form incrus- 
tations on the surface. 

Syphilitic ulcers and gummata have been observed in the bladder, 
but are extremely rare. 

CALCULI AND FOREIGN BODIES 

The bladder is the commonest seat of urinary calculi. They may 
occur in the form of fine particles or gravel, or as stones of considerable 
size. Usually there is but one; sometimes a considerable number may 
be present. The shape and general appearance depend upon the com- 
position of the stone. 

The formation of calculi is explained by precipitation of inorganic 
matter from supersaturated urine even in the absence of inflammatory 
products, or by changes in reaction due to fermentation. The former 



796 



A TEXT-BOOK OF PATHOLOGY 



usually gives rise to uric acid, oxalate and phosphate stones while triple 
phosphate and urate concretions arise from the latter (AschofT). How- 
ever, the presence of exudative substances like fibrin may form a starting 
place for precipitation although such a nucleus is often not discoverable; 
perhaps it disintegrates after the salts are deposited. Foreign bodies 
may occasionally form the nuclei of stones, and thus a calculus in the 
bladder may form around broken portions of catheters, hairpins, or other 
foreign bodies inserted into the urethra. Similarly, parasites may be the 
nucleus, or mucus or degenerated epithelial cells constitute the focus about 
which the deposit occurs. Catarrhal conditions of the bladder, especially 




Fig. 389. — Multiple calculi of kidney (From " Surgical Diseases and Injuries of the 
Genito-Urinary Organs" by J. W. Thomson Walker). 

when combined with stagnation of the urine as the result of hyper- 
trophy of the prostate, urethral stricture, and the like, are the most 
common antecedent causes. The nucleus being present it attracts 
mucus and other organic matter; this forms a matrix upon which lamellae 
of salts are deposited, probably in some chemical combination with the 
organic matter since they are not found in their ordinary crystalline 
forms. 

Calculi in the bladder may be composed of uric acid or urates, of 
oxalate of lime, of various phosphates, of carbonate of lime, or of certain 
organic compounds. 

Uric acid and urate calculi are less common in the bladder than in 
the kidney. They result from surcharge of the urine with uric acid in 
lithemic or gouty individuals, and from acid decomposition rendering 



DISEASES OF THE URINARY ORGANS 



797 



the uric and urates insoluble. Uric acid calculi are yellowish or red in 
color, rounded, slightly granular or smooth upon the surface, and, as a 
rale, quite hard. The calculi composed of urates are usually more 
irregular and softer, and are generally lighter in color. Frequently 
phosphates are combined with them. These stones may be started in the 
kidney pelvis, especially in the young, and there assume somewhat the 
shape of the kidney hilus. 

Phosphatic calculi may be of several kinds: they may be com- 
posed of phosphate of lime, triple phosphate, or mixed phosphates. 
They form the most frequent variety of calculi and concretions in the 
bladder, and are generally due to alkaline decomposition causing a de- 
posit of the simple phosphate of lime or of the combination of phosphate 
of magnesium with ammonium phosphate, known as triple phosphate. 
These deposits may occur in the form of incrustations upon the surface 
of the bladder in various diseases, or in the form of irregular, soft, and 
more or less white calculi. 

Oxalate of lime occasions rounded, hard calculi, of brownish color 
and of irregular, granular surface, from which they derive the name 
mulberry calculi and because of which they frequently give rise to bleeding. 
They occur in conditions similar to those causing uric-acid stones which 
substance may be included in them. 

Calculi composed of calcium carbonate give the impression of being 
made of groups of smaller stones although they are smooth, pale and 
compact; a few are lamellated. Xanthin stones are exceedingly rare but 
are easily recognized by their cinnabar red color. Stones composed of 
cystin, indigo and calcium sulphate are reported. 

Results of Urinary Calculi. — While cystitis and retention of urine 
favor calculus formation, the latter is prone to occasion increased irrita- 
tion and inflammation, and may cause serious obstruction to the outflow 
of urine, and thus retention in the bladder. Ulceration may take place, 
and perforation of the bladder-walls may ensue. Hyertrophy of the 
walls occurs when the stone only partially obstructs the outflow, and 
under the same conditions the ureters may become distended and hydro- 
nephrosis may occur. Not rarely the stone lies in a pouched dila- 
tation of the wall of'the bladder, either from having been formed in that 
situation in consequence of stagnation of the urine, or from having 
caused a dilatation by weakening the walls at a certain point. Complete 
encapsulation of the stone has been observed in such cases. 

Various objects are found as foreign bodies in the bladder. They 
include most commonly the products of inflammation higher up, such 
as casts or tissue cells, but bodies are sometimes introduced through 
the urethra. Hairpins, tooth-brushes, matches, etc., have been found. 
Occasionally parasites are found in the bladder (filarise and distoma). 

TUMORS 

Polypoid outgrowths from the mucosa may be observed in chronic 
cystitis. 

Papillomata occur either as the result of chronic irritation or as 
apparently causeless tumors. The papilloma presents itself as a some- 
what cauliflower-like elevation affecting the base, and sometimes con- 



798 



A TEXT-BOOK OF PATHOLOGY 




Fig. 390. — Tuft of papilloma of the bladder. 




Fig. 391. — A, Epitheliomatous tumor; B, wart-like growths; C, villous growths (Clado) 



DISEASES OF THE URINARY ORGANS 



799 



siderable portions of the mucosa, and has a whitish or grayish color. 
It is usually vascular and, therefore, frequently occasions hemorrhages. 

Microscopically, it is composed of a delicate connective-tissue stroma 
containing large, thin-walled blood-vessels, and covered with cylindrical 
epithelium (Fig. 390). Occasionally papillomata become transformed 
into malignant epitheliomatous growths. 

Carcinoma is a rare form of primary tumor. It occurs as a some- 
what papillomatous thickening of the mucosa, or as a more considerable 
infiltration of the wall of the bladder (Fig. 391). Microscopically, it is 
composed of large polymorphous epithelial cells infiltrating the walls 
more or less deeply and irregularly, or arranged in acini or alveolar 
formations. 

Secondary carcinoma of the bladder may result from extension of 
prostatic or uterine cancer. Very rarely the bladder is involved by 
metastasis. 

Fibroma, fibro=adenoma, rhabdomyoma, and myxoma are 

occasionally observed, while mixed tumors of certainly teratomatous 
origin have been seen. Cysts may be formed by closure of pouched 
diverticuli or by distention of the patulous urachus. Cysts of obscure 
origin are sometimes met with; dermoid cysts are rare. Sarcoma is very 
rare. 

ABNORMAL CONDITIONS OF THE URINE 1 

Quantity. — The normal quantity in the adult is from 1500 to 2000 
c.c. Conditions which check the perspiration or action of the bowels 
increase the amount of urine; excessive sweating and diarrhea have the 
reverse effect. In the latter case the excretion may be almost sup- 
pressed (anuria). The same may occur in acute nephritis or chronic 
nephritis with uremia, in extreme anemia, and in acute or chronic 
obstructive conditions in the gastro-intestinal tract interfering with 
absorption of water. Occasionally, anuria is reflex, resulting from 
obstruction of the urinary passages by calculi. The quantity of urine 
is increased (polyuria) in cases of excessive consumption of water, and 
habitually in diabetes mellitus and insipidus and in chronic nephritis. 
The amount of urine is also influenced by the blood-pressure ; increased 
flow follows high arterial pressure, while decrease follows low arterial and 
high venous pressures. 

Specific Gravity. — Normally the specific gravity is 1015 to 1020. 
It becomes increased when the amount of urine is decreased, and vice 
versa. The specific gravity is especially high in diabetes mellitus, 
despite the polyuria, sometimes reaching 1040 or 1050. It is low in 
most forms of chronic nephritis, in diabetes insipidus or simple polyuria, 
and in anemia and hysteria, or other nervous diseases. 

Color. — The normal amber color is due to the presence of various 
pigments, especially urobilin and uro-erythrin. These are derivatives 
of hemoglobin or bilirubin. 

In pathological conditions other pigments, such as hematopor- 
phyrih, pathological urobilin, melanin, etc., are met with. Indican 

1 See Physiology of Kidney, page 760. 



800 



A TEXT-BOOK OF PATHOLOGY 



is present in the urine in the form of a chromogen, which may 
sometimes become oxidized, with the formation of dark-colored pig- 
ment-animal-indigo. Certain drugs eliminated with the urine cause dis- 
colorations. Bilirubin occurs in jaundice and other conditions, and 
blood or hemoglobin may cause discoloration. 

Reaction. — Normally, animals upon a diet composed largely of 
protein excrete an acid urine because of the sulphuric and phosphoric 
acids formed in the metabolism of this food. A high percentage of 
carbohydrate ingested results in alkalinity since polybasic acids are 
produced, from which alkaline carbonates are oxidized. After a meal, 
protein-eating animals may have an alkaline urine, probably because 
acid is being used in digestion. Decomposition of the urine usually 
causes an intense alkaline reaction by conversion of the urea into am- 
monia. 

Qlucosuria is a term applied to the presence of glucose or grape- 
sugar in the urine. The condition is discussed in the chapter on Dis- 
orders of Metabolism. 

Levulosuria may be associated with glycosuria or be alimentary in 
origin; lactosuria is met in nursing women, in certain gastro-intestinal 
diseases of childhood and as an alimentary incontinence. 

Pentosuria is a condition in which pentoses, sugars containing five 
atoms of carbon in each molecule, appear in the urine. The condition is 
important mainly because pentoses react to certain reduction tests 
(Fehling's, Trommer's) like glucose. They do not polarize light nor 
ferment as does glucose. Pentosuria is a metabolic disorder of uncertain 
character sometimes occurring independently, sometimes in association 
with diabetes. It is not the result of disordered metabolism of starches, 
and the source of the pentoses is uncertain, though it is not improbable 
that they are derived from nucleoproteins of various organs; being there- 
fore endogenous, since they may be excreted in quantity greater than 
present in the food, and such patients seem to have a tolerance to the 
ingestion of pentose. It may occur as an alimentary affair when the 
diet contains much of this sugar. 

Alkaptonuria is a metabolic disturbance in which the urine turns 
black after excretion. The addition of alkalies to the fresh urine causes 
immediate change to a dark or black appearance. The chemical sub- 
stances concerned in this phenomenon are homogentisic acid and some- 
times uroleucinic acid, aromatic acids derived from protein metabolism. 
These substances are in part derivatives of albumins of the food, but 
always also in part the products of metabolic destruction of tissue pro- 
teins. Their appearance in the urine has been ascribed to the lack 
of ferments which normally destroy these substances. It has also been 
held that homogentisic acid is formed in the intestines by bacterial proc- 
esses involving decomposition of tyrosin. Clinically, alkaptonuria 
has been found associated with diabetes, tuberculosis, and pyonephrosis. 
In a number of cases of alkaptonuria there has been found the peculiar 
black pigmentation of cartilages called by Virchow ochronosis. This at 
times affects superficial cartilages like those of the ear, where it causes 
visible discoloration. Besides alkaptonuria, chronic phenol-poisoning 
may also occasion ochronosis. 



DISEASES OF THE URINARY ORGANS 



801 



Choluria is the name indicating the presence of biliary pigments 
and acids in the urine. It is most frequently observed in cases of jaundice 
due to hepatic disease, but may also occur in so-called hematogenous 
jaundice, the formation of the pigment in some of the latter cases prob- 
ably taking place in the kidneys themselves. The urine presents a dark 
color, varying from brownish to greenish. Oxidizing substances, such as 
fuming nitric acid, produce a play of colors. 

Microscopically, the cellular constituents of the urine are found 
stained, and granular concretions of bilirubin or rhombic crystals may 
be observed. Hyaline casts, more or less deeply stained by the pigment, 
are frequently seen. 

Urobilinuria. — Urobilin occurs in the normal urine mainly as a 
chromogen, or is converted into urobilin on the addition of acid. Some- 
times urobilin is present in large quantities in the fresh urine. This 
has been particularly observed in fevers, in jaundice, and in certain 
anemic diseases, especially in pernicious anemia. Its presence in large 
quantities is due to damage to the liver parenchyma. 

Indicanuria. — Indigo-blue occurs in the urine as a chromogen 
which gives rise to the formation of indigo on decomposition. This 
indican, or indoxyl sulphate, is a product of indol derived from the in- 
testine, and an excess of indican in the urine is significant of intestinal 
decomposition. 

Other forms of the ether-sulphuric-acid series occur in the urine, but 
are less significant. 

Acetonuria occurs to a slight extent in health, but more particu- 
larly in conditions of inanition, in gastro-intestinal disturbances, and 
in fever. It is especially significant in diabetes mellitus, and may become 
very pronounced toward the latter end of this affection. 

Diaceturia, or the condition in which diacetic acid appears in the 
urine, is also met with in fevers and inanition, but particularly in diabetes. 

Hydrothionuria refers to the presence of sulphuretted hydrogen 
in the urine. This is noted occasionally in auto-intoxications or as the 
result of fermentative changes in the urine. The urine may have a 
foamy appearance, to which the term pneumaturia is sometimes applied. 
Other gases may be present, but only in small proportion and rarely. 

Melanuria is a term applied to the dark discoloration of the urine 
occasionally seen in persons suffering from pigmented tumors. It also 
occurs in phthisis and other wasting diseases. As a rule, the urine be- 
comes darker after addition of oxidizing substances, but it may be quite 
dark when passed. 

Albuminuria. — Minute traces of serum-albumin probably occur in 
the normal urine. The term " albuminuria," however, is applied to cases 
in which albumin is readily detected. It may be accidental — that is, 
dependent upon the admixture of albuminous substances from the 
mucous membrane lining the urinary passages — or essentially renal in 
character. In the former instances the presence of abundant blood- or 
pus-cells indicates the nature of the case. True renal albuminuria con- 
sists of the excretion with the urine of serum-albumin and serum-globulin, 
the former being considerably more abundant than the latter. Pure 
serumuria is extremely rare, and pure globulinuria perhaps even more so. 
51 



802 



A TEXT-BOOK OF PATHOLOGY 



Albuminuria is more frequently the product of actual renal disease 
or nephritis, and is then due to the disease of the epithelium of the 
glomeruli and tubules. A certain amount of albumin occurs in de- 
generative or congested conditions of the kidneys; in various general 
diseases affecting the blood without manifest disease of the kidney, 
such as anemias, diabetes, toxemias, arid the like; in certain nervous 
affections probably influencing the circulation; and in disorders of the 
digestive tract. 

At times albuminuria is periodic or cyclic, this periodicity depend- 
ing upon general conditions, such as diet, exposure, and exercise, which, 
in turn, affect the blood or renal circulation. Considerable amounts of 
albumin in the urine are never physiological. Large proportions of 
globulin occur in amyloid disease of the kidneys. 

Orthostatic albuminuria is a form, as yet not satisfactorily explained, 
that appears when certain individuals occupy the upright posture, or 
some unusual position, for a prolonged period. It seems as if the cir- 
culation of the kidney were in some way at fault for lordosis has been 
observed in many cases. Familial traits, a weak constitution and 
anemia are often combined with it. Casts are not usually found. 

Albumosuria. — Various albuminous substances derived from serum- 
albumin or serum-globulin, and not coagulable by heat, occur in the 
urine. These are hydration products designated albumoses or pro- 
pepton. True pepton has never been found in the urine. Albumo- 
suria occurs in cases in which pus-cells or large exudates are undergoing 
absorption, as in septic processes, pneumonia, and the like (pyogenic 
albumosuria). In another group of cases intestinal malassimilation or 
decomposition comes into play (enterogenic albumosuria). In the third 
group diseases of the blood, such as leukemia and various intoxications, 
are active (hematogenic albumosuria). A fourth, or puerperal, form 
occurs after labor. In the " albumosuria " of Bence- Jones, which accom- 
panies myelomata, the abnormal substance is probably not an albumose, 
but a globulin produced by the tumor cells or during their disintegration. 

Nucleo=albuminuria. — Nucleo-albumin, formerly supposed to be 
mucin, is derived from the protoplasm of the surface epithelium of the 
urinary tract, and occurs in the urine in small quantity in nearly all 
persons, and in large quantity when there is irritation of the lining 
mucosa, particularly in pyelitis and cystitis. 

Cystinuria is a disorder of metabolism in which cystin, a nitrogenous 
sulphur compound, appears in the urine. Cystin is a normal inter- 
mediary product of metabolism which is further oxidized and, there- 
fore, does not appear in the urine. In cystinuria there is a retardation 
or absence of this oxidation. In some cases diamin, putrescin, and 
cadaverin have been found associated with cystin. This appears to 
represent an advanced grade of the same metabolic disturbance. Cysti- 
nuria may occasion no symptoms; but sometimes cystin calculi are 
formed in the kidney or bladder. 

Fibrinuria occurs in conditions in which lymph or blood gains ac- 
cess to the urinary passages. Fibrinous casts or shreds may be passed, 
or small flocculent particles are observed. Fibrinuria is usually asso- 
ciated with hematuria or chyluria. 



DISEASES OF THE URINARY ORGANS 



803 



Hematuria is a term applied to the presence of blood in the urine. 
This may be accidental from admixture of menstrual blood and the 
like, or may be a pathological condition, in which the blood originates 
from the kidneys, ureters, bladder, urethra, or other parts of the urinary 
system. Renal hematuria may result from intense congestion or from 
hemorrhagic nephritis. Traumatism, either from without or from 
calculi in the pelvis, is a frequent cause. Tumors and specific inflamma- 
tory processes are occasional causes. Sometimes hematuria is due to 
intense anemia, hemorrhagic diseases, or severe intoxications. Hema- 
turia which is due to admixture of blood with the urine below the kidney 
results from traumatism, injury by calculi or catheterization, from 
vascular tumors, and occasionally from inflammatory or other disease 
processes. (See also essential hematuria, page 755.) 

Renal hematuria is distinguished from that originating in the bladder 
by the intimate admixture of urine and blood, and by the associated 
evidences of renal disease — renal epithelium, tube-casts, etc. Fragmen- 
tation of the red corpuscles is said to indicate renal hematuria. In 
hematuria originating in the bladder larger clots may pass, in associa- 
tion with bladder epithelium and mucin (nucleo-albumin) . In cases of 
sudden ,renal hemorrhage large clots, sometimes forming casts of the 
pelvis, may be formed and discharged. 

Hemoglobinuria indicates the presence of free hemoglobin or of 
methemoglobin in the urine, without the presence of blood-corpuscles. 
Hemoglobinuria results from causes which lead to disorganization of 
blood and elimination of the coloring-matter through the kidneys. It 
is met with in various infectious diseases, such as malaria, and in in- 
toxications, as in poisoning with potassium chlorate, carbolic acid, 
arsenic, and other drugs, or with toadstools. It occasionally results 
from snakebite or poisoning by other venomous animals. 

Paroxysmal hemoglobinuria is a form of intermittent disease espe- 
cially frequent in subtropical countries. The attacks sometimes seem 
to be determined by exposure to cold and other external influences, 
while the predisposition may be dependent upon syphilis or other general 
disorders. It seems to depend upon the existence in the body of an 
autohemolysin which becomes active only at temperatures lower than 
normal; there is usually a hemoglobinemia in association with it. The 
urine presents a dark-red or brownish color, and when tested with the 
spectroscope shows the bands indicative of hemoglobin or methemoglobin. 

Microscopically, the hemoglobin may present itself in the form of 
granules or cast-like formations, or sometimes as crystals. Blood- 
corpuscles are absent or, at most, present in extremely small numbers. 

Lipuria. — A small amount of fat may appear in the urine in cases 
of advanced diffuse nephritis with fatty degeneration, and in certain 
cases of pyelitis. In other cases lipuria results from disorders in which 
there is excess of fat in the blood (lipemia). This occurs in cases of ex- 
cessive consumption of oil or fatty food and in cases of intoxication, 
notably by arsenic. It is sometimes present in diabetes, phthisis, 
chronic alcoholism, and obesity, and fractures injuring the marrow or 
serious traumatism of the subcutaneous fatty tissues may cause fat 
embolism and lipuria. 



804 



A TEXT-BOOK OF PATHOLOGY 



The appearance of the urine varies with the amount of fat, but, 
as a rule, there is a solid scum upon the surface, and there may be large 
oil-drops. Occasionally the urine is quite milky when recently passed. 
Microscopically, oil-drops are more or less abundant, and fat-crystals 
may be discovered. 

Chyluria is the name applied to a milky condition of the urine 
which probably results from admixture of lymph or chyle. The urine 
is light colored, and more or less milky in appearance. Often there is a 
reddish discoloration from associated hematuria (hemato chyluria) . The 
urine contains albumin and sometimes albumoses. 

Microscopically, numerous oil-drops of varying size and, usually, 
blood-corpuscles are detected. The most frequent cause is the obstruc- 
tion of the lymphatic channels and their subsequent rupture in the 
kidney or bladder in consequence of the lodgment of the Filaria san- 
guinis hominis. In these cases the embryos of the filarise are usually 
detected in the urine. Sometimes a chyluria is non-parasitic, but the 
causes are obscure. 

Bacteriuria. — Normally, the urine contains no bacteria. In cases 
of cystitis or other inflammatory diseases, however, and particularly 
when catheterization has been practised, bacteria of decomposition 
may be present, such as the Micrococcus urece, Bacterium termo, the Bacil- 
lus proteus, yeast fungi, and other forms. Not rarely the Bacillus coli 
communis is met with, particularly in ascending infections of the urinary 
tract. In cases of certain infectious diseases, such as typhoid fever, 
pneumonia, and erysipelas, the specific micro-organisms may be found 
in the urine, having escaped from the blood through the capillaries of 
the glomeruli. Streptococci are also met with in primary and secondary 
infectious nephritis. Pseudodiphtheria bacilli are so common upon 
the genitalia and in the urethra that it is usual to find them in voided 
urine. The tubercle bacillus may be discovered in cases of tuberculosis 
of the kidney, ureters, bladder, or other parts of the urinary tract. It is 
frequently present in clusters, this constituting a marked point of dis- 
tinction from the smegma bacillus, which is often found in urine, espe- 
cially that of women, and is easily mistaken for the tubercle bacillus. 
Another point of distinction is the greater ease with which the smegma 
bacillus, stained with carbolfuchsin, may be decolorized by alcohol. 
Positive differentiation in doubtful cases is made by injection of the 
urine into guinea-pigs. 

CHEMICAL CHANGES AND SEDIMENTS 

The various inorganic and organic constituents of the urine may 
be present in excessive quantities, and may form deposits, or abnormal 
chemical substances may be detected. 

Uric acid is deposited in the form of yellowish, brownish, or reddish 
crystals of whetstone shape, or as irregular angular formations super- 
imposed or clustered together (Fig. 392). The color is due to uro-ery- 
thrin taken up from the urine. The crystals of uric acid may deposit 
from a highly acid urine, even though there be no excess. 

Oxalate of lime occurs in the form of highly refracting octahedral 
corpuscles, their appearance being likened to that of an envelope (Fig. 



DISEASES OF THE URINARY ORGANS . 805 

393). Certain foods rich in oxalates may cause excessive excretion, 
and oxaluria occurs as an independent condition of obscure nature 
allied to gout and lithemia. Oxalates deposit from highly acid urine, 
even though no excess be present. This must be distinguished from 
oxaluria proper. 




Fig. 392. — Various forms of uric acid Fig. 393. — Various forms of crystals 

■ crystals. of oxalate of calcium. 



Phosphates. — Various forms of phosphates are found in crystalline 
form in urinary sediments. Basic phosphate of magnesium and neutral 
phosphate of lime are found in urine becoming alkaline, while the phos- 
phate of ammonium and magnesium, or triple phosphate, is met with 
when alkaline decomposition takes place. It presents itself in different 
forms, the most characteristic being the large coffin-lid crystals and 
certain star-shaped formations (Fig. 394). Triple phosphate is espe- 
cially abundant in cystitis with alkaline decomposition of the urine in 
the bladder. 




Fig. 394. — Crystals of triple Fig. 395. — Urate of ammonium 

phosphate (ammonium-magnesium crystals, 
phosphate) . 



Urates are deposited from acid urines as a whitish or reddish sedi- 
ment of amorphous character. The reddish color sometimes observed 
is due to admixture of urinary pigment. In decomposing urine, of 
somewhat alkaline reaction, urate of ammonium is deposited as hedgehog 
crystals or masses (Fig. 395). 



806 



A TEXT-BOOK OF PATHOLOGY 



Hippuric acid is rarely met with, excepting after the ingestion of 
benzoic acid or of certain fruits. It forms long, prismatic crystals, which 
occur in groups. 

Carbonates and sulphates are rarely observed in urinary sediments. 

Fat=crystals occur in the form of fine needles, or of aggregations 
arranged in a star-like manner and resembling tyrosin groups (Fig. 397) . 
They are found in cases of chronic nephritis, pyelitis, and cystitis. 

Tyrosin. — This substance usually occurs in the urine in solution, 
or rarely in the form of sheaves composed of fine needles arranged in 
star-like clusters (Fig. 396). 

Leucin occurs as small spheres, often having a somewhat radiated 
structure within. These are most readily discovered when the urine 
has been partially evaporated. 

Leucin and tyrosin are observed in acute yellow atrophy of the liver, 
in phosphorus-poisoning, and occasionally in severe infectious fevers. 






Fig. 396. — Leucin spheres and tyrosin 
needles. 



Fig. 397. — Cholesterin plates and fat- 
crystals (needles). 



Cystin occurs in the form of hexagonal plates often superimposed. 
They are most frequently associated with cystin calculi in the kidney. 

Xanthin is extremely rare, but may be associated with xanthin 
calculus. 

Cholesterin appears in the form of flat, quadrilateral plates, with 
a re-entering angle at one of the corners (Fig. 397) . They are met with 
in old cystitis or pyelitis, but are rare. 

Indigo. — Amorphous particles or crystals of indigo may be found 
in urine containing great excess of indoxyl sulphate. They present a 
characteristic bluish color. 

Bilirubin, hemoglobin, methemoglobin, and hematoidin are 
occasionally seen as brownish granular concretions or in the form of 
rhombical crystals. (See Chyluria, Hemoglobinuria.) 

THE URETHRA 

CONGENITAL ABNORMALITIES 

Absence of the urethra is sometimes met with in association with 
other defects of development. Partial deficiencies and abnormal struc- 
ture of the urethra are more frequent. Thus in the female it may be 
reduced in length and open in the anterior wall of the vagina, and in the 



DISEASES OF THE URINARY ORGANS 



807 



male may terminate at the base of the scrotum. Obliteration of part of 
the urethra (atresia) may occur in cases of defective development of the 
corpus spongiosum; more commonly there is obliteration of the meatus. 
Other abnormal conditions will be considered in connection with defective 
development of the penis. 

INFLAMMATIONS 

Inflammation of the urethra, or urethritis, is most frequently due 
to a specific micro-organism — the gonococcus of Neisser. Some cases, 
however, are non-specific, resulting from irritation by chemical or me- 
chanical agents with associated infection (staphylococci, streptococci, 
or other organisms). Some of these cases are caused by direct trauma- 
tism, as by blows, injuries caused by catheterization, and the like; 
in other cases foreign bodies, as calculi, become lodged in the urethra 




Fig. 398. — Acute urethritis, showing purulent infiltration and gonococci in the cells and 
between the cells (Birch-Hirschfeld.) 

and occasion inflammation or injure the urethra in passing. Urethritis, 
like inflammations of other mucous membranes, may occur in various 
infectious diseases, such as typhoid fever, scarlet fever, small-pox, etc. 
In the female, inflammations of the vagina and vulva frequently ex- 
tend to the urethra. A form of pseudomembranous urethritis of obscure 
origin has been observed in a few cases. 

Specific urethritis, or gonorrhea, is always due to direct infection 
with the gonococcus (for description of the organism, see Part I). Cer- 
tain conditions of the urethra favor infection; thus an adherent prepuce, 
by causing greater retention of the infective matters, increases the 
liability, and probably congested and irritated states of the urethral 
mucosa heighten the susceptibility. The vulnerability of different indi- 
viduals probably varies; and doubtless the micro-organism has greater , 
virulence in some instances than in others. 



808 



A TEXT-BOOK OF PATHOLOGY 



Pathological Anatomy.- — Urethritis usually first affects the mucosa 
at or. near the meatus, but tends to spread rapidly to the posterior parts. 
The mucosa is at first intensely congested, red, and swollen. Soon a 
purulent exudate, of yellowish or greenish color, makes its appearance. The 
small crypts or lacuna? swell and become distended with purulent exudate. 

Microscopically, urethritis presents the features of an intense puru- 
lent catarrh. Within a few days of the onset the superficial epithelium 
becomes loosened and begins to desquamate; and at the same time 
polymorphonuclear leukocytes make their way to the surface between 
the epithelial cells. The pus-cells and epithelium of the surface exudate 
contain gonococci in abundance, and the organisms are discovered in the 
cells and to a less extent between the cells of the deeper layers of the 
mucosa (Fig. 398). The process extends most deeply in those parts of 
the urethra (penile portion) in which the lining epithelium is of the 
columnar variety. 

Associated Lesions. — In simple cases the disease proceeds no further 
than has been described, but after a period of several weeks gradually 
subsides. Very frequently, however, the inflammation extends in 
various directions, and complicating conditions arise. Sometimes the 
infective agents penetrate the membrana propria of the small glands 
(Littre's glands), or enter the submucosa by direct invasion through 
the interglandular parts of the mucosa. Leukocytic collections in the 
submucosa or periurethral abscesses may result. In these cases the 
gonococcus alone may be the infective cause, or other pyogenic organ- 
isms may be associated; sometimes periurethral lesions are caused by 
staphylococci independently of gonococci. Occasionally, accumulations 
of pus in Tyson's glands may simulate periurethral abscesses. In the 
female, similar purulent distention of the glands of Bartholin is a fre- 
quent lesion. The inflammation of the urethra is often confined to the 
anterior portion (anterior urethritis), but may extend to the posterior 
portion (posterior urethritis). In the male, secondary involvement of 
the prostate gland is likely to occur with posterior urethritis; and, more 
rarely, the organisms invade the vas deferens and find their way to the 
epididymis, causing acute epididymitis. The. bladder is rarely involved, 
the mucosa apparently offering considerable resistance to the infection. 
In the female, acute vaginitis, and especially inflammation of the cervix 
uteri, are commonly associated. Secondary extension to the uterus may 
occasion gonorrheal endometritis; more frequently the uterus is but little 
affected, while the Fallopian tubes suffer intense inflammation. Ca- 
tarrhal or purulent salpingitis, often complicated with local peritonitis, 
is one of the most important of the complications. When pus from a 
gonorrheal urethritis is brought in contact with the conjunctiva a severe 
form of purulent conjunctivitis results. 

Metastatic lesions are not infrequent. Among these, gonorrheal 
arthritis is the most familiar. It usually occurs late in the disease, some- 
times after an interval of weeks or months from the onset, and involves 
the larger joints (knee, elbow, wrist). Purulent exudation and fibrous 
ankylosis may result. A similar lesion is gonorrheal tenosynovitis. 
Sometimes the pericardium, endocardium, and myocardium are in- 
volved, and, more rarely, the pleura and the membranes of the cord. 



DISEASES OF THE UEINARY ORGANS 



809 



Enlargement of the lymphatic glands of the inguinal region (bubo) 
is frequent; sometimes it terminates in suppuration. 

Chronic urethritis is usually the result of continuation of the acute 
form. It may present itself in the form of a chronic catarrhal process, 
as a hyperplastic inflammation, or as a productive or cicatrizing form. 

In the catarrhal form of chronic urethritis the lesion is practically 
the same as in the acute disease. The epithelium is loosened and more 
or less desquamated, and sometimes distinct erosions are observed. 
Definite ulcerations may occur in parts back of strictures. The columnar 
epithelium may be converted into the squamous form diffusely or in 
localized areas. The crypts and glands of the mucosa may be distended 
with desquamated cells and more or less periglandular inflammation may 
be observed. 

In the hyperplastic variety the mucosa is thickened in a papilloma- 
tous manner, and diffuse catarrhal inflammation is associated. 

The productive or cicatrizing form is the most important. It may be 
diffuse in character, but is usually localized and leads to stricture 
formation. 

Stricture of the urethra is most frequent in the membranous por- 
tion, but may occur in the anterior parts. Not rarely there are several 
strictures in the course of the canal. Histologically, the stricture is the 
result of productive inflammation of the mucosa and submucosa. It is. 
therefore, a lesion of slow development, and may not become obstruc- 
tive for months or years after the acute attack of gonorrhea, to which 
it owes its origin, has subsided. The lumen of the urethra is encroached 
upon in limited area or for a considerable distance, and, on section, the 
stricture is found to be hard and resisting. When the lumen of the 
urethra is greatly narrowed the outflow of urine is impeded, and hyper- 
trophy of the walls of the bladder results. Later, dilatation of the 
bladder, and even of the ureters and pelvis of the kidneys, may result. 
The urethra back of the stricture frequently presents the lesions of 
chronic catarrhal or hyperplastic urethritis, the obstruction serving 
to prolong the original inflammation of these parts. Rupture of the 
urethra and extravasation of urine into the cellular tissues, with subse- 
quent necrosis and gangrene, may occur. 

In chronic urethritis there is usually a constant but slight dis- 
charge of mucous exudate (gleet). Examination of this may discover 
no gonococci or only an occasional group. The urine contains floccu- 
lent shreds (clap-threads), which on microscopical examination are 
found to be granular or homogeneous structures resembling cylindroids, 
and often covered with pus-cells that have adhered to the surface. The 
amount of discharge may be quite copious at times, especially in the 
hyperplastic and catarrhal forms of chronic urethritis. 

INJURIES OF THE URETHRA 

The urethra may be injured by traumatism from without or within. 
In cases of falls with injury of the perineum the membranous portion 
of the urethra may be seriously lacerated, and in women injuries sus- 
tained during labor may cause immediate rupture of the urethra, or may 
first occasion inflammatory and necrotic changes in the anterior wall 



810 



A TEXT-BOOK OF PATHOLOGY 



of the vagina and secondary perforation of the urethra. Injuries from 
within the urethra may be due to forced attempts at catheterization 
when some form of obstruction opposes the passage of the instrument. 
" False passages" are thus occasioned, and may result in fistulae and ex- 
travasations of urine. Concretions or calculi from the kidney or bladder 
may lodge in the urethra, and may cause immediate perforation or 
primary inflammation, with secondary rupture of the walls. 

Rupture of the urethra causes extravasation of urine into the peri- 
urethral cellular tissues. If the skin is intact and the urine cannot 
escape, widespread inflammation, necrosis, and gangrene are liable to 
occur. Fistulous communications may be established with the exterior, 
or, in women, with the vagina. 

INFECTIOUS DISEASES 

Gonorrheal urethritis is the important infectious disease of the 
urethra. For convenience it has been described under Inflammations. 

Tuberculosis of the vesical end of the urethra may be associated 
with tuberculosis of the bladder. Lupus sometimes involves the meatus 
and anterior end of the urethra in cases of lupus of the external geni- 
talia of women. Very rarely tuberculosis of papillary form is met with 
in the urethral mucosa. 

Syphilis. — The chancre may occur in anterior parts of the urethra 
in either sex. It usually undergoes rapid ulceration which on healing 
leaves a stricture. Mucous patches may occur within the meatus. 

TUMORS 

The urethra of women is more often the seat of tumors than is that 
of men. 

Small polypoid tumors are occasionally seen hanging from the 
meatus; they may be fibrous, villous papillomata, or glandular, the 
latter tending to become cystic. 

Carcinoma is usually secondary to cancer of the external genitalia 
(vulva, vagina, glans penis). Primary carcinoma originating from 
Cowper's gland has been described, and a few cases of carcinoma of 
other parts of the urethra have been observed. 

Cysts of the mucous membrane, due to retention of the contents 
of the small glands, are occasionally met with, especially in the posterior 
portion of the urethra. The inner lining of the cyst is elevated in the 
form of papillae covered with squamous epithelium. 

Sarcoma of the urethra has been described, but is very rare. 



CHAPTER VIII 



DISEASES OF THE REPRODUCTIVE ORGANS 
The Uterus 

Development and Anatomy. — The uterus is formed by the fusion 
of the middle portions of Muller's ducts, the fusion first occurring be- 
low where the cervix uteri is developed. The epithelial lining of the 
ducts gives rise to the mucosa of the uterus, and its outer layers, to the 
muscularis. The utricular glands are developed by ingrowths from the 
lining cells, and first appear and reach their most complex development 
in the cervical portion. The outer surface of the cervix (portio vaginalis) 
is lined with stratified squamous epithelium; the cavity of the uteru- 
and cervical canal, with cylindrical ciliated cells. In the cervical pors 
tion are found numerous racemose glands and between them simple 
tubular glands; in the corpus uteri the glands are simple tubules. 

CONGENITAL ABNORMALITIES 

Absence of the uterus is very rare. The organ, however, may be 
represented only by a mass of rudimentary tissue. Hypoplasia of the 
uterus may be a congenital condition, or may be the result of arrested 
development and the consequent failure to increase in size at the age 




Fig. 399. — Uterus bicornis unicollis (Winckel). ! 



of functional activity. The term uterus infantilis is applied. Stenosis 
and atresia of the uterus and vagina may be the result of disease or mal- 
developments, due to partial obliteration of Muller's ducts. 

Among the more striking malformations of the uterus are those which 
result from incomplete fusion of Muller's ducts. In normal develop- 
ment these ducts unite and fuse in the lower portion to form the uterus 
and vagina, but remain separated above, where they form Fallopian 
tubes. Among the anomalous conditions of the uterus are uterus 
bicornis, in which the cervical portion of the uterus is single and two 
entirely distinct uterine cornua are present (Fig. 399); uterus septus, 

811 



812 



A TEXT-BOOK OF PATHOLOGY 



in which the external appearance may be that of a single uterus, but on 
section a septum is discovered, which divides the organ into lateral 
halves (Fig. 400) ; uterus duplexus, in which there are two vaginas, two 
uteri, but only two fallopian tubes. The term uterus unicornis is used 
to designate cases in which but one of Muller's ducts has developed, 
the other remaining rudimentary. Malformations of the vagina may 



be associated with those of the uterus already named, though this is 
rarely the case. A number of subdivisions have been distinguished for 
each of these malformations, but they are unimportant. 



The normal position of the uterus is one of slight anteversion with 
anteflexion; that is, the fundus lies a little farther to the front than the 
cervix, and there is a slight bend or flexure in the middle portion. 

Anteflexion is a condition in which there is marked angulation of 
the uterus, the fundus falling forward. Shortness of the round ligaments 
predisposes to this condition; and it may be caused by the pressure of 
tumors situated posteriorly, by distention of the rectum with gas, by the 
traction of adhesions and by abnormal conditions of the uterus itself, 
causing a loss of tone in the walls. The grade of anteflexion varies 
greatly. Among the effects of this condition is interference with the 
discharge of menstrual blood, with consequent accumulation and in- 
tense dysmenorrhea. 

Anteversion, or the tilting forward of the uterus without abnormal 
angulation, occurs under similar conditions, but is less important. 

Retroflexion of the uterus occurs in cases in which the walls of the 
uterus are abnormally soft and have lost their tone. It may be caused 
by the pressure of tumors or the traction of adhesions. Sometimes it is 
due to habitual constipation, causing pressure upon the lower part of 
the uterus (cervix) by masses in the rectum; retroversion and subse- 
quently retroflexion are produced. Laxness of the vaginal walls and 
rupture of the perineum may cause this or other abnormal positions of 
the uterus by depriving the organ of its support from below and sub- 




Fig. 400. — Uterus septus (Cruveilhier). 



ALTERATIONS OF POSITION 



DISEASES OF THE REPRODUCTIVE ORGANS 



813 



jecting it to the unresisted pressure of the abdominal viscera. The 
degree of retroflexion varies from slight angulation to a complete back- 
ward doubling of the organ. The fundus may undergo considerable 
congestion from the interference with circulation, and it is not rarely 
enlarged. Adhesions between the uterus and rectum are frequent. 

Retroversion is the condition in which the position of the uterus 
is changed in relation to the pelvis and soft parts, with or without 
flexion or alteration in the angle of the various sections of the organ 
itself. The same causes are operative as for flexion, especially prominent 
being subinvolution. 

Lateral displacements of the uterus are rare, and are associated 
with adhesions or tumors operating laterally. 

Upward dislocation may be caused by pressure of tumors in the 
pelvis; it may be due to the traction of adhesions between the uterus and 
large tumors of the ovary. In such cases the uterus may be greatly 
stretched and the vagina may be similarly affected. 

Prolapse of the uterus is a term applied to descent or downward 
displacement. It is possible to distinguish any number of degrees of 
prolapse, but it is sufficient to speak of two only: incomplete prolapse. 




Fig. 401. — Complete prolapse of the uterus (Penrose). 



in which the os uteri is still within the vagina; and complete prolapse, 
(procidentia), in which it projects through the vulva, thus partially or 
wholly everting the vagina. The causes of prolapse of the uterus are 
numerous. Injuries to the perineal floor and unusual laxity of the vaginal 
walls or the ligaments of the uterus are very important. Traumatism and 
excessive pressure upon the uterus from the abdomen may cause descent 
of the organ, especially if laxity of the ligaments was present before. 
Retroversion also favors the descent by bringing the uterus into the 



814 



A TEXT-BOOK OF PATHOLOGY 



pelvic axis. Enlargement of the uterus itself may be the cause of pro- 
lapse, and in any case the organ usually becomes enlarged after the 
prolapse, in consequence of passive congestion. The cervix is gener- 
ally directed somewhat backward, and the mucous membrane fre- 
quently presents catarrhal inflammation and contains enlarged veins. 
The cavity may be filled with considerable mucous secretion. 

In some instances of apparent complete prolapse the fundus of the 
uterus may be but little displaced, the great descent of the os uteri in 
such instances being due to hypertrophic elongation of the vaginal portion 
of the cervix. 

In all cases of prolapse the anterior and posterior walls of the vagina 
are displaced downward more or less, and sometimes may be completely 
everted. The anterior vaginal e version may draw with it the posterior 
wall of the bladder, and cystocele results. Similarly, the posterior vag- 
inal wall may drag down the anterior wall of the rectum, and rectocele 
is produced (Fig. 401). 

Inversion of the uterus is a condition in which the organ is turned 
inside out to a greater or less extent. This condition is caused by traction 




Fig. 402. — Fibroid polyp, producing partial inversion of the uterus (Penrose). 

upon the placenta during rapid labor or in the presence of lax uterine 
muscle, when it is acutely developed; or by the similar traction of poly- 
poid submucous tumors, when it is more slowly formed (Fig. 402) . There 
may be only a slight inversion of the fundus, or the organ may be com- 
pletely inverted and may present itself through the vagina and vulva. 
This may be associated with partial or complete prolapse. Secondary 
changes are apt to occur in such cases. The mucous membrane suffers 
catarrhal inflammation with ulceration; and the entire uterus, though 
at first perhaps enlarged by congestion, subsequently atrophies. 



DISEASES OF THE REPRODUCTIVE ORGANS 



815 



STENOSIS, DILATATION, AND RUPTURE 

Stenosis of the uterine cavity may occur as a congenital condition, 
or may be acquired in cases in which inflammation has led to cicatricial 
stricture. There may be almost complete obliteration of the external 
or internal os uteri. 

Dilatation of the cavity of the uterus is a not infrequent result of 
stenosis. The dilated cavity may be filled with mucous or seromucous 
secretion from the non-menstruating mucous membrane (hydrometra), 
or with accumulations of menstrual blood (hematornetra) . Occasionally, 
in cases of hydrometra secondary decomposition of the liquid causes 
gas formation, and physometra results, or suppuration occurs (pyometra). 
In cases of hematornetra the amount of blood in the uterine cavity may 
be very considerable, and in some instances rupture of the wall of the 
uterus is the result. This may be simply due to the increasing pressure, 
or it may result from inflammation or ulceration at the point of stenosis. 

Rupture of the uterus may occur during pregnancy or labor; and 
occasionally at other times in consequence of inflammations, abscess, 
softened tumors, and the like. The rupture may involve the whole 
wall, splitting open the peritoneum, while in some cases the latter is intact 
but has a hematoma beneath it. There is, in the complete cases, a 
large amount of blood shed into the peritoneal cavity, the loss of which 
may bring on fatal shock. The commonest ruptures are, of course, 
those in and near the cervical part, but during severe labors, especially 
of the more difficult presentations, the musculature of the uterus may 
suffer a longitudinal rent. Disease of the muscle, deep penetration of the 
chorionic villi and faulty position of the uterus, which impedes its pro- 
pulsion of the fetus in the correct axis, favor rupture. When the break 
occurs at the fundus it is due to deep placental penetration or to scars or 
tumors. The most frequent and serious consequence of rupture is peri- 
tonitis. Occasionally, when rupture has occurred during pregnancy, the 
fetus may be enclosed in a sac formed by circumscribing peritonitis; the 
rupture may at the same time heal. 

Laceration of the cervix uteri is a very common accident of labor. 

CIRCULATORY DISTURBANCES 

Hyperemia of the uterus is a physiological condition during men- 
struation, and occurs in all forms of acute inflammation of the organ. 
There is no essential difference between menstrual hyperemia and that 
of pathological conditions. 

Menstruation is the discharges at monthly intervals of bloody fluid 
from the uterine body. Before the flow appears, perhaps as long as ten 
days, there is a marked widening of the uterine mucosa, due to increase 
in lymph, activity of glands and some congestion. In the depth of the 
membrane the glands show great tortuosity and overfilling with secretion, 
their supporting tissue being scanty. This stage resembles some forms 
of inflammation and should be remembered when examining morbid 
material. The more superficial layers are at first edematous, then 
become crowded with large pale cells. The surface is thrown into folds. 
Congestion increases as the time for the flow approaches, red blood cells 



816 



A TEXT-BOOK OF PATHOLOGY 



also leaving the capillaries and wandering through the interstices. They 
make their way to the surface and escape between the separated columnar 
epithelium or small groups of these cells may be shed to allow them to 
pass. When the flow is declining, the mucous membrane shrinks to its 
normal thickness, while epithelial regeneration replaces any lost tissue. 
The glands, which were swollen, hyperactive and variously distorted- in 
shape, return to their normal straight tubular appearance, the lumina 
being nearly closed. The uterus as a whole enlarges during the flow and 
becomes softer, a condition assumed to a less degree by the adnexa also. 

It is perhaps well to state that the uterine mucosa during the men- 
strual period reacts to a hormone elaborated in the ovary, wherein seems 
to reside the governing control of the uterus. Moreover the reaction, 
as viewed under the microscope, is akin to that seen after fecundation 
andjimplantation of the ovum, namely the true decidua. 

Abnormalities of this function are due to hypoplasia of ovary or 
uterus, to malpositions of the latter, natural or acquired, to physical 

obstruction to the outflow, but especially to 
various forms of inflammation. A very 
curious type of dysmenorrhea, the cause of 
which is not clearly understood, is called 
dysmenorrhea membranacea in which mem- 
branous formations are discharged from the 
uterus (Fig. 403) and in which there is severe 
pain. Cases of this character are particularly 
prone to occur when chronic inflammations 
of the mucosa have existed, and the affection 
is then termed endometritis exfoliativa. The 
discharged casts, more or less perfectly 
formed, resemble the decidua vera in simple 
cases while leucocytes, mono- and polynuclear 

Fig 403.— Membrane dis- U and fibrin are present when i n fl amma . 
charged in membranous dys- . . ,£,, 

menorrhea (Penrose). tion is coexistent. The picture may vary, 

however, from time to time in the same case. 
The epithelium covering the membrane resembles squamous variety of 
this cell. 

Passive hyperemia of the uterus occurs in conditions of general 
venous stasis, but especially when dislocations of the uterus cause 
pressure upon the venous plexuses. The organ is enlarged, the veins in 
the serous surface are prominent, the mucous membrane is dark red, 
and when the congestion is long continued chronic endometritis may 
result. 

Hemorrhages may occur into the uterine cavity, into the walls of the 
uterus, or into the peritoneum outside the uterus. Hemorrhages during 
menstruation and in labor are physiological forms. Pathological increase 
of menstrual hemorrhage is spoken of as menorrhagia, which may occur 
in certain general diseases, such as anemia, or in consequence of local 
conditions, notably tumors. Intense congestion of the organ from car- 
diac disease or from malpositions of the uterus may also lead to hemor- 
rhages during the menstrual period. Hemorrhages between the menstrual 
periods are spoken of as metrorrhagia. This may be caused by general 




DISEASES OF THE REPRODUCTIVE ORGANS 



817 



conditions, such as the hemorrhagic diseases and infections (small-pox, 
etc.), but it is especially frequent as a result of local diseases, of which 
fibroid tumors and cancer are the most important. There is a normal 
hemorrhage from the uterus after detachment of the placenta at par- 
turition which ceases upon uterine contraction, but which may continue 
in case of imperfect contraction, retained placenta, or diseased uterine 
vessels. 

Hemorrhages into the substance of the uterus are rare and are gen- 
erally due to traumatism. Apoplexy of the uterus is an interstitial 
hemorrhage due usually to arteriosclerosis with uterine atrophy. 

Hemorrhages into the peritoneal cavities or into the cellular tissues 
in the vicinity of the uterus are more frequent. Of the intraperitoneal 
hemorrhages, the most frequent is accumulation of blood in Douglas ; 
pouch (retro-uterine hematocele) . The blood in this case may come from 
various sources, such as ruptured ovarian follicles, ruptured tubes in 
tubal pregnancy, hematosalpinx, or rupture of varicose veins in the 
broad ligament. The blood may become absorbed without causing other 
pathological results, or it may set up inflammation and result in ad- 
hesions between the uterus and rectum. Not rarely, perforation with 
discharge of the blood through the rectum or vagina occurs. 

Hemorrhages into the vesico-uterine pouch and hematomata be- 
tween the layers of the broad ligament are rare. 

INFLAMMATIONS 

Inflammation may affect the mucous membrane of the uterus, 
when the term endometritis is applied; or the wall of the uterus, when 
it is termed metritis. The names perimetritis, indicating inflamma- 
tion of the peritoneal covering of the uterus, and parametritis, inflam- 
mation of the cellular tissues in the vicinity of the uterus, are unneces- 
sary, as these conditions are simply forms of local peritonitis. For 
purposes of convenience the inflammations of the uterus occurring dur- 
ing the puerperium will be separately considered. Some of the condi- 
tions here described as inflammatory are not positively of such nature, 
though no sharp line of division can be drawn between the inflammatory 
and the hyperplastic forms. 

Acute catarrhal endometritis may result from traumatism, or 
from infection with pyogenic organisms or gonococci. Occasionally 
it occurs as a complication of general infectious diseases, such as typhoid 
fever and cholera. The mucous membrane is swollen and intensely 
hyperemic; very often small hemorrhages are observed. Desquamation 
of the epithelial cells, with mucopurulent secretion, causes considerable 
discharge. Very intense forms may occasion necrosis of the epithelial 
cells and the formation of pseudomembranous deposits. This is par- 
ticularly frequent in the infectious diseases. 

Chronic endometritis may be the continuation of acute endometri- 
tis, and is especially apt to occur in persons of reduced vitality, such as 
scrofulous or chlorotic women, or in those in whom the circulation is 
sluggish. The influence of passive congestion has already been referred 
to. Very often the etiology is entirely obscure. 

The mucous membrane in the earlier stages is simply swollen, and 

52 



818 



A TEXT-BOOK OF PATHOLOGY 



produces abundant mucopurulent secretion. Later, hyperplastic 
changes occur, the hyperplasia affecting either the uterine glands or 
the interstitial tissue. The terms endometritis glandularis and endo- 
metritis inter stitialis have been applied to distinguish these varieties. 




Fig. 404. — Glandular activity in menstruation and mild endometritis. 

In the former, microscopical examination shows an abundance of pro- 
liferated glandular acini extending through the depth of the mucous 
membrane (Fig. 404) but not into the muscle. In the latter the glands 
are less conspicuous, but round-cell infiltration and abundant connective- 




Fig. 405. — Diffuse endometritis. 



tissue hyperplasia between the glands are conspicuous features (Fig. 
405). In some cases of the glandular form, the process seems more 
closely allied to tumor formation than inflammation; and it is very 
difficult to draw a sharp line between some forms of adenoma and 
sarcoma of the mucous membrane on the one hand, or chronic inflam- 



DISEASES OF THE REPRODUCTIVE ORGANS 



819 



mations on the other, in attempting which, one should remember that 
the glandular layer lies immediately upon the muscle, so that acini as 
deep as the muscle-bundles do not necessarily indicate malignancy. 

There is a tendency to remove the hyperplastic and hypertrophic 
changes of the glands from the category of endometritis and to place 
them among the permanent functional hypertrophies. During men- 
struation such a metamorphosis takes place normally and if it persist, 
definite enlargement of the glands remains. Since there are usually 
combined interstitial changes, chronic inflammatory lesions accom- 
pany this hypertrophy in the vast majority of cases. The mucous 
membrane may in the advanced stages be considerably swollen and pro- 
ject in a polypoid form (Fig. 406). Later, atrophy may take the place 



of hypertrophy, and in some instances the lining epithelial cells lose their 
cilia and change their character from the typical columnar cells to a 
distinct squamous type. The small glands of the membrane may be 
obstructed at their mouths and cystic distention may result. This is 
particularly conspicuous in the case of the Nabothian glands of the 
cervix, and retention cysts of these glands may reach the size of a pea or a 
small cherry. Occasionally, erosions or slight ulcerations are met with 
in cases of chronic endometritis. 

Chronic endometritis of the cervix is frequently secondary to in- 
flammations of the vagina, and may be due to gonorrheal infection or 
other causes. The mucous membrane of the cervical canal is greatly 
thickened, and may project from the os uteri (ectropium). Retention 
cysts of the Nabothian glands are sometimes a conspicuous feature, 
and cystic mucous polyps are not unusual. 

The tears and erosions incident to repeated pregnancies, especially 
if any be mechanically delivered, combined with hyperemia from 
uterine malpositions, favor chronic endo cervicitis. 

Chronic endometritis may lead to chronic metritis, or by extension 
may occasion tubal disease. Clinically, it is characterized by more 
or less constant mucopurulent discharge. 




Fig. 406. — Polypoid endometritis (Penrose). 



820 



A TEXT-BOOK OF PATHOLOGY 




Erosions of the uterus are especially frequent in the cervix; they 
result from endometritis. The mucosa within the cervical canal under- 
goes hyperplastic changes and projects from the os uteri in a polypoid 
form. Between the papillomatous projections cystic formations may 
develop, and these may rupture, leaving exposed ulcerations. Granu- 
lation tissue is developed and sometimes becomes exuberant in character. 
The term " erosion" is also applied to areas in which the normal squa- 
mous epithelium of the cervix has become converted into cylindrical, or in 
which the cylindrical epithelium of the body of the uterus has extended 

downward to the cervix. Other 
erosions are due to lacerations of 
the cervix (Fig. 407), and oc- 
casionally congenital erosion has 
been observed. 

Phagedenic ulceration of the 
cervix has been described as an 
independent disease. Some of the 
cases are undoubtedly instances of 
ulcerating carcinoma; in other 
cases ulcerations in this situation 
have been met with in which 
microscopical examination showed 
no evidence of carcinomatous tissue. 
Acute metritis is rarely met 

Fig, 407.— Left lateral laceration of the with except during the puerperium, 
cervix, with erosion (Penrose). but may be the result of acute 

endometritis. The wall of the 
uterus becomes thickened, soft, and edematous. Occasionally purulent 
infiltration is observed. 

Chronic metritis frequently occurs in the puerperium as a result 
of retarded involution of the uterus. It may be occasioned by chronic 
congestion of the uterus, or may be secondary to chronic endometritis. 
The uterine wall is infiltrated with round cells, and the connective 
tissues undergo active hyperplasia, which in the later stages leads to 
great thickening and induration. Coincidently, there is usually some 
hypertrophy of the muscular elements themselves. It is by no means 
certain that all of the cases grouped under this term are inflammatory 
in nature. Some are certainly more closely allied with diffuse tumor 
formation. The mucous membrane is usually thickened, and becomes 
secondarily involved if it was not primarily diseased. The peritoneal 
covering may be similarly affected, and chronic perimetritis with adhe- 
sions of the uterus results. 

INFECTIOUS DISEASES 

Puerperal Infections. — This term may be applied to various forms 
of infection occurring during the puerperium, but in the majority of 
instances the streptococcus is the specific organism. 

Etiology. — Two important factors are concerned: (a) Injuries to 
the surface of the uterus, vagina, or vulva; and (b) some form of infec- 
tion. The more or less denuded surface of the uterus offers a ready 



DISEASES OF THE REPRODUCTIVE ORGANS 



821 



entrance to micro-organisms, as well as an absorptive surface for soluble 
poisons produced by micro-organismal decomposition within the uterus; 
and infection may take place without any further injury than that occa- 
sioned by the normal processes of labor. In most instances, however, 
there is actual injury either of the surface of the uterus, cervix, vagina, 
or vulva, and the micro-organisms or poisons are admitted through 
these wounds. There may be primarily, however, more than a simple 
injury of the mucous surface. In consequence of prolonged pressure 
necrotic lesions terminating in gangrene may first be established, and 
from this secondary infections may take place. In cases in which infec- 
tion occurs without injury to the walls, as well as in cases in which 
injury has been sustained, the pathogenic organisms may first find 
a lodgment and multiply within blood-clots or retained secundines 
within the uterus; and the organisms or their toxic products are sec- 
ondarily admitted to the uterine tissues. 

Puerperal infection is probably in most cases the result of the en- 
trance of micro-organisms from without, and may be traced to want 
of cleanliness on the part of the accoucheur or the surroundings. Some- 
times widespread epidemics have been caused by the carelessness of a 
single obstetrician, whose hands perhaps had become infected from oper- 
ating upon or examining cases of erysipelas, general pyemia, or the like. 

Among the micro-organisms, as has already been stated, the Strepto- 
coccus pyogenes is most important. Staphylococci of various sorts, 
bacilli resembling the Bacillus coli communis, the bacillus of tetanus, 
gonococci, and other organisms occasionally infect the puerperal uterus, 
but in these instances the pathological conditions are different from 
those met with in ordinary puerperal infection, which may be con- 
sidered as practically always a streptococcic infection. 

Pathological Anatomy. — In most instances there is primarily a 
lesion upon the mucous surface of either the uterus, the vagina, or the 
vulva. The nature and extent of this depend upon the amount of in- 
jury occasioned during labor. In some instances the lesion is trivial 
in extent, and remains so, though widespread infection results from it. 
In most cases, however, there is a rapidly spreading inflammation of 
the endometrium or mucosa of the vagina, and pseudomembranous de- 
posits are very frequently met with upon the surface. Necrotic and 
gangrenous changes in the mucous membrane are most pronounced in 
cases in which prolonged pressure has been exerted by the head in its 
descent or by instruments and at such areas ragged spreading ulcers 
may form or the surface may be covered by a false membrane that in 
time extends over the whole uterine interior. 

The extension of the infection may occur in two ways, either through 
the blood-vessels or through the lymphatic channels; and the local and 
general lesions vary correspondingly. 

In cases in which the infection spreads along the blood-vessels there 
may be primarily septic softening of the thrombi within the uterus 
and purulent phlebitis of the venous channels at the placental site. 
Thrombosis extends from this situation through the veins to the various 
plexuses in the vicinity, and infected emboli are carried through the 
circulation to distant organs, such as the lungs, the kidneys, and the 



822 



A TEXT-BOOK OF PATHOLOGY 



spleen. Metastatic abscesses and inflammatory swelling of the affected 
organs result. The kidneys in particular are often the seat of numerous 
punctate or miliary abscesses. 

In the cases in which extension occurs along the lymphatic channels 
the uterus is enlarged, soft, and often pultaceous. Streaks or lines of 
light color may be observed running from the mucous surface toward 
the periphery. These represent the lymphatic vessels filled with puru- 
lent exudate. The walls of the lymphatics may be penetrated, and peri- 
lymphangitic abscesses are thus occasioned. When the process has 
extended to the lymphatics in the outer layers of the uterus, phlegmonous 
inflammation of the subperitoneal tissues (parametritis) results, and 
finally the peritoneum itself may be involved. 

The spleen is enlarged, though less decidedly than in the form in 
which infection occurs through the blood-vessels. 

Extension along the mucous membrane itself may lead to asso- 
ciated disease of the tubes; more frequently the tubes are invaded at 
their abdominal end after peritonitis has developed. 

Puerperal sepsis is peculiarly virulent and rapid in its course, 
and may occasion widespread changes in all of the tissues of the 
body. Less fulminating infection emanating from the uterus after 
delivery may take the form of a purulent endometritis which slowly 
spreads to the tube and ovary or to the parametrium (q. v.) upon which, 
last may succeed peritonitis and thrombophlebitis. Localized septic 
metritis also occurs, which may become later a septicemia or it may heal 
leaving a weak spot in the musculature of the organ. Sapremia is the 
absorption of decomposed secundines without septicopyemia or necrot- 
izing lesions in the uterine wall. 



Fig. 408. — Diffuse tuberculosis (ulcerative and caseous) of the endometrium (Kaufmann). 




Tuberculosis of the uterus is most frequently met with in the 
mucous membrane of the uterine body, and is usually secondary to 
disease of the tubes. Direct infection may possibly occur through 



DISEASES OF THE REPRODUCTIVE ORGANS 



823 



coitus, but is certainly rare. The disease occurs in the form of a nodular 
or diffuse infiltration with a tendency to rapid ulceration or caseous 
necrosis involving the mucous membrane and to some extent the sub- 
mucosa. The entire cavity of the uterus may be covered with caseous 
and necrotic deposits (Fig. 408). In the later stages the process may 
extend deeply, even involving the muscular layer of the organ. The 
cervix is rarely attacked. Sometimes miliary tubercles are found in the 
uterine mucosa without marked degeneration (Fig. 409). 




V 



Fig. 409. — Miliary tuberculosis of the endometrium and glandular endometritis (Beyea). 

Syphilis of the cervix uteri may occur in the form of a chancre, a 
condyloma, or as tertiary infiltration, but active lesions of the body are 
rare, although it is infected as indicated by syphilitic placentas and 
fetuses. 

ATROPHY AND DEGENERATION 

Puerperal Atrophy. — 'The uterus suffers a most remarkable atrophy 
following labor. This proceeds very rapidly at first, and then more 
slowly; and under favorable conditions the organ resumes its previous 
condition in the course of a few months. The muscular fibers decrease 
progressively, from their previous hypertrophied conditi on in which 
they frequently attain a length and diameter three times the normal, 
until, at the end of involution, the usual size and appearances are at- 
tained. Many muscle-fibers undoubtedly are destroyed. The process 
of involution is really one of fatty degeneration. 

Senile Atrophy. — The uterus undergoes progressive atrophy at and 
after the period of the menopause, and finally becomes greatly reduced 
in size. The substance of the organ may undergo a progressive sclerosis, 
or in other instances becomes softer than normal. Catarrhal endo- 
metritis is often associated, and the columnar cells are sometimes con- 
verted into squamous epithelium. 



824 



A TEXT-BOOK OF PATHOLOGY 



Fatty degeneration, independent of that which occurs during 
puerperal involution, is a rare condition, but may occur in the course 
of certain infectious diseases, such as typhoid fever, or may result from 
the action of the parenchyma poisons. 

Amyloid infiltration is rare and unimportant. 

HYPERTROPHY AND HYPERPLASIA 

Hypertrophy of the entire uterus may occur in association with 
inflammation or metritis, or may result from chronic congestion of the 
organ. The enlargement in cases usually designated as hypertrophied 
is, for the most part, due to new formed connective tissue. True hyper- 
trophy occurs as a physiological process during pregnancy. In this 
variety the muscle-fibers increase enormously in size, and doubtless 
also multiply their number. The blood-vessels and connective tissues 
undergo corresponding hypertrophy. 

Hypertrophy of the cervix uteri is occasionally met with inde- 
pendent of hypertrophy of the uterus as a whole. It may be caused by 
chronic irritations of the cervix, as in cervical endometritis, or may result 
from obscure causes. Frequently it is met with in prolapse of the uterus, 
and sometimes its elongation simulates prolapse. 

Hyperplasia of the mucous membrane of the uterus has been re- 
ferred to in the discussion of chronic endometritis. In some instances 
that are designated as endometritis the pathological process seems to 
be rather of a purely hyperplastic character, and more closely allied to 
tumor formation than to ordinary inflammation. In these cases the 
mucous membrane in all parts of the uterus may be greatly thickened, 
and may suffer more or less papillomatous transformation. Sometimes 
limited portions are affected, and polypoid formations result. 

Polypi of the uterus may be of various sorts. Very commonly they 
present themselves as simple mucous polypi, due to projection of parts 
of the mucous membrane; in other cases secondary changes, such as 
cavernous dilatation of the blood-vessels or cystic transformation of 
the small glands contained in the polyp, occasion marked variations from 
the original appearances. Myofibromata, sarcomata, and other forms of 
tumors originating in the mucous membrane or just beneath it may 
assume a polypoid appearance. 

TUMORS 

Leiomyoma; Myofibroma; Fibroid. — The tumors of the uterus 
designated by these terms are in nearly all cases composed of smooth 
muscle-fibers and fibrous tissue, and from the pathological standpoint 
the term " myofibroma " is, therefore, most applicable. There are many 
grades of combination in these tumors. Beginning with the soft red, 
illy outlined tumor composed almost entirely of muscle-cells, they pass 
into forms of paling color and increasing consistency to the almost stony 
hard fibroid mass, which shows either no muscle-cells or only the fattily 
degenerated remains thereof. They present themselves in the form of 
rounded and usually well-circumscribed masses, from the size of a grape 
seed to that of tumors weighing 40 or 50 pounds. They are generally 
multiple, and on section have the appearance of concentric or irregular 



DISEASES OF THE REPRODUCTIVE ORGANS 



825 



lamellae. Microscopically, the tumors are composed of smooth muscle- 
fibers and of fibrous tissue arranged in bundles or layers running in various 
directions. The muscle-fibers are frequently found arranged concentric- 
ally about small blood-vessels, and in some instances the vessels are telan- 
giectatic. They occur chiefly in late menstrual life and occasionally 
disappear after the menopause. During pregnancy, because of the in- 
creased blood-supply, growth is active while, when nutrition is reduced 
by the contraction of vessels during involution, recession is often observed ; 
this reasoning may also explain recession after the climacteric. 

Secondary changes are very common, the most frequent being cal- 
cification. This may begin either in the center or at the periphery, but 
more commonly it is diffuse. Edema of the tumor may cause it to 
become quite soft, and cystic transformations due to degenerative or 




Fig. 410. — Interstitial fibroid tumor of the uterus: a small submucous fibroid appears in 

the uterine cavity (Penrose). 

autolytic softening or to distention of the lymphatic spaces are sometimes 
observed. Infections may occur by contiguity or via the blood stream. 
Sarcomatous metamorphosis sometimes occurs but the diagnosis is 
extremely difficult. When it is a true malignant change, there are numer- 
ous mitoses and giant cells, while the mass as a whole fails to keep its 
sharp outline, invasive spread occurring. Thromboses and angiomatous 
formations give rise to what is known as red degeneration. Myxoid 
changes appear at times. Necrosis, focal or total, occurs when the circu- 
lation is obstructed. 

Several varieties have been distinguished, according to the seat of 
the tumors. In some instances they are embedded in the wall of the 
uterus, when the term interstitial or mural fibroids is applied (Fig. 410). 
In other cases they arise in the uterine walls just beneath the mucous 
membrane, when they are called submucous fibroids. These may gradu- 
ally project into the cavity of the uterus as fibroid polypi; in these cases 
hypertrophy of the organ similar to that of pregnancy is apt to occur and 
the mucosa over the tumor is thinned out. In the third group of cases the 



DISEASES OF THE REPRODUCTIVE ORGANS 



827 



tumors have a subperitoneal location, and may project from the outer 
surface of the uterus as knobbed masses (Fig. 411), which may become 
pedunculated. In rare instances they extend between the layers of the 
broad ligament. Fibroid tumors are benign in a pathological sense, 
but occasion serious disturbances either by pressure, by obstruction to 
labor, or by the metrorrhagia and endometritis to which they frequently 
give rise. Subperitoneal fibroids may become free bodies in the perito- 
neal cavity, and the submucous form is sometimes discharged from the 




Fig. 413. — Grape sarcoma, or sarcoma botryoides. The vagina is seen crowded with grape- 
like masses of the growth. (Graves: copied from a drawing in Kiistner's Handbuch.) 

uterus after a spurious labor. The so-called adenomyoma and adeno- 
fibroma are tumors including some epithelial structures as nests or 
cystic glands. They are due most likely to a downgrowth of the super- 
ficial epithelial structures, but it has been maintained that they are 
due to remnants of Wolffian body. Some view them as results of 
inflammation and have applied the name " adenomyositis." They do 
not grow like simple adenomata nor behave like malignant adenomata 
(Fig. 412). They grow in a diffuse irregular manner that permits of no 
definite margination, most often at the posterolateral aspect of the fundus. 

Sarcoma of the uterus may arise from the muscular layer or from 
the endometrium. That arising from the myometrium is usually asso- 
ciated with myoma and fibroma. In some cases the sarcomatous ele- 



828 



A TEXT-BOOK OF PATHOLOGY 



ments of the tumor are developed in a pre-existing myofibroma. In 
other cases the sarcoma and fibroma are coincidently formed. These 
tumors differ from typical fibroids in being more rapid in growth, less 
well circumscribed, softer, and more homogeneous in appearance. Some- 
times they are situated just beneath the endometrium, and become con- 
verted into sarcomatous polypi. 

Sarcoma of the endometrium may occur in a circumscribed or papil- 
lomatous and in a diffuse form, the latter involving the entire mucous mem- 
brane of the organ. The papillomatous variety is soft and villous and 
highly vascular. In some cases the structure is that of angiosarcoma. 
In the diffuse form the entire cavity of the uterus may be filled with soft 
villous projections from the mucous membrane. 

A special form of sarcoma has been described as occurring in the 
vaginal portion and cervix. In this the tumor has a grape-like structure, 
and, microscopically, consists of myxomatous tissue with areas of sarco- 
matous character. It occurs in young persons, even in childhood. 

Syncytioma Malignum. — (See pp. 250 and 859.) 

Adenoma may occur in the form of polypoid outgrowths from the 
mucous membrane, or as a diffuse process not readily distinguishable 
from that commonly designated as endometritis glandularis. Both of 
these forms are benign. 




Fig. 414. — Malignant adenoma. The section is taken from the deeper parts of the tumor, 
and shows the invasion of the myometrium. 



Malignant adenoma usually arises from the corpus uteri, and pre- 
sents itself as a soft, irregular elevation of the mucous membrane in a 
localized area, or diffusely involving a large part of the endometrium. It 
tends to spread through the walls of the uterus, invading the myome- 
trium (Fig. 414), and finally penetrating to the peritoneal covering, where 
secondary nodules may develop. Histologically, it is characterized by 
the production of atypical, branched, intercommunicating, or cj'st-form- 
ing gland-acini with comparatively little stroma, the latter being of 
soft fibrous character. The tumor is malignant in its tendency to in- 
vade the wall of the uterus and neighboring structures, and it may 



DISEASES OF THE REPRODUCTIVE ORGANS 



829 




Fig. 416. — Diffuse cancer of the endometrium (Penrose). 



830 



A TEXT-BOOK OF PATHOLOGY 



become converted into actual carcinoma in the later stages. In such 
instances the acini in places show a heaping of epithelial cells and a 
tendency to destruction of the basement-membrane, with proliferation 
of the cells in the stroma. 

Carcinoma is the most frequent of the malignant diseases of the 
uterus, and usually invades the cervical portion; more rarely it arises 
from the corpus uteri. Carcinomata starting on the vaginal surface of 
the cervix are squamous-celled epitheliomata ; those originating in the 
cervical canal and in the corpus uteri are tubular or glandular carcino- 
mata. 




Fig. 417. — Everting cancer of the cervix (Graves) 



Carcinoma of the portio vaginalis usually begins from the inner surface 
of one of the hps of the os uteri, and causes a firm infiltration of the af- 
fected portion, the disease penetrating into the submucosa and muscu- 
laris. Subsequently, ulceration takes place, and the diseased area becomes 
converted into an elevated and irregularly ulcerated surface. Extension 
may take place to the vaginal walls and to the tissues surrounding the 
cervix uteri (Fig. 419). Ulceration may establish communications be- 
tween the vagina and bladder or rectum. Extension upward into the 
supravaginal portions of the cervix and to the corpus uteri may occur 
through the lymphatic channels, or by direct invasion. Secondary in- 
volvement of the lymphatic glands of the iliac, lumbar, and inguinal 
groups is frequent. 



DISEASES OF THE REPRODUCTIVE ORGANS 



831 



Instead of the usual indurated and ulcerating form, cervical epithe- 
lioma may present itself as a cauliflower growth— that is, as a destructive 
or malignant papilloma. In such cases it is likely that the growth often 
begins as a papilloma, causing irregular elevations, and that the penetra- 
tion into the tissue at the base of the. growth is a secondary development. 
In the later stages this form, like the preceding, undergoes ulceration. 
Extension to the uterine wall and to the parametrium occur much later 
than from the endocervical form, while direct extension to the bladder 
is seen earlier. Both varieties, but particularly the latter, frequently 
cause uterine hemorrhages. 




Fig. 418. — Inverting cancer of the cervix (Graves). 



Carcinoma of the corpus uteri and of the cervical canal develops 
from the tubular and racemose glands of the mucous membrane. It 
may begin as an adenomatous growth, subsequently becoming trans- 
formed into carcinoma. Macroscopically, the growth presents itself 
as a villous or papillomatous thickening of the mucosa, either localized 
or diffuse (Figs. 416 and 419), the surface of which is apt to be ulcerated 
and even bleeding, while the cut surface shows a glistening grayish in- 
filtrating mass against the dull brownish red of the uterine wall. In 
the later stages considerable involvement of the wall of the uterus occurs, 
and even perforation may take place. Microscopically, the usual ap- 
pearances of simple, medullary, scirrhus, or glandular cancer or of adeno- 
carcinoma are discovered (Fig. 420). Metastasis occurs chiefly to the 
liver, lungs, kidney and ovary. 



832 



A TEXT-BOOK OF PATHOLOGY 



Squamous epithelioma is met with in rare instances in the corpus 
uteri, especially in women of advanced years. The explanation of this 
growth is that it arises from epithelium that has undergone a change from 
the customary columnar to the squamous form, in consequence of chronic 
endometritis. 




Fig. 419. — Cancer of the body of the uterus: a large, single cancerous nodule in the anterior 
wall has been divided (Penrose). 




Fig. 420. — Medullary cancer of the uterus with necrosis in the center of nests. 

Because of the ulceration and secondary infection to which carcinoma, 
especially of the lower segment of the uterus, is especially liable, it is 
frequently the case that secondary infection arises from them. More- 
over by their mechanical presence or the secondary infection by it in 
the birth canal or urinary organs, the passage of excretions is hampered. 
Thus parametritis, hydronephrosis, cystitis, pyelonephritis may occur. 



DISEASES OF THE REPRODUCTIVE ORGANS 



833 



Cysts. — Small cysts of the wall of the uterus may be associated 
with various forms of tumors, such as myo fibromata ; and a form of 
adenocystoma, probably originating from remnants of the Wolffian 
duct, has been described. Dermoid cysts have been occasionally ob- 
served. 

PARASITES 

Echinococcus cysts are sometimes met with, and a few cases of sup- 
posed Cysticercus cellulosm have been described, though the nature of the 
formations was uncertain. 

The Ovaries 

Development and Anatomical Considerations.— The ovary and 
testis are developed from a primary indifferent sexual gland, which is 
indistinguishable in the two sexes. This indifferent gland is formed on 
the ventromesial surface of the Wolffian body by a localized thickening 
of the mesothelial elements. The ovarian stroma is subsequently formed 
by ingrowths of the surrounding mesoderm. The ovary consists of a 
stroma of peculiar spindle-shaped connective-tissue cells. In the central 
or medullary portion the tissue is highly vascular; the peripheral or 
cortical part contains abundant Graafian follicles in which the ova are 
developed. These follicles are formed from primary tubular indentations 
of the cuboidal or columnar epithelium that covers the organ, cells that 
are physiologically similar to the epithelium of the tubes and ovaries. 
These indentations are the tubes of Pfliiger. After full development of 
the ovary they are wanting, the greater part, by constriction of the deeper 
portions, having formed primordial follicles. The paroophoron, a vesti- 
gial structure, is the part of the ovary at the hilum. It consists of con- 
nective tissue and blood-vessels with a number of parallel tubes which are 
remnants of the Wolffian body. The same tubules surrounded by con- 
nective tissue extend outward between the layers of the broad ligament, 
constituting the parovarium. Sometimes pa rt of the Wolffian duct remains 
patulous and constitutes the duct of Gartner. This is the homologue 
of the vas deferens. 

CONGENITAL ABNORMALITIES 

Occasional absence of one or both ovaries has been discovered with 
other developmental defects, or independently. Hypoplasia occurs in 
chlorosis, and occasionally in association with other conditions. Some- 
times supernumerary ovaries have been found. The additional ovaries 
may be formed by division or by separation from one of the normal 
glands. 

CHANGES IN POSITION 

More or less extensive dislocations of the ovaries may occur, the 
most notable being that in which one of these organs descends into a 
hernial sac, occupying either the inguinal or crural canal. Dislocations 
resulting from pressure, adhesions, and the like are frequent. 

53 



834 



A TEXT-BOOK OF PATHOLOGY 



CIRCULATORY DISTURBANCES 

Active hyperemia, or congestion, may be either a physiological or 
pathological condition. The former occurs during the menstrual period, 
the latter in association with inflammation of the neighboring structures 
or in the earlier periods of inflammation of the ovaries themselves. 

Passive congestion is met with in chronic cardiac diseases, and as a 
result of local obstructions to the circulation by tumors, inflammatory 
adhesions, torsion of the tube, and uterine displacements. 

Hemorrhage. — Small hemorrhages into the ovarian tissue are very 
frequent. Their occurrence is usually sufficiently accounted for when 
the functional activity of the organ is considered. At each periodical 
ovulation a small follicle ruptures, to discharge the contents containing 
the ovum. Generally there is a slight extravasation of blood at such 
times, which is subsequently absorbed. At the same time that the ex- 
travasation and absorption are taking place the inner lining of the follicle 
proliferates somewhat, and the cells then undergo fatty degeneration. 
The whole process gives rise to a yellowish nodular formation, termed the 
corpus luteum, Subsequently this is removed by absorption of the blood 
and by degeneration and absorption of the proliferated cells of the lining 
membrane, and a small scar alone remains. The latter, especially when 
more than usually fibrous, is known as the corpus fibrosum. This is com- 
monly a little pigmented, in consequence of the pre-existing extravasation 
of blood. The corpus luteum, which is developed from a follicle formed 
at the time of impregnation (corpus luteum of pregnancy), differs some- 
what in character. The epithelial proliferation is much more active, and 
the wall of the follicle is intensely congested. Rapid involution does not 
take place, the follicle often persisting for considerable periods after the 
termination of pregnancy, and acting, according to the present view, 
as a glandular organ with an internal secretion having an inhibitory 
effect upon further ovulation, but inciting growth of decidua and, pos- 
sibly, activity in the mammae. 

Exceptionally, considerable hemorrhages may take place into the 
follicles, and small hemorrhagic cysts or spaces containing blood-stained 
liquid may be formed. Massive hemorrhages, suggesting the rupture of 
an ectopic pregnancy in symptomatology and gross anatomical appear- 
ance but without microscopical evidences of impregnation, have been 
known to lead to a fatal outcome unless treated surgically. The cause 
of such an occurrence is not known but the point of bleeding is usually 
a Graafian follicle. 

INFLAMMATION 

Inflammation of the ovaries, or oophoritis, is generally a second- 
ary condition resulting from an extension of inflammation from the neigh- 
boring reflections of the peritoneum, or from extension of infective proc- 
esses along the Fallopian tube. Inflammation of the ovary as a whole 
is quite rare, the lesions covered here being especially perioophoritis. 
The commonest causes are puerperal and gonococcal infections. The 
extension from the neighboring peritoneum, as well as from the uterus, 
may be direct — that is, along the planes of tissue or through the lymphatic 
or vascular channels. Acute oophoritis is not infrequent in various forms 



DISEASES OF THE KEPEODUCTIVE ORGANS 



835 



of general infection, such as typhoid fever, pneumonia, influenza, etc. 
Primary oophoritis is probably very rare. 

The ovary becomes enlarged, and in the earlier stages is more or less 
congested. Later, the organ becomes yellowish, either uniformly or in 
scattered areas, its surface in severe cases not infrequently being covered 
with plastic exudate. Finally, the process may terminate in necrosis or 
abscess formation. Since such purulent collections either extend or 
perforate into the tube, tubo-ovarian abscesses arise. Such ovarian ab- 
scesses may reach a considerable size, and break into any of the hollow 
viscera near by or into the peritoneal cavity. In more favorable cases 
there are only small collections of pus, and these may subsequently be- 
come inspissated. The most satisfactory of all terminations is in com- 
plete resolution or in induration (chronic oophoritis). The ovary in 
chronic oophoritis shows the changes most upon or near the surface, a 
condition which leads to fibrous adhesions to the peritoneum, while the 
interior usually undergoes atrophy, which, since there are definite thicken- 
ings or degenerations of the smaller blood-vessels, seems to have a func- 
tional basis. This is borne out by the facts that complete Graafian fol- 
licles cannot rupture since the surface of the organ is indurated, and that 
there is a disappearance of primary follicles and some replacement fibrosis. 
This leads to the atrophic cystic ovary (see below). Primary fibrotic 
atrophy without superficial inflammation occurs in senility and sometimes 
as the result of infectious states, intoxications and anemia. The organ 
in chronic inflammation, except where cysts are numerous or large, is 
small, white, and quite firm. 

Localized inflammations may sometimes occur about the follicles. 
These may terminate in follicular abscesses, which either discharge and 
lead to scar formation or become inspissated. 

INFECTIOUS DISEASES 

Tuberculosis. — Among the infectious diseases, tuberculosis alone is 
of importance. It may arise as a primary disease of the ovaries, but 
much more frequently is secondary to inflammation of the tubes or 
other parts of the genital tract. It may give rise to the formation of 
small or large cheesy masses, showing a tendency to softening with 
formation of tuberculous abscesses. The ovaries may occasionally be 
the seat of miliary tuberculosis. 

TUMORS 

The ovaries are frequent seats of tumors, both benign and malignant. 
By far the largest proportion are cystic. 

Connective=tissue Tumors. — Fibromata may occur as small nodu- 
lar growths, either single or multiple. In some cases the tumors are of 
considerable size. Combinations of fibroma with leiomyoma may also 
be met with; these myofibromata resemble those of the uterus. Occa- 
sionally fibrosarcoma is encountered. Chondroma is a rare form of be- 
nign tumor, usually teratomatous in nature. 

Sarcoma may occur in the form of spindle-celled sarcoma, fibrosar- 
coma, or, more rarely, as round-cell sarcoma, but all forms are noteworthy 
for the varyin g size of the cells in the same tumor. It appears as a rounded 



836 



A TEXT-BOOK OF PATHOLOGY 



tumor with more or less pronounced encapsulation. Degenerations, 
such as myxomatous, are not infrequent, and cystic change may be 
occasioned by dilatation of the follicles. In some cases proliferations 
of the walls of the follicles constitute an important part of the growth. 
To such cases the name a adenosarcoma " may be applied. 

The ovary is a favorite seat of mixed tumors, most of which are 
teratomatous and fall into two classes, solid and cystic, of which the 
latter are more common and important. All sorts of combinations among 
the benign and malignant growths, or mixtures of these, have been seen. 
The benign tumors, especially if cystic, are prone to undergo malignant 
change. 

Cystic Tumors. — Of the cystic conditions of the ovary we must 
distinguish the simple follicular cysts, and the more important myxoid 
or colloid cystomata and dermoid cysts. Of the cystomata, there are 
two varieties — the papillary and the glandular. 

Follicular cysts are developed by distention of the Graafian follicles 
with dropsical liquid. The ovary may be considerably enlarged by 
cystic cavities, lined with epithelium, and containing clear watery liquid 
or, occasionally, blood-tinged contents. Cysts of this character are very 
common in cases of induration of the ovary following oophoritis. One 
form of this follicular cyst formation is so extensive that it seems as if all 
the potential Graafian follicles had attempted to ripen and had filled 
up with clear fluid. This is the " cystic degeneration of the ovary," 
and forms a large cystic mass with little organ tissue remaining. 

Colloid or myxoid cystomata present themselves as tumors of small 
or large size, having a tendency to a multilocular cystic character. 
The cavities are filled with a more or less gelatinous or mucoid liquid. 
Sometimes hemorrhage takes place, and the contents are correspondingly 
altered. Two sub varieties may be distinguished: the glandular and the 
papillary. 

Glandular cystomata are distinguished by the constant prolifera- 
tion of the epithelial elements in the form of acini. This occasions a 
multilocular character, new cysts springing from the walls of the original 
cavity or appearing within the substance of the primary tumor. The 
terms adenocystoma and cysto-ddenoma are appropriate. The tumor may 
present itself as a large, single, rounded, unilateral or bilateral cyst with 
insignificant projections of small cysts upon the inner lining; while in 
other cases there is found on section a uniform multilocular character. 
Microscopically, the characteristic feature of tnese tumors is the forma- 
tion of regular gland acini, showing a single layer of epithelial cells, or 
at most a few layers resting upon a basement-membrane, the lining 
showing a tendency to sprout from or sink into the wall, in either case 
to form new cysts. The stroma of the tumor is composed of fibrous 
connective tissue, with some unstriped muscle-fibers. The contents of 
the cysts have the mucoid or colloid character referred to, and chemically 
a substance is discovered that is absent from simple follicular cysts of 
the ovary and is less abundant in papillary cystomata. This substance 
is termed " pseudomucin " or " paralbumin," and is somewhat related to 
mucin. Occasionally, when the cysts are old, the contents may be quite 
watery. 



DISEASES OF THE REPRODUCTIVE ORGANS 



837 



Cystomata soon destroy the ovary, the unaffected ovarian tissue 
being spread out within the wall of the cyst. The tumor is attached 
in the pelvis by a pedicle consisting of the broad ligament and Fallopian 
tube, and often forms secondary inflammatory adhesions to adjacent 
parts. * 

Glandular cystomata arise either from embryonal rests (Pfliiger's 
tubes) or from ingrowths of the surface epithelium of the organ. It is 
generally considered unlikely that they arise from Graafian follicles. 

Papillary Cystomata.— Papillary cysts occur in two forms, the one 
closely resembling glandular cystoma in its general appearance, the 
other presenting itself as a papillomatous condition of the surface of the 
ovary (Fig. 421). In the former, or papillary myxoid cystomata, large 




Fig. 421. — Papillary adenoma of ovary. 

cystic tumors are developed. On section through these there is found a 
papillomatous or cystic proliferation of the lining membrane, but the 
tendency to the formation of secondary cysts is much less pronounced 
than in the glandular varieties, and the fibrous stroma is less abundant. 
The secondary cysts in this variety may be formed by fusion of the free 
ends of proliferating papillae, or by myxomatous degenerations within 
the stroma of the papillae. The liquid of the cysts resembles that of the 
glandular form, but contains less pseudomucin, and is more frequently 
hemorrhagic. On microscopical examination it is found that the inner 
lining of the cyst and the papillary projections consist of stratified ciliated 
epithelium. Calcareous bodies arranged in a concentric fashion (psam- 
moma bodies) are frequently met with in the stroma, as well as in the 
epithelium. The same calcareous bodies are occasionally found in 
glandular cystomata. 



838 



A TEXT-BOOK OF PATHOLOGY 




J 



Fig. 422. — Double papillomatous cyst of the ovary: the right cyst has ruptured and is 
turned inside out, showing a mass of papillomata; papillomata have penetrated the wall 
of the cyst; the peritoneum has been infected, and a papillomatous growth appears on 
the fundus uteri (Penrose) . 




Fig. 423. — Papillary cystadenoma of the ovary (Graves). 



DISEASES OF THE REPRODUCTIVE ORGANS 



839 



The papillomatous ovarian tumors differ from the glandular in 
being almost invariably bilateral (Fig. 422). Their origin has not as 
yet been certainly determined, but it is probable that they originate 
from the paroophoron, a vestigial remnant of the parovarium. Some 
have held that they may originate from the Graafian follicles or from in- 
growths of the surface epithelium. This is assuredly not a frequent 
origin. 

The surface papillomata of the ovary present themselves as irregu- 
lar masses of a cauliflower appearance. The papillary projections are 
covered with cylindrical epithelium, as in the cystic form. There is no 
essential difference in structure, and it is probable that in many instances 
the superficial forms result from a rupture of the cystic variety and the 
subsequent external proliferation. 

The papillomatous cystomata and the surface papillomata have a 
marked tendency to carcinomatous transformation, and tend to spread 
to the peritoneum, causing metastatic nodules in the vicinity or through- 
out the entire abdomen. 

Both these cysts, especially the former, give rise to the so-called 
" pseudomyxoma peritonei" when they rupture. The latter cyst is more 
malignant than the former, as it can infiltrate through the cyst wall 
and extend by continuity. Frank carcinomatous change is possible 
with metastases in distant organs. 

Dermoid cysts are frequently met with in the ovary. They may 
occur as small nodules or as very large tumors, and are usually uni- 
lateral. The larger ones substitute the ovarian tissue completely; less 
commonly they may be pedunculated, the ovary in part remaining in- 
tact. Combinations with glandular cystomata are not infrequent. 

The dermoid cyst is a smooth-walled sac, the inner surface present- 
ing somewhat irregular projections and having more or less pronounced 
characteristics of epidermal tissue. The cystic contents are a putty-like 
material of grayish color, containing long blonde hairs and teeth, and 
sometimes ill-developed bone. The grayish material consists of fatty 
detritus containing degenerated epithelial cells, and usually abundant 
cholesterin crystals. The wall of the dermoid cyst, though usually in 
the main composed of epidermal structure, may contain elements of the 
three blastodermic layers. The dermoid cyst may occur in childhood 
or even in fetal life, but usually does not present itself until adult years. 

Secondary changes not infrequently occur. Inflammatory condi- 
tions of the walls may occasion abscess. Sometimes the epithelium pro- 
liferates actively, and the dermoid, in part or as a whole, is converted 
into a carcinoma. 

Carcinoma of the ovary may be a primary growth derived in all 
probability from the surface epithelium or it may originate from a cys- 
toma or dermoid. Any variety may be cystic. Histologically medullary 
or glandular types are encountered. Krukenberg gave his name to a form 
characterized by the presence of a large amount of clear material desig- 
nated colloid, both between and within cells, in the latter case causing 
vacuolization and distortion of the nucleus; it is frequently bilateral. 
This appearance has also been seen in secondary cancers of this organ. 
Cancers of these organs are apt to be limited and not to spread actively. 



840 



A TEXT-BOOK OF PATHOLOGY 



Mention has already been made of the carcinomatous change in cyst- 
adenomata. When such metamorphosis occurs one finds distinct 
epithelial cell nests besides the proliferating and atypical gland cavities. 
The solid cancers of the ovary are usually of the medullary type, but 
connective tissue may be prominent. 

Secondary tumors of the ovary, usually carcinomatous, are not com- 
mon, yet when they occur frequently attain great size, out of proportion 
to what might be expected from the size of the original mass. They 
may be multiple. Metastasis is commonest from the mammae, stomach, 
and rectum, usually by the hematogenic route or through the peritoneum. 

CYSTS OF THE PAROVARIUM 

Cysts of the parovarium may be considered in this place on account 
of their clinical resemblance to ovarian cystomata (Fig. 424) . They are 




Fig. 424. — Parovarian cyst; elongation of tube; no distortion of ovary. 

distinguished, however, by their intraligamentous situation, by their 
almost invariably unilocular character, and usually by their clearer and 
more serous liquid contents. The ovary is usually uninjured. The 
inner lining consists of ciliated epithelium. 

CYSTS OF KOBELT 

These are thin-walled, pedunculated cysts about the size of a pea 
(Fig. 425). They are frequently met with, and are seated at the side 



DISEASES OF THE REPRODUCTIVE ORGANS 



841 



of the ovary. The wall is fibrous, the lining membrane composed of 
cubical epithelium, and the contents a clear serous liquid. The cyst 
results from distention of one of Kobelt's tubes in the parovarium. 




Fig. 425. — Fallopian tube, ovary, and parovarium: a, Hydatid of Morgagni; 6, cyst of 
Kobelt's tube; c, Gartner's duct (Penrose). 

The Fallopian Tubes 

Development and Anatomy. — The tubes are formed from the 
upper ends of Muller's ducts. The lower ends of the ducts fuse to form 
the uterus and vagina. Each tube is covered by a peritoneal coat, and 
its walls consist mainly of longitudinal and circular muscle-fibers. The 
mucosa is thrown into well-marked longitudinal plications, which at 
the uterine end are further complicated by secondary elevations. The 
epithelial lining consists of columnar ciliated cells. 

CONGENITAL ABNORMALITIES 

The tubes may be absent or may be defective. Congenital atresia 
is occasionally observed. The tubes may be unusual in length and 
may communicate with the uterus in abnormal situations. 

CHANGES OF POSITION 

In dislocations of the ovaries the tubes are correspondingly dislocated. 
Independent of displacements of the ovary, the tubes may be distorted 
or pulled out of their usual position by inflammatory adhesions, and may 
thus be bent at sharp angles or bound down in various malpositions. 

STENOSIS 

Congenital stenosis of the tubes, or complete closure of the lumen, 
may affect the entire length of the tube or a limited portion, principally 
near the middle. Acquired stenosis may result from pre-existing disease 
of the tube itself, or from adhesions secondary to localized peritonitis. 
The most frequent situation in these instances is the abdominal or fim- 
briated end. A narrowing of the lumen of the tube may be occasioned 
by angulation or by dislocations. 



842 



A TEXT-BOOK OF PATHOLOGY 



DILATATION 

Dilatation on the proximal side of obstructions or stenosis is fre- 
quent. The dilatation is more marked when inflammatory conditions 
of the mucous membrane are present. The abdominal end of the tube 
may enlarge so as to form a cyst of considerable size, filled with serous 
or seromucous liquid, when the middle portion is stenotic. When the 
lower end is obstructed the entire tube becomes dilated, and it frequently 
shows a tortuous and irregularly pouched condition, due to its attach- 
ments to the broad ligament. In such instances the mucous membrane 
is pushed inward at the bends, and projects prominently into the lumen of 
the tube. Secondary changes of the epithelial lining are not unusual 
in consequence of the irritation of the retained secretions. The normal 
epithelium may be wholly lost and the lining may consist of squamous 
epithelial cells. Purely inflammatory dilatations will be referred to 
below. 

CIRCULATORY DISTURBANCES 

Active hyperemia of the mucous membrane may be a part of acute 
inflammation of the tubes, and is very frequently found at the fim- 
briated extremity in association with peritonitis. The mucous membrane 
is swollen and bright red in color. There may be excess of mucous 
secretion. 

Passive hyperemia occurs in conditions in which the general venous 
circulation in the abdomen is impeded. 

Hemorrhages into the tubes may occur physiologically during the 
menstrual period, and sometimes considerable amounts of blood are 
found under these circumstances. Small hemorrhages into the mucous 
membrane may occur in association with inflammations of the tubes 
and in the course of some of the infectious diseases. 

Hematoma of the tube, or the collection of blood in the tube, results 
from stenosis of the uterine end with accumulation of the menstrual 
discharges in the outer portions. The blood may remain in a more or 
less natural condition for a long time, or may undergo secondary changes. 
Sometimes it discharges through the abdominal end of the tube into 
the peritoneal cavity and leads to retro-uterine hematocele. 

INFLAMMATIONS 

Inflammation of the tubes, or salpingitis, may be acute or chronic. 

Acute salpingitis presents itself in several forms, such as an acute 
catarrhal and a suppurative form. In most cases the inflammation 
results from the entrance of irritants from the uterus, and the tubal 
disease is secondary, therefore, to endometritis or to other disease of the 
uterus. Among the micro-organisms discovered, streptococci, staphy- 
lococci, the Diplococcus pneumonia, and the Bacillus coli communis may 
be mentioned, but the gonococcus is by all means the most frequent 
in the non-puerperal cases. In the cases following vaginitis or en- 
dometritis, then usually gonococcal, the transition of the organisms 
is via the mucosa while in those instances when puerperal sepsis is a 
primary cause, either the mucous_membrane or deeper routes may be 



DISEASES OF THE REPRODUCTIVE ORGANS 843 

followed to reach the tube. In rare instances salpingitis may be second- 
ary to local peritonitis. 

Pathological Anatomy. — When the infecting organism enters the 
tube it passes through the isthmus which may be therefore closed very 
early, a lesion which helps to explain the retention within the tube of 
exudative fluids. In acute catarrhal salpingitis the mucous membrane 
is swollen, hyperemic, infiltrated with round cells, and covered with 




Fig. 426. — Acute septic salpingitis: section about the middle of the tube (Beyea). 

more or less abundant mucous secretion, which may distend the tube 
considerably. In the later stages the secretion is apt to become purulent. 
Interstitial inflammation with thickening of all of the layers of the 
tubal wall, is frequently a secondary result. In acute suppurative 
salpingitis the walls of the tube are infiltrated with round cells (Fig. 426), 
the mucous surface discharges abundant pus, and the tubes may become 
distended with this exudate if the abdominal and uterine ends are 
closed by the inflammatory process, acute pyosalpinx. The mucous 
membrane in these cases is intensely inflamed and often slightly ulcer- 



844 



A TEXT-BOOK OF PATHOLOGY 



ated upon the surface, or adjacent folds may be glued together to 
form pus pockets. Infective matter escaping from the fimbriated 
end involves the covering of the ovary and plastic exudate may bind it 
to the opening of the tube. If the ovary becomes infected by the pyo- 
genic cocci, tubo-ovarian abscess ap- 
pears. In case of acute suppurative 
or necrotic salpingitis secondary to 
puerperal sepsis the mucous mem- 
brane may be covered with a 
necrotic membrane; the term diph- 
theritic salpingitis has sometimes been 
applied to such a condition. 

The exudates within the tube may 
remain for a long time without change, 
or may undergo gradual inspissation, 
and sometimes even calcification 
occurs. When ulcers of the mucous 
membranes have formed, rupture of 
the tube and consecutive peritonitis 
may occur, especially during straining 
efforts, as in labor. Acute local or 
general peritonitis more frequently 
results from discharge of infective 
matter from the abdominal end of 
the tube. Localized peritonitis is 
very common in acute cases, but the 
tube rarely ruptures under ordinary 
circumstances. It seems very dis- 
tensible and localizing adhesions soon 
form, as in the case of any peritoneal 
congestion. 

Microscopically, in all forms of 
salpingitis extensive round-cell in- 
filtration is observed in all of the 
layers of the tubes. Plasma cells and 
eosinophiles are especially prominent. 

Chronic salpingitis, as a rule, 
results from the continuation of an 
acute form. The wall of the tube 
becomes thickened and the muscular 
layer is often hyperplastic. Prolif- 
erative changes in the mucous mem- 
brane are not unusual and may lead 
to actual polypoid outgrowths. Oc- 
casionally small follicular formations 
are seen in the mucosa, but ulcera- 
tions of the mucous membrane are infrequent. When the inflam- 
mation extends to the serous coat, inflammatory adhesions are fre- 
quently formed (Fig. 428), and may bind the tube firmly to adjacent 
parts and occasion great congestion or distortion. If the process has 



Fig. 427. 



-Subacute purulent gonococcal 
salpingitis. 



DISEASES OF THE REPRODUCTIVE ORGANS 



845 



not been fulminating, purulent material may remain in the tube, closed 
at both ends, for some time, thus constituting a chronic pyosalpinx. 
The closure of both ends appears at times to occur before a purulent 
stage has been reached, whereupon, instead of pus, a serous fluid ac- 
cumulates, hydrosalpinx; blood or hemoglobin added to this is called 




Fig. 428. — Chronic salpingitis: both Fallopian tubes are closed and adherent (Penrose). 

hematosalpinx. The last condition may also arise after extra-uterine 
pregnancy or by obstruction of the lumen of the uterus with retention 
of menstruation. Long standing or repeated nonpurulent salpingitis, 
or when the pus is absorbed, may leave the tube a shrunken, wrinkled, 
firm, cord-like mass. Intercurrent acute salpingitis frequently takes 




Fig. 429. — Hydrosalpinx, showing complete inversion of the fimbriae (Penrose). 

place in cases of chronic tubal disease. A focal chronic salpingitis has 
been described as occurring at the isthmus, probably being responsible 
for constant obstruction of the lumen and protracted infection of the 
submucosa. The lesion consists of firm nodules, salpingitis nodosa, 
composed of gland groups, lying in the mucosa, at times fully occluding 
the lumen. 



846 



A TEXT-BOOK OF PATHOLOGY 



INFECTIOUS DISEASES 

Tuberculosis may be most prominent as an endosalpingitis or 
as a peritoneal process in which latter case it is nearly always a part of 
pelvic tuberculosis, and bilateral. Ascending primary infection can 
hardly be proven but secondary extension from the uterus occurs. De- 
scending infection comes through the fimbriated end, being part of a 
peritoneal process, although the mucosa may be chiefly affected. Pri- 
mary tuberculosis of the tube, in the sense that no other active lesion is 
discoverable, occurs, and since at times it resembles both clinically and 
microscopically the form due to the gonocococcus, a diagnosis can be 
made only by the microscope in most instances. It is said that gonococcal 
salpingitis favors the implantation of the tubercle bacillus in the tube. 




Fig. 430. — Tuberculosis of the Fallopian tubes. The disease has extended to the perito- 
neum, which is covered with tubercles (Penrose). 

Endosalpingitis tuberculosa shows a mucocatarrhal superficial 
process overlying a densely infiltrated submucosa, in which the specific 
inflammation is irregularly developed, many scattered giant cells and 
but few typical tubercles being present. Fibrocaseous changes appear 
as a late stage. Grossly such an organ is a pale doughy mass with cheesy 
contents. The fimbriae close early, therefore producing a tuberculous 
pyosalpinx which in severe cases may destroy both mucosa and mus- 
cularis. Old cases may have fibrocaseous areas and shrunken scarred 
sections. Peritoneal tubercles may be present by extension from within 
or, being originally external, may penetrate and affect the mucosa. 

Syphilis has been observed in the form of gummata, and also in the 
form of diffuse sclerosis, in cases of congenital origin. 

TUMORS 

Fibromata and fibromyomata are met with in the external walls of 
the tubes as nodular masses. They frequently undergo secondary calci- 
fication. Lipoma occurs in the external coat lying between the layers 
of the broad ligament. 

Papillomatous elevations of the mucous membrane are quite fre- 
quent, and in some cases a transformation of papilloma to carcinoma 



DISEASES OF THE REPRODUCTIVE ORGANS 



847 



takes place. Probably most instances of primary carcinoma of the 
Fallopian tubes have this origin. These growths assume a papillary 
adenomatous or medullary structure, the former remaining within the 
tube but sending out metastases, while the latter penetrates the wall 
and spreads over the peritoneum. Secondary carcinoma may result 
from extension of uterine cancer. 

Sarcoma occurs in various forms, and syncytioma malignum may 
affect the tubes after tubal pregnancy. 

Cysts of the tubes are usually the result of localized distentions of 
the lumen in consequence of obstructions. Small cystic formations of 
obscure origin are sometimes found in the peritoneal covering of the 
tubes and along the attachment of the broad ligament. Their contents 
may be colloid or serous. 

The hydatids of Morgagni are small cystic formations about the size 
of a pea, hanging by a long pedicle at the fimbriated end of the tube. 
They are probably the result of distention of the closed end of M tiller's 
canal. 

Tubo-ovarian cysts are formed by distention of the abdominal end 
of the tubes when the fimbriated extremities are attached to the ovary, 
or in other cases may be the result of rupture of follicular cysts of the 
ovaries themselves into the abdominal end of the tubes. 

PARAMETRIUM 

The tissues below the tubes and ovaries at the sides of the uterus 
are known as the parametrium, a highly vascular area containing the 
draining elements of the pelvis. It is of great pathological importance 
in the various inflammatory lesions emanating from the lower uterine 
segment. As infection spreads from this region the parametrium re- 
acts promptly with serous, then cellular, exudate, and an acute inflam- 
matory mass arises. While it is, in a sense, a local peritonitis, the 
possibility of infective thrombosis of the large veins render spread of 
infection easy, and the chronic adhesions remaining after recovery lead to 
uterine displacements and fixative adhesions. Abscesses may spread to 
Douglas' pouch. Hemorrhages from the large vessels in the parame- 
trium may spread into this pouch or between the layers of the broad 
ligament. 

EXTRA-UTERINE PREGNANCY 

Etiology. — Any obstruction to the downward migration of the ovum 
may lead to its retention and development in abnormal situations. The 
actual cause is usually difficult to determine. Impregnation takes 
place normally in the Fallopian tube, but unless some obstruction 
arrests the passage of the ovum into the uterus, normal uterine gestation 
proceeds. The most frequent lesion responsible for hindering the 
normal descent of the ovum is chronic follicular salpingitis in which 
adhesions between the tips of the rugae and false diverticula are formed 
thus supplying recesses from which escape is difficult. Any other form 
of obstruction, as by tumors or external compression, may be included 
among the etiological factors. According to the investigations of Schu- 



848 



A TEXT-BOOK OF PATHOLOGY 



mann, ectopic pregnancy occurs in Philadelphia at the rate of one in 
every 300 pregnancies. 

Varieties and Pathological Anatomy. — The vast majority of 
ectopic pregnancy occurs in the tube but primary ovarian pregnancy 
is sometimes seen. The situation usually occupied is the isthmus just 
as the tube emerges from the uterine wall. The so-called "interstitial 
^pregnancy 11 is that in which the ovum remains in the section of the 
tube within the uterine wall. 

Tubal Pregnancy. — The changes which occur in the tube are anal- 
ogous to those met with in the uterus. The same forms of membranes 
and deciduse are developed, and a placenta develops as in the uterus 
but both are incomplete. The muscularis of the tube may hypertrophy 
somewhat, but in the end the increasing size of the contained ovum 




Fig. 431. — Tubal pregnancy, removed before rupture. The opening that has been cut in 
the tube shows the chorionic villi (Penrose). 

together with the ingrowth of the placental villi lead to thinning and 
stretching of the walls of the tube, the last factor favoring rupture. 
It is an interesting fact that the mucous membrane of the uterus forms 
a decidua of more or less complete development in cases of extra-uterine 
pregnancy (Fig. 431). 

The possible terminations of such an abnormal conception, in order 
ofntheir complexity, are as follows: 

The abnormally located ovum may die and be absorbed; this is 
possibly a common occurrence but of course its frequency cannot be 
stated. In some cases a blood clot may form which is retained as 
a mass forming the tubal mole and multiple cysts may give it the ap- 
pearance of a hydatid mole. A frequent occurrence is called tubal abortion 
and is the discharge of the ovum, through the open fimbriated end of 
the tube, into the peritoneum. The next most serious result of ex- 
tra-uterine pregnancy is the rupture of the sac into the broad ligament 



DISEASES OF THE REPRODUCTIVE ORGANS 



849 



or peritoneal cavity, with copious hemorrhage and shock. If, however, 
the fetus be of a good state of development and retain its connection 
with the placenta, pregnancy may go on to term within the peritoneal 
cavity, abdominal pregnancy. It is interesting to note that under 
these conditions separate plants of decidua may develop upon omentum 
or mesentery. Occasionally pregnancy continues in the tube, without 
rupture to full term, when, if operative measures do not remove it, 
death of the fetus occurs. 

Ovarian pregnancy is the impregnation of the ovum while still in 
the Graafian follicle. When, by reason of adhesions or perioophoritis, 
the rupture opening of the follicle is not sufficient for the proper escape 
of the ovum, it is still possible for the spermatozoon to bore in. The 
elasticity of the ovary permits the conception to proceed, even some- 
times to term. Secondary abdominal pregnancy may follow the ovarian 
form. 

Because of the penetration of the fetal villi into the depths of the 
tubal mucosa and into blood spaces, hemorrhage is common in tubal 
pregnancy. The blood may go into the tube or escape into the broad 
ligament, in either case forming a hematoma. When sudden and severe, 
it usually gets into the peritoneum and collects in the pelvis. The 
irritation incident to rupture and the collection of blood lead to ad- 
hesions which may surround and wall off the blood, thus forming a , 
hematocele. Secondary bacterial infection may lead to suppuration. 
Because of the abnormal position of such ectopic ova the blood supply 
is usually incorrect and death occurs, followed by absorption, or cystic 
degeneration, suppuration or calcification. In abdominal pregnancies 
perhaps most frequently, but also in others, the fluid may be absorbed 
after fetal death and the remaining mass become impregnated with 
lime salts, lithopedion. Such mummified fetuses have been known to 
be discharged via the vagina or rectum. Chorion epithelioma frequently 
follows tubal pregnancy. 

The Vagina 
prolapse of the vaginal walls 

Prolapse of the anterior or posterior wall of the vagina may be due 
to abnormal relaxation of the tissues, or it may be secondary to pro- 
lapse of the uterus and similar conditions that press the vaginal walls 
downward. Not infrequently the posterior wall of the bladder is dragged 
downward with the anterior wall of the vagina, and vaginal cystocele 
results. Similarly, the anterior wall of the rectum may be carried down- 
ward with the posterior wall of the vagina; this is termed vaginal recto- 
cele. Bulgings of the vaginal walls may be passive on their part, 
resulting in such cases from dilatation or loss of support on the part 
of the rectum or bladder. Erosions and ulcerations are apt to occur 
on exposed protruded surfaces. 

STENOSIS OF THE VAGINA 

Congenital stenosis is rare. More frequently the lumen of the 
vagina is narrowed by contraction of cicatricial tissues formed in in- 
flammatory diseases of the walls, or by adhesion of the opposite surfaces 

54 



850 



A TEXT-BOOK OF PATHOLOGY 



following ulcerations. Complete occlusion may occur in the latter form 
of cases, especially in old women. Atresia leads to obstruction of the 
discharges from above, and when menstruation is due causes collection 
of blood in the vagina (hematocolpos) and in the uterus (hematometra) . 

WOUNDS AND FISTULA 

Injuries to the vaginal walls may be caused by the insertion of sharp 
bodies or instruments, or by coitus. Much more frequently injuries 
are due to stretching or pressure during labor. Superficial lacerations 
caused by overdistention are frequent, but more extensive injuries may 
be caused by prolonged pressure of the infant's head or by instruments 
used in delivery. In such cases infection and phlegmonous inflamma- 
tion are prone to occur, and vesicovaginal, urethrovaginal, or recto- 
vaginal fistulse are sometimes the result. The urine or feces may be 
discharged through the vagina, and often cause secondary inflammations 
of the entire vaginal mucosa. 

Similar fistulae may be due to ulcerative processes of other kinds, 
to necrosis of carcinomata of the vagina, or to diseases of the bladder or 
rectum. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs in the early stages of inflammation. The 
mucous membrane is light red in color and a little swollen. 

Passive hyperemia is frequent in pregnancy, and occurs in conse- 
quence of pressure due to other causes, such as uterine tumors and the 
like. The mucosa becomes swollen and edematous, and may be moist 
from increased secretions. 

Hemorrhages into the vaginal walls are most frequently due to 
traumatism. Inflammation and ulceration may result from the hemor- 
rhagic extravasation. 

INFLAMMATIONS 

Acute Catarrhal Inflammation, Vaginitis, or Colpitis. — This 
condition is frequently due to gonorrheal infection, but may result from 
other causes, such as mechanical and chemical irritants, or in young 
girls from the invasion of the Oxyuris vermicular is from the rectum. 
The mucous membrane is usually deeply congested, and the surface is 
covered with mucopurulent exudate. In gonorrheal cases the cervix 
uteri and urethra are, as a rule, coincidently affected. The vagina 
seems well prepared to resist infection, at least in the adult, sojthat 
inflammation is usually preceded by some congestion or trauma which 
either reduces resistance or introduces the pathogenic germs. The 
viscus is rarely primarily or solely diseased, the vulva or cervix commonly 
presenting the initial trouble. 

Exfoliative Vaginitis. — In rare cases of intense catarrhal vaginitis, 
in which the deeper layers of the mucosa are principally involved, 
membranous formations, consisting of parts of the superficial epithelial 
layers, may be discharged. 

Pseudomembranous vaginitis may occur in association with 
various infectious diseases, such as pneumonia, pyemia, cholera, etc.; 



DISEASES OF THE REPRODUCTIVE ORGANS 



851 



but it is more frequently the result of pressure-necrosis and infection 
occurring during labor, and is one of the lesions of puerperal sepsis. 
The surface of the vagina is more or less extensively covered with a 
dirty and exfoliating pseudomembrane. After discharge of the latter 
ulcerations are often formed. Extensive necrosis of the vaginal walls 
may occasion great destruction, and in some instances phlegmonous 
inflammations of the perivaginal tissues may cause separation of the 
mucosa. 

Other forms of vaginitis are erysipeloid, aphthous, and emphysema- 
tous. They are not peculiar in manifestation, but show the usual 
characters of these infections. The indentity of the last has been ques- 
tioned. It is supposedly due to an anaerobic organism and is common 
after labor. 

Chronic catarrhal vaginitis may be the continuation of an acute 
inflammation, or may occur in a gradual manner in women reduced 
in vitality. The mucosa usually presents appearances somewhat like 
those of acute cases, though the congestion is less marked. Abundant 
mucopurulent or mucous discharge (leukorrhea) may be present. 
Erosions of superficial epithelium and enlargements of the lymphoid 
follicles are sometimes observed. In long-standing cases the surfaces 
may be smooth and the entire mucosa somewhat indurated (senile 
vaginitis) . In all forms of long duration, more or less complete erosions 
occur which may lead to scar formation. This having occurred, cicatricial 
stenosis or atresia arises. 

Kraurosis vulvae is primarily a hyperplasia then an atrophy of 
the vulvar and vaginal epithelium and subcutaneous connective tissue. 
The former becomes squamous by atrophy of the rete while the latter 
shows hyaline changes, the elastic fibers disappearing and the papillae 
flattening out. When the epithelium remains active and rather hyper- 
plastic, a condition of leukoplakia appears; little connective tissue change 
occurs in this form. The appearance is of a hard, dry, glistening, pale, 
cutaneous vulvar and vaginal surface, often in folds or showing cracks. 
The labia atrophy and may disappear while hairs fall out and areas 
devoid of pigment are seen. In severe cases contraction of the out- 
let may occur. The cause is obscure but it is most often seen in middle 
life after a history of prolonged leukorrhea. Severe pruritus is an al- 
most constant accompaniment. Epithelioina occasionally succeeds upon 
both the above conditions. 

Elephantiasis of the labise or clitoris may be congenital, or may 
result from local inflammatory conditions or obstructions of the lymph- 
channels. The affected parts are sometimes enormously enlarged. 
The surface is smooth or nodular and is gelatinous or hard in consistency. 
As elsewhere, the histology is that of a fibrous overgrowth with lymph- 
ectasia. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of ulcers associated with uterine 
tuber culosis, or in the form of lupus from extension of the latter from 
the vulva. 



852 



A TEXT-BOOK OF PATHOLOGY 



Syphilis. — Chancres, mucous patches, and simple inflammation may 
occur in any part of the vagina, and circumscribed (gummatous) or 
diffuse infiltrations have been described. 

TUMORS 

Fibroma and myofibroma may arise in the muscular layer of the 
vaginal wall, and may project as nodular masses or assume a polypoid 
form. 

Sarcoma may occur as a circumscribed mass, but more commonly 
as diffuse infiltration or grape-like masses, which tend to ulcerate. 
These latter, seen most often in children, not infrequently are teratoid 
in that both kinds of muscle, myxoid and adult connective tissues, with 
sarcomatous changes, comprise the masses. Although growing outward 
as a cauliflower mass, they also tend to infiltrate deeply. 

Papillomata are not infrequent, in the form of small warts or as 
considerably elevated condylomata. 

Carcinoma of the vagina is most frequently secondary to cervical 
cancer. Similarly, it may follow cancer of the vulva. Primary car- 
cinoma of the vagina is rare. It occurs in the form of a circumscribed 
villous projection. When primary it is usually squamous, when second- 
ary it may be glandular, in type. 

Cysts of the vaginal walls vary in size and number. Frequently 
they are multiple, and the size ranges from scarcely discoverable cavities 
to those the size of an egg. The contents are usually serous and color- 
less, or, less frequently, of brownish color. In some instances a flat epi- 
thelial lining has been discovered. The origin of these cysts is probably 
variable. Some seem to arise from remnants of the lower end of 
Gartner's duct; others are probably lymphangiectatic. The multiple 
small cysts sometimes occurring in pregnancy are due to follicular 
distentions, or to small hemorrhages with subsequent cystic change. 

The Vulva 

The most common anomalies of the vaginal entrance take the form 
of hypertrophy, particularly of the clitoris, but also of the labia, of 
hypoplasia combined with imperfect development higher in the geni- 
talia, of reduplication or fusion of the labia, and of imperforate hymen, 
or one with several openings. Hernia may occur into a patent canal 
of Nuck in the labia majora. 

WOUNDS 

Injuries of the vulva frequently occur during labor. Laceration 
of the fourchettcis very common, and in a considerable proportion of 
cases more extensive tears extending into the perineal body, and some- 
times through this into the rectum, are observed. Prolonged pressure 
and contusion during labor may occasion hemorrhages into the tissues 
of the vulva. 

CIRCULATORY DISTURBANCES 
Active hyperemia is met with in acute inflammations. 
Passive hyperemia and edema occur in conditions in which there 
is general venous stasis, as in cardiac or pulmonary disease. They 



DISEASES OF THE REPRODUCTIVE ORGANS 



853 



are also met with in pregnancy. The vulva is dark red in color, some- 
times cyanotic; the subcutaneous and submucous tissues become edem- 
atous, and in consequence the labia majora may swell enormously. 

Hematoma of the vulva is caused by compression and contusion 
of the vulva during parturition, or less frequently at other times. Vari- 
cosity of the veins is a predisposing cause of importance. Considerable 
masses of blood (" thrombi") accumulate in the submucous tissues 
of the vulva and vagina. These may be subsequently absorbed, or they 
may discharge through the skin in consequence of superficial ulcerations 
and ruptures. Infection of the thrombus may cause abscess of the 
labia or other affected parts. 

INFLAMMATION 

Acute catarrhal inflammation results from the same causes as 
occasion acute vaginitis. The pathological appearances are, in general, 
the same, though edematous swelling is likely to be more, marked. Dis- 
tention of the glands of Bartholin and secondary abscess-formation 
in these glands are common conditions in gonorrheal vulvitis. Vulvitis 
may be of erysipelatous form, upon which gangrene may supervene. 
Noma has been observed on the external female genitalia. 

Epidemic vulvovaginitis of children, in all probability due to the 
gonococcus, appears frequently in hospitals and other institutions. 
The origin and method of spread are often obscure, and the disease is 
very difficult to eradicate. The symptoms and signs may intermit, 
but in their absence the person remains infective. 

Chronic inflammation sometimes follows acute vulvitis. Con- 
siderable hyperplasia of the mucosa is sometimes the result. Erosions 
and ulcerations are less frequent. Kraurosis vulvae is similar to that 
described under the vagina but at times seems rather limited to the 
exposed parts. 

Phlegmonous inflammation, or abscess, of the submucous tissue 
of the labia majora sometimes results from extension of a similar proc- 
ess in the adjacent parts, or may be the direct result of injuries and 
hematoma, with secondary infection. Esthiomene is a long-continued 
ulcerative vulvitis of obscure origin, resembling a rodent ulcer. About 
the rather symmetrically disposed lateral ulcerations, the tissues are 
swollen and covered with a foul pus. It resembles lupus and cancer 
and resists treatment. 

INFECTIOUS DISEASES 

Diphtheria sometimes attacks the vulva, especially in puerperal 
women. The pathological conditions are similar to these observed in 
other mucous membranes. 

Tuberculosis may occur in the form of lupus. The lesions are 
irregular ulcers with elevated edges and more or less necrotic bases. 

Syphilis. — Chancres and mucous patches are met with on the sides 
of the labia and elsewhere. Condyloma acuminatum, or venereal wart, 
is frequently seen upon the vulvar surfaces but it tends to grow in 
spreading clusters that may extend over the perineum and around the 



854 



A TEXT-BOOK OF PATHOLOGY 



anus. Gonorrhea certainly precedes enough of the growths to be of 
some etiological importance, although they may occur without this 
disease. Histological study shows it to be a hypertrophy of the dermal 
papillae with hyperplasia of all layers of the epiderm. 

Chancroids occur in the same situations as chancres. Very often 
opposite sides of the vulva are involved by attrition. 

Gangrene of the vulva may be the consequence of severe contusions 
or inflammations occurring in the course of various infectious diseases. 

TUMORS 

Fibroma, fibromyxoma, and myofibroma are occasionally met 
with as nodular tumors or poh^ps arising from the labia majora. Lipoma 
and sarcoma may present a similar macroscopical appearance. All 
of these growths are rare. 

Elephantiasis vulvae is a not infrequent affection, especially in 
eastern and tropical countries. It may be due to congenital dilatations 
of the lymphatic channels, or to lymphangiomatous tumor-growths. 
More frequently elephantiasis is caused by filarial and inflammatory 
conditions that occasion obstruction to the flow of the lymph. In some 
instances the etiology is very obscure. 

Pathologically, elephantiasis consists of a thickening of the subcu- 
taneous connective tissue, with more or less involvement of the skin as 
well. The disease may begin in the clitoris, or in one or other of the 
labia, and may be confined to the part primarily affected, or may extend 
to other parts. The affected portions are tough and edematous; the 
skin is tightly bound to the subcutaneous tissue. The surface may show 
dermatitis, but in some cases is smooth. Superficial ulcers may occur, 
and sometimes the dilated lymph-channels communicate with the sur- 
face, discharging lymph (lymphorrhea). 

Papillomatous tumors are not infrequent in syphilitic women 
in the form of elevated condylomata. A somewhat analogous condi- 
tion of obscure etiology is that termed caruncle. It presents itself 
as a papillomatous, deep red elevation at the meatus of the urethra, 
constructed usually on an angiomatous basis, covered with squamous 
epithelium. Occasionally it will be made up of purely granulation 
tissue or quite rarely of adenoma-like structures. 

Adenoma arising from the glands of Bartholin has been described. 

Carcinoma is uncommon but usually quite malignant, giving early 
metastasis to the groin. It most frequently arises from the clitoris, 
but may affect any portion. Glandular cancer may begin in Bartholin's 
glands. 

Cysts are quite frequent. Small retention-cysts, containing pul- 
taceous (atheromatous) matter, are sometimes met with in the labia 
majora, and in the great majority of cases are retention-cysts of the 
glands of Bartholin. Larger cysts, containing serous or somewhat blood- 
stained liquid, may result from hematomata, or may be lymphangio- 
matous in origin. Hydrocele of the canal of Nuck has the superficial 
appearances of a cyst of the labia. 



DISEASES OF THE REPRODUCTIVE ORGANS 



855 



The Decidua, Placenta, and Fetal Membranes 

Anatomical Considerations. — The fetus is enclosed within a deli- 
cate fibrous membrane, the amnion, and this is covered with a second 
membrane, the chorion. After the deposit of the ovum in the uterus 
the mucous membrane of the latter undergoes a form of hyperplasia, in 
which the uterine glands and the blood-vessels take part conspicuously, 
and thus the organ becomes lined with a thickened mucosa. The latter 
is termed the decidua vera. A reflection from this covers the fetus en- 
closed in its membranes, the reflection being known as the decidua 
reflexa. At about the fifth month of development the decidua reflexa 
and the decidua vera unite and fuse. The portion of the decidua vera at 
which the placenta is subsequently located is termed the decidua sero- 
tina. In this portion the vascular system is particularly marked, and is 
composed of large venous sinuses with thin walls. The fetal chorion 
carries on its outer surface numerous small projections, or villi. In the 
region of the decidua serotina these villi undergo marked hyperplasia 
and bury themselves between the venous sinuses of the decidua. At 
the junction of the villi and the decidua two layers of cells are developed. 
The first, immediately covering the villi, consists of cubical epithelial 
cells (Langhan's cells). Outside of these, and uniting the villi with the 
maternal tissue, is a layer of clear protoplasmic material containing 
large nuclei. This has the appearance of nucleated protoplasm, rather 
than that of collections of cells of definite outline. This protoplasmic 
layer, syncytium, is probably, like Langhans' cells, derived from the 
covering of the chorionic villi, though some authorities contend that it is 
maternal in origin. The anatomical characters of the placenta of im- 
portance in its pathology are the clear glistening amnion that is reflected 
over its exterior, the delicate gray membrane, derived from the decidua, 
lying on the uterine side, the rather regular circumferential venous 
sinus, the delicacy of the villi on the separated surface and the pale 
pink myxoid tissue making up the body of the afterbirth near the 
insertion of the umbilical cord. 

ABNORMALITIES OF DEVELOPMENT 

The Placenta. — Abnormal smallness of the placenta, or hypoplasia, 
and abnormal largeness are occasionally observed. More frequently 
an adventitious placenta (placenta succenturiata) may be attached to the 
main placenta or may lie near it. Abnormal location of the placenta 
at or near the neck of the uterus (placenta prcevia) is an important condi- 
tion, from its liability to cause hemorrhage and miscarriage. 

The Umbilical Cord. — Occasionally the cord is divided near its 
placental end into two or more branches. The placenta may be corre- 
spondingly divided or single. The attachment to the placenta may be 
marginal instead of central, and sometimes the blood-vessels spread out 
into a broad marginal attachment, with absence of their gelatinous 
covering. The latter is termed velamentous insertion. 

Abnormalities of the blood-vessels, such as branching, a single 
artery, two veins, etc., are unimportant. 



856 



A TEXT-BOOK OF PATHOLOGY 



Twists and knots of the cord are frequent, and may strangulate 
the cord and stop the circulation, causing death of the fetus. 

Thickening of the intima of the umbilical vein and of the adven- 
titia of the arteries is probably syphilitic in nature. 

CIRCULATORY DISTURBANCES 

Hydrorrhea gravidarum is a condition in which abundant serous 
or somewhat turbid liquid is secreted from the deciduse from catarrhal 
inflammation, or it may represent the emptying of a hydrosalpinx; 
the same picture can be found when the membranes rupture but preg- 
nancy continues. In all cases abortion or miscarriage is not unusual. 

Edema of the placenta results from obstruction to the umbilical 
vein or occurs with edema of fetus and deciduse. Edema of the amniotic 
sac, hydromnios, is due to excessive secretion or failure of absorption. 

Hemorrhages from the decidua or into the decidua and placenta 
are not infrequent. Hemorrhages from the surface may be due to pre- 
ceding decidual disease, to violence, or to congestions of any origin 
which can lay the foundation for thrombosis in large blood spaces of 
the decidual area. Small hemorrhages may remain as clots, then 
occasionally causing one form of mole, may absorb or may remain as 
a serous cyst. Large hemorrhages may cause rapid discharge of the 
uterine contents. In cases of that abnormal position of the placenta 
called placenta prsevia hemorrhages are frequent. Escape of blood 
into the body of this organ is called placental apoplexy. The causes 
and results are as given above. There arises in this condition a dis- 
tinct mass of blood, hematoma, or a diffuse infiltration shaped more 
or less like a true infarction. 

Fleshy moles or polypi are the terms used to designate formations in 
the deciduse and placenta resulting from gradual hemorrhage and de- 
struction of the ovum. The hemorrhage takes place in the decidua, and 
then extends between the chorionic villi into the fetal membranes, which 
may be more or less extensively torn apart. Irregular masses of clotted 
blood attached to the placental site and to the chorion are discovered. 
The amniotic cavity contains viscid fluid and the ovum is more or less 
completely disorganized. Sometimes no recognizable remnants can be 
found. The moles may be retained a long time and may undergo 
secondary calcareous infiltration. Usually they are soon discharged. 

Placental Infarcts. — This term is applied to light-colored, more or 
less indurated areas met with in the placenta, deciduse, and sometimes 
in the chorion. The nature of these formations is still somewhat 
uncertain. They are composed of fibrin of reticulated or granular char- 
acter, with occasional areas of softening and hemorrhagic accumula- 
tions, and are not rarely surrounded by a zone of cellular infiltration. 
Some of these "white infarcts " may be only an exaggeration of the 
normal coagulation necrosis occurring toward the end of pregnancy. 
Some are surely due to hemorrhages. When they are extensive it is very 
probable that they represent results of disturbances of circulation 
caused by thickening of the walls of the blood-vessels. 

Degenerations of the placenta are not common nor of great pathological 
interest. It is noteworthy however that calcification occurs normally, 



DISEASES OF THE REPRODUCTIVE ORGANS 



857 



toward the end of gestation, in the villi and subjacent tissue. When it 
extends deeply, following vessels, it is pathological, and is usually due 
to anemia or intoxications. Fatty change is unusual beyond that 
occurring physiologically at term. Myxomatous and dropsical changes 
are rare. 

INFLAMMATION 

Inflammations of the placenta (placentitis), of the chorion villi, 
or of the decidua (endometritis decidualis) may occur in association with 
preceding diseases of the uterus, and especially in cases of syphilis of 
the mother or fetus. The inflammation takes the form of cellular in- 
filtration and induration. This may begin in the decidua and extend to 
the placenta, and may be of a diffuse or circumscribed character. The 
villi of the placenta may be greatly compressed by the inflammatory 
tissue, and may suffer fatty degeneration and atrophy. In other cases 
the inflammatory changes are most pronounced in the walls of the 
blood-vessels and around the vessels of the chorion and umbilical cord. 
Nodular thickening or diffuse induration results, the latter especially in 
cases in which coincident involvement of the chorionic villi has occurred. 

Diffuse hyperplasias of the decidua are sometimes described as endo- 
metritis decidualis, and while most of them may be overgrowths, there 
are many showing infiltration and exudation bringing them within the 
category of inflammation. Such a true inflammation has been seen in 
the pregnant uterus during eruptive infectious diseases. Pathologically 
the lesion may be catarrhal, purulent, hemorrhagic, cystic or polypoid. 

INFECTIOUS DISEASES 

Tuberculosis of the placenta was suspected as a possible condition 
long before positive demonstrations were made. In recent years, 
however, a number of undoubted cases have been described. Macro- 
scopically, there may be but little change in the appearance of the 
affected parts. 

Small tubercles, containing giant cells and tubercle bacilli, first 
appear in the decidua serotina, and later invade the placental and 
chorionic tissues between the villi. The epithelial covering of the villi 
undergoes hyperplasia, forming collections of large cells. Warthin 
says that the decidual cells do not form tubercles, the tubercle bacillus 
being primarily necrotizing to the placental cells, but that the fixed 
tissue elements in the neighborhood supply cells for the tubercle. In 
the later stages of the process caseous necrosis of the tuberculous struc- 
tures takes place, and the villi themselves suffer invasion and degenera- 
tion. Their blood-vessels are frequently occluded by hyaline thrombosis 
and proliferation of the endothelial lining. Tubercle bacilli have been 
demonstrated in the vessels of the fetal side of the placenta, though 
less frequently and abundantly than in the maternal vessels. 

Syphilis of the placenta may take the form of a diffuse hyperplasia, 
or of a nodular or gummatous process. The placenta is enlarged, in- 
durated, and heavy; it is light colored, in localized areas or diffusely. 
Microscopically, cellular proliferation springing from the adventitia of 
the blood-vessels is the characteristic feature. The epithelial cells 



858 



A TEXT-BOOK OF PATHOLOGY 



covering the villi may proliferate, and fatty degeneration of the body of 
the villi is not infrequent. The chorion and amnion may be diffusely 
thickened. The syphilitic nature of cases conforming with the above 
description is often doubtful, as is also the nature of some of the cases of 
placentitis that are often described as syphilitic. 

HYPERPLASIA 

Occasionally, diffuse or circumscribed thickening of the deciduae 
occurs in association with chronic metritis; the term endometritis decid- 
ualis is applied to this condition. (See Inflammation.) 

Placental Polypi. — Portions of the decidua, and especially the 
placenta, retained in the uterus, may remain firmly attached and may 
undergo subsequent proliferative change, forming polypoid tumors of 
adenomatoid structure. These are particularly frequent after abortion. 

Destructive Placental Polyps. — Like the preceding, these origi- 
nate in retained portions of the placenta, but differ in the more active 
proliferative changes that take place. On the uterine surface they 
are covered with fibrin and blood-clots, and at their attachments are 
composed of variously formed cells, including large epithelium-like 
cells enclosed in a vascular stroma. The growth may involve the uterine 
tissues to a considerable extent. Its nature is obscure in some particu- 
lars, but resembles that of the syncytioma. 




Fig. 432. — Section of a hydatid mole. 



Hydatid moles present themselves as rounded, rather translucent 
bodies hanging by their pedicles to the outer surface of the chorion, 
and often attached one to another in clusters, resembling a bunch of 
grapes. Microscopically, they are found to be composed of myxomatous 
or more or less edematous fibrous tissue containing few cells and free 
nuclei, and covered on the outer surface by epithelial cells (Fig. 432). 
The nature of the hydatid mole has been the subject of some controversy. 
Virchow taught that they are simply myxomatous hypertrophied chor- 
ionic villi. More recent investigators have found evidences of active 
hyperplasia of the superficial epithelium of the chorion villi, with second- 



DISEASES OF THE REPRODUCTIVE ORGANS 



859 



ary degeneration, edema, and necrosis.. This accounts for the fact 
that sometimes the moles extend deeply into the decidua, and even 
into or through the muscular wall of the uterus. 

Hydatid moles are especially met with in women suffering from 
chronic constitutional diseases (nephritis, anemia) and in those becom- 
ing pregnant late in life. Endometritis seems to bear some relation, 
though the disease is evidently one of the fetal rather than maternal 
tissues. This is shown by the limited extent of the disease in some cases, 
and by the fact that in twin pregnancy the membranes of only one of 
the fetuses may be affected. When the disease is extensive death of the 
fetus usually results, and the moles are discharged in the form above 
described, or enclosed in clotted blood. 

Syncytioma malignum, while discussed already under tumors, is of 
especial importance at this point because of its frequency after moles. 
When it is recalled how intimately the syncytial cells are involved with 
the vessels and deeper layers of the decidua serotina, which it is alleged 
they are able to penetrate by the action of a proteolytic ferment, it 
will be more easily seen how they may continue to grow in an abnormal 
situation if they are no longer needed in the ordinary progress of placental 
and fetal development. Since they are able to penetrate vessels, an 
explanation is reached for tumors from them and the Langhans' cells, 
arising at other situations. Variations in the histology are common, 
examples in which either the Langhans' epithelium or the syncytial 
cells predominate, being encountered. These new growths are ex- 
ceedingly malignant by metastasis, extension, toxemia and hemorrhage. 

The Penis and Scrotum 
congenital abnormalities 

Absence of the penis is rarely observed; more frequently it is abnor- 
mally small, resembling the clitoris of the female. Occasionally the 
organ is doubled, each half containing a duct, one for the discharge of 
urine, the other for seminal fluid. 

Hypospadias is the condition in which the urethra terminates in 
an orifice on the under surface of the penis, in the pendulous portion or 
at the bulb, or occasionally at the root of the scrotum or in the peri- 
neum. With hypospadias there is usually some deformity of the scro- 
tum, the commonest being a division into lateral halves containing 
the testes, or the latter may be in the inguinal canal or abdomen. Epi- 
spadias is a less frequent condition; the urethral orifice in this case is 
found upon the dorsal side of the organ. Excessive length of the prepuce 
is a frequent abnormality; there may be associated with this stenosis of 
the preputial opening, so that the glans penis cannot be exposed {phi- 
mosis) . 

The condition of hermaphroditism, or the presence of the genital 
organs of both sexes in one individual, is rare, while pseudohermaphrodi- 
tism is more common. In the latter the genitalia are distinctly of one 
sex, although anomalous in formation, while the secondary sexual 
characters are those of the other sex. 



860 



A TEXT-BOOK OF PATHOLOGY 



INFLAMMATION 

Inflammation of the mucous membrane of the glans penis 
(balanitis) or of the prepuce (posthitis) is not infrequent. Among the 
more frequent causes are uncleanliness, with decomposition of smegma 
retained beneath the prepuce, irritation by the urine in cystitis or other 
inflammatory diseases, gonorrheal infection, and chancroids. The 
mucous membrane becomes swollen and red, and considerable purulent 
exudate may be discharged. Edematous swelling of the prepuce is 
frequent, and may cause inability to retract the prepuce over the glans 
(phimosis). In other cases the prepuce, previously drawn back, be- 
comes so tensely swollen that it cannot be pushed forward to its normal 
position (paraphimosis) . 

In catarrhal inflammation of the prepuce there may be associated 
retention-cysts of the mucous glands, or it may assume an eczematous 
form with a herpetoid eruption, in both of which cases the condition 
is prolonged or recurrent. The cysts may rupture, causing small ul- 
cerations. The inflammation may take a membranous or phlegmonous 
form; these may lead to phagodenic ulceration or gangrene and may 
extend to the body of the organ. 

Inflammation of the cavernous bodies may result from trauma- 
tism, or from extension of gonorrheal urethritis, and may sometimes 
occur in infectious diseases, such as small-pox, pyemia, etc. The penis 
swells considerably, and abscesses or diffuse purulent infiltration may 
result. In traumatic cases with hemorrhagic exudation necrosis or 
gangrene may result. In case of favorable termination after severe 
inflammations deforming cicatrization may occur, due to the formation 
of fibrous tissue in nodules or cords, most often on the dorsum but also 
where an injury has been localized. 

INFECTIOUS DISEASES 

Syphilitic chancres and secondary lesions and soft chancre or 
chancroid are frequently located upon the prepuce or its frenum, or 
upon the glans penis. (The lesions are described in Part I.) 

Tuberculosis is a rare condition in this situation. It has been 
met with in the form of necrotic ulcerations. It is very likely that 
direct infection of the penis may occur during coitus with a woman who 
has genital tuberculosis. In children it has been attributed to the prac- 
tice in certain rituals of smearing the wound of circumcision with saliva. 

TUMORS 

Papilloma, or condyloma acuminatum, is not infrequent on 
the glans penis and prepuce. Sometimes it has a distinctly inflam- 
matory origin, occurring in association with gonorrhea, syphilis, or 
other forms of local irritation; in other cases it originates without dis- 
coverable cause. There are usually several or many warty elevations, 
and occasionally a mass of warts is aggregated in a cauliflower fashion. 
Microscopically, condylomata are composed of a stroma of vascular con- 
nective tissue covered with hyperplastic epithelium. The cauliflower- 
form may be distinguished from epithelioma by observing that the 



DISEASES OF THE REPRODUCTIVE ORGANS 



861 



mucous membrane is not infiltrated and is movable upon the underlying 
tissues. 

Carcinoma (epithelioma) of the penis may arise from the glans or 
from the prepuce. It may present itself as an infiltrating growth with 
a tendency to ulceration, or as a papillomatous, cauliflower-like growth. 
In the latter case the primary growth is either papillomatous, with sec- 
ondary carcinomatous alteration, or carcinomatous, followed by papillo- 
matous outgrowths. Cpnsiderable destruction of the glans penis may 
occur, and metastatic nodules are frequently formed in the inguinal 
glands but widespread secondary tumors are rare. 

Epithelioma of the scrotum is comparatively frequent in chimney- 
sweeps and paraffin-workers. It may be warty, ulcerative or infil- 
trating and does not metastasize freely. 

Elephantiasis of the scrotum is a common disease of the East. 
The scrotum may be enormously enlarged. Some cases are due to 
filariasis, while others are the result of lymph stasis from cicatrices or 
chronic lymphangitis. Somewhat similar thickening of the prepuce 
is a rare condition. 

Cysts. — Small cysts, due to occlusion of the glands of the mucous 
membrane and of the skin, are occasionally met with under the prepuce 
and in the scrotum. Dermoid cysts of the scrotum are occasionally 
observed. 

Lipomata, angiomata, and fibromata are rare forms of tumors 
of the penis. 

Concretions beneath the prepuce result from phimosis with reten- 
tion of the smegma. Sometimes they increase by constant additions 
until they reach considerable size (200 g.). In one case seen by one of 
us gouty tophi in the prepuce grew to the size of a small lemon. 

INJURIES OF THE PENIS 

Direct traumatism may occasion serious laceration of the corpora 
cavernosa, especially when the penis is erect at the time of injury. Con- 
siderable hemorrhagic extravasation may occur, and inflammation 
or even necrosis and gangrene may ensue. Fracture of the penis is a 
term applied to rupture of the fibrous capsule of the cavernous bodies. 
Both this and less extensive lacerations occasion great hemorrhagic 
swelling, with subsequent inflammation or necrosis. Injuries to the 
penis may cause rupture of the urethra, with extravasation of urine. 

The Testicles 
anatomical and physiological considerations 

The testicles are composed of tubules lined with cells, spermato- 
gonia, from which the spermatozoa are derived, and of certain interstitial 
cells (cells of Ley dig) which form a somewhat distinct glandular system. 

Aside from its relation to the reproductive function accomplished 
by the production of spermatozoa, the testicles, as the ovaries in the 
female, have an important bearing on growth and metabolism. Early 
castration leads to eunuchism, in which bodily growth, and especially 
fatty deposition, may be excessive, while infantile characteristics and 



862 



A TEXT-BOOK OF PATHOLOGY 



the arrest of development of certain accessory organs of sex are marked. 
Sometimes tumors of the testicles have occasioned precocious develop- 
ment. These effects are attributed to removal or stimulation of the 
function of the interstitial cells rather than of the tubular cells. The 
adrenals, hypophysis, and pineal gland seem to exercise some influence 
upon the testicle. 

CONGENITAL ABNORMALITIES 

Absence of one or both testicles is a rare condition. More fre- 
quently the organ is hypoplastic, remaining undeveloped through life, 
the man being infantile or effeminate. Polyorchism occurs at times. 

The most frequent congenital abnormality is cryptorchismus, a con- 
dition in which one or both testicles remain in the abdominal cavity, 
in the inguinal canal, or elsewhere in the tract through which normal 
descent occurs. The undescended testicle may descend at or before 
puberty, or may remain fixed in its abnormal position. In the latter 
case, especially if the testicle is in the inguinal canal, secondary inflam- 
mation or atrophy may occur. Slight defects in the development of the 
testicle are not infrequent, but are unimportant. The causes of cryp- 
torchismus are numerous, the most common being arrest of development, 
antenatal peritonitis, and a disproportion between the size of the organ 
and of the inguinal canal. Unless degenerative, inflammatory or 
neoplastic change occur, the organ need not be sterile. If atrophy occurs, 
however it affects principally the spermatocytes and not the interstitial 
elements so that male characters usually develop correctly. 

ATROPHY AND HYPERTROPHY 

Atrophy may follow any form of inflammation of the testicle or 
epididymis, such as those occurring after gonorrhea, mumps, and other 
infectious diseases or traumatism. In other instances pressure upon 
the organ, as in hydrocele, tumors, etc., is the cause of atrophy. Atrophy 
also may occur in cryptorchism or when, by stricture of the vasa or 
ejaculatory ducts, semen is retained in the testes. Any of the above 
conditions, operative in early life, may lead to aspermia and sterility. 
The most frequent form of atrophy is that which occurs as a natural 
process of involution in old age {senile atrophy) . 

The testicle decreases in size, increases in consistency from over- 
growth of connective tissue, and is usually more pigmented than in 
health. Microscopically, the seminal tubules are found to have under- 
gone fatty degeneration and contain fatty debris and blood-corpuscles. 

Hypertrophy of one testicle may occur as a compensatory process 
in cases of disease, atrophy, or removal of its fellow, and after disease 
of the adrenal cortex. Hypertrophy of this sort has been produced 
experimentally in animals. The seminal tubules increase in size, but 
are otherwise normal. 

DEGENERATIONS 

Fatty degeneration is frequently observed in testes subjected to 
pressure through tumors or other pathological conditions, and in cases 
of atrophy of the testicle from any cause. The epithelium of the tubules 



DISEASES OF THE REPEODUCTIVE ORGANS 



863 



is attacked and may be completely destroyed, with production of fatty 
detritus. 

Myxomatous degeneration occurs in various tumors of the testis 
and in gummata. 

Calcification may affect old inflammatory deposits, especially 
those of the epididymis. 

Caseation is a frequent condition in tuberculous and syphilitic 
lesions; and abscesses may undergo a process of inspissation, with 
formation of dry, caseous material. 

CIRCULATORY DISTURBANCES 

Active hyperemia of the testis, epididymis, and especially of the 
membranes, occurs in association with acute inflammations. 

Passive hyperemia is caused by pressure upon the veins or dis- 
ease of the veins (varicosity). The testis and epididymis become swollen 
from edema, and, if the hyperemia persists, fatty degeneration and 
atrophy may result. Serous effusion into the tunica vaginalis (hydro- 
cele) may be purely dropsical, but is more frequently inflammatory 
(see page 865). 

Embolism of the spermatic artery may occasion hemorrhagic 
infarction, followed by necrosis or gangrene of the testis. This sequence 
has been observed in a few cases, and has been proved experimentally. 
Sometimes gangrene seems to be caused by phlebitis of the pampiniform 
plexus. 

INFLAMMATION 

Inflammation may involve the testis (orchitis), the epididymis (epi- 
didymitis) , or the tunica vaginalis (vaginitis testis) . 

Etiology. — Traumatism is a frequent factor in the etiology, and 
causes inflammation of the epididymis and membranes more frequently 
than of the testicle itself. Blows, bruises, and contusions are the usual 
conditions that cause this form of inflammation. 

In another group of cases the irritants are micro-organisms con- 
veyed through the blood. Thus in typhoid fever, tuberculosis, pneu- 
monia, and various forms of septicopyemia the specific organisms 
have been discovered in the areas of inflammation. Similar inflamma- 
tions occur in mumps, scarlet fever, and small-pox, and are doubtless 
caused in the same way, though the specific organisms are unknown. 
In these cases the testis is more frequently affected than the epididymis. 

In a third group of cases infection occurs through the vas deferens, 
and the epididymis is affected first and often alone. The most fre- 
quent infectious agent in this group of cases is the gonococcus; but 
other micro-organisms may enter the vas deferens, reach the epididymis 
and cause inflammation, in other diseases of the bladder or urethra, 
or after operations upon these parts, such as crushing vesical calculi, 
cutting urethral strictures, and the like. 

Pathological Anatomy. — Inflammations of the different parts 
may be separately considered. 



864 



A TEXT-BOOK OF PATHOLOGY 



In acute orchitis the testis is more or less edematous and swollen 
on account of inflammatory exudation. Microscopically, the strik- 
ing feature is round-cell infiltration of the intertubular tissues. This 
may be diffuse and uniform, or may occur in circumscribed areas, the 
latter being especially common in the orchitis of variola and pyemia. 
The round cells may infiltrate the walls of the tubules, and may be 
discharged into the tubules in great numbers. At the same time the 
epithelial cells may suffer degeneration and desquamation. Intense 
orchitis may lead to the formation of abscesses, single or multiple. 
These may subsequently undergo complete absorption, or may become 
inspissated and • encapsulated, the contents of such a focus consisting 
of fatty detritus and cholesterin. In other cases the abscess may 
rupture externally, and occasionally granulations springing from the 
tunica albuginea or the testis may protrude through the opening. The 
term benign fungus is applied to this condition. 

Chronic orchitis usually results from the acute form. The inflam- 
matory changes of the intertubular tissues gradually lead to indura- 
tion, and the testis becomes hard and contracted, the connective tissue 
and septa being increased in density, the tubules at the same time suffer- 
ing degeneration and atrophy. In cases following acute suppurative 
orchitis the tissues surrounding the inspissated abscess become sclerotic, 
and the tubules are in large part or wholly destroyed. Small nodular 
areas are discovered in such cases, and on section these are found to 
consist of a dense wall of fibrous tissue enclosing thickened pus contain- 
ing fatty detritus and cholesterin. The membranes surrounding the 
testis are usually thickened and united by adhesions. 

Chronic orchitis without a definite antecedent acute stage is a fre- 
quent result of syphilis (see page 867) . 

Acute epididymitis occurs when infective agents have reached the 
epididymis through the vas deferens. There is tense swelling of the 
epididymis, and not rarely associated inflammation with serous exuda- 
tion in the tunica vaginalis. The testis is not, as a rule, involved. 
The process begins as an acute catarrhal inflammation of . the tubules 
of the epididymis; later, cellular infiltration and occasionally abscess- 
formation occur in the intertubular connective tissues. The inflam- 
mation is sometimes completely resolved, but in other cases fibrous 
thickening, diffuse or nodular, results. Inspissated abscesses surrounded 
by fibrous tissue are sometimes seen, as in orchitis. The epithelium of 
the tubules embedded in the new-formed fibrous tissue may undergo 
a certain amount of proliferation, suggesting the appearance of adenoma 
or cancer. The vas deferens may be permanently obstructed, and the 
tubules on the proximal side and in the testis may undergo cystic dis- 
tention. Extensive epididymitis very commonly causes atrophy of the 
testis. 

Vaginitis testis and periorchitis are terms applied to inflammation 
of the tunica vaginalis testis. This condition is usually the result of 
orchitis or epididymitis, but may sometimes occur as a primary inflam- 
mation resulting from traumatism or other forms of irritation. 

The tunica vaginalis is a reflection of the peritoneum, and inflammatory 
conditions arising in it resemble those of the abdominal peritoneum. 



DISEASES OF THE REPRODUCTIVE ORGANS 



865 



Serous or serofibrinous vaginitis testis is the most frequent form. 
This may be acute or chronic, and is characterized by the accumula- 
tion of small or large collections of serous liquid. In the acute form, 
leucocytes, fibrin, red blood cells, much albumen and a high specific 
gravity are found. The quantity is usually less than in the slowly pro- 
gressive form. Anatomically one finds a plastic inflammation which may 
cause adhesions of the layers of the tunica. Sometimes the liquid is 
milky or turbid, and contains fat-droplets and cholesterin crystals. 
A chylous variety occurs in tropical countries, and is probably caused 
by the Filaria sanguinis hominis. In the chronic variety the contents 
are usually clear, of pale amber color, with a specific gravity of 1022, con- 
taining albumen and fibrinogen but not fibrin ferment, so that spontaneous 
coagulation does not occur; cells are scarce and usually of endothe- 
lial nature. Occasionally broken red blood cells may be present or hemo- 
globin may tinge the fluid. The quantity varies from a few ounces to 
many quarts. Anatomically there is a diffuse thickening of the tunica 
with or without adhesions. Calcareous deposits may occur in the wall. 

Hydrocele is the term used to designate effusions of these sorts. 
Sometimes the liquid contains spermatozoa, when the term hydrocele 
spermatica is applied. This condition is due to the escape of spermato- 
zoa from improperly developed spermatic tubules or from ruptured 
cysts of the epididymis or testis. In certain cases it is difficult to dis- 
tinguish hydrocele spermatica and spermatocele (see page 868). 

When hydrocele persists the tunica vaginalis undergoes hyperplastic 
thickening, and small, wart-like elevations may be formed (periorchitis 
prolifera). These nodules may become separated and remain in the 
sac as free bodies, like those in the joints. Another result of the second- 
ary inflammatory changes in the membrane is adhesion of the reflex- 
ions, causing a bilocular or multilocular hydrocele. 

When the canal connecting the sac with the peritoneal cavity has 
remained patulous the fluid of hydrocele may be pressed into the ab- 
dominal cavity. The term hydrocele processus vaginalis is applied to 
such cases, and the term hydrocele funiculi spermatid to cases in which 
only the upper part of the vaginal canal is patulous and filled with 
liquid. Hydrocele funiculi cystica results from collections of fluid in 
the middle portion of the canal, the upper and lower ends being 
obliterated. 

Purulent vaginitis testis occurs in association with epididymitis and 
orchitis, and sometimes primarily after traumatism. An ordinary 
hydrocele may be converted into a purulent collection by puncture with 
infected instruments. The sac is more or less distended with purulent 
liquid, and the surface of the membrane is covered with fibrinopurulent 
exudate. The pus may discharge externally, or may become inspis- 
sated; and extensive adhesions may obliterate the sac. 

Hemorrhagic Vaginitis Testis. — In severe acute inflammations the 
exudation may be more or less hemorrhagic. More distinctly hemor- 
rhagic forms of inflammation result from traumatism; in these cases 
there is first extravasation of blood and then inflammation. The sac 
may be fined with fibrinous and hemorrhagic deposits while the mem- 
brane itself is infiltrated and opaque. In the terminal stages consider- 

55 



866 



A TEXT-BOOK OF PATHOLOGY 



able thickening and sometimes calcification of the tunica vaginalis are 
observed. 

Inflammation of the vas deferens may be associated with epi- 
didymitis or orchitis, or may occur independently in cases of direct 
traumatism. In syphilitic disease of the testis, and less commonly in 
other forms of orchitis, the vas deferens may be greatly thickened. 

Varicocele is a tumor made up of dilated vessels of the pampiniform 
plexus and spermatic veins. It is due to obstruction sometimes with 
thrombosis of the venous flow by foreign masses, or the cases arising 
without such reason are ascribed to the weight of the blood column upon 
vessels with poor walls and valves. It is commonest in the young, and 
appears most often on the left side. The left spermatic vein empties 
at right angles into the renal vein, so that there is in this vessel a long 
column of blood in an almost directly vertical position. By some, 
varicocele is looked upon as due to congenital malformations of veins 
since testicular atrophy so often occurs concomitantly, and other vari- 
cosities may be found in the same case. 

INFECTIOUS DISEASES 

Tuberculosis is most frequent in the epididymis, but may involve 
the testicle as well. The infection occurs in one of two ways: either 

through the vas deferens, in consequence 
of tuberculosis of the prostate, seminal 
vesicles, or bladder; or through the cir- 
culation in cases of pulmonary or other 
forms of tuberculosis. It has been shown 
that tubercle bacilli are discharged from 
the body in the seminal fluid in cases of 
pulmonary and other forms of tuberculosis; 
and when local conditions predispose 
tuberculous infection of the epididymis 
may occur. Gonorrheal epididymitis seems 
to constitute such a local predisposition. 
Primary hematogenous infection of the 
epididymis seems to occur in rare cases. 

In cases of infection through the vas 
deferens there are formed in the walls of the 
tubule of the epididymis small tuberculous 
masses, which rapidly increase in size and 
run together, forming caseous areas of con- 
siderable size. Further invasion occurs 
along the lymphatic channels and the 
tubules, and rapid involvement of a considerable part of the epididymis 
results (Fig. 433). The tubule surrounded by tuberculous tissue may 
become filled with desquamated epithelium and puriform or caseous 
matter, and may be dilated in a cystic form. Extension to the testicle 
may occur, but is unusual, although having occurred, the specific lesions 
follow the type given for the epididymis. In addition, peritubular cell 
increase and epithelial degeneration seem to take place all over the 
organ, even at places where no actual tuberculous milia or granulation 




Fig. 433. — Tuberculosis of the 
epididymis and testicle (modified 
from Bollinger). 



DISEASES OF THE REPRODUCTIVE ORGANS 



867 



tissue develops. In long-standing or inactive cases indurative orchitis 
supervenes. 

Associated serous or serofibrinous vaginitis testis is not infrequent; 
and in some cases the tuberculous disease itself extends to the testicular 
envelopes and causes nodular elevations, or ulcerations and fistulous 
communications with the surface. 

Hematogenous tuberculosis of the epididymis is, in the first place, 
of the miliary form, but the tubercles grow rapidly and caseous nodules 
are rapidly formed. 

Tuberculosis of the vas deferens may be secondary to tuberculosis 
of the seminal vesicles and bladder, or of the epididymis. It is charac- 
terized by caseous swelling of the walls of the duct. 

Syphilis is not infrequently seen in the testicle in the late stages 
of acquired syphilis and in congenital syphilis. The epididymis and 
the membranes are secondarily involved. Two forms may be dis- 
tinguished. The more frequent is that in which diffuse induration of 
the testicle occurs; in the less frequent variety there are circumscribed 
gummata. In the diffuse form the organ is more or less uniformly 
indurated, and on section dense bands of fibrous tissues are conspicuous. 
The tubules suffer compression, degeneration, and atrophy, and some- 
times become converted into cheesy foci which can only be surely dis- 
tinguished from tubercles by finding specific organisms. The gummata 
have the usual translucent or cheesy appearance. When the membranes 
are involved diffuse thickening occurs; and in rare cases the disease 
extends to the skin, causing superficial granulations (syphilitic fungus). 
The vas deferens is often greatly thickened, as are also the walls of the 
blood-vessels of the testis and epididymis. 

Lepra of the testis occasions nodular lesions and pressure-atrophy 
of the tubules. Lepra-cells containing bacilli, as well as free bacilli, 
occur in the tubules in abundance. This fact is important as indicating 
a possible mode of transmission of the disease. 

TUMORS 

New growths of the testis are not very common and are seldom 
pure in type, being nearly always of the mixed or teratomatous varieties. 
This has caused many classifications, none of which is satisfactory 
so that the order given below represents the predominating character 
or cell type. Pure fibroma is said to occur but is extremely rare. Mixed 
tumors consist of all tissues entering into the physical make-up of the 
body, cartilage, connective tissue and glandular elements being most 
prominent. Muscle tissue, either striated or plain, enters into the 
mixture or may at times be almost pure. Chondroma may be said to be 
never pure. Connective tissue activity is shown in : 

Sarcoma, which may occur in any of its various forms in the testis, and 
less commonly in the epididymis. The supporting tissue between the 
tubules is its usual starting place, but the "interstitial cells" are believed 
by some to be capable of sarcomatous growth. Sarcoma forms rapidly 
growing whitish or reddish tumors. Secondary changes, such as fatty 
degeneration, hemorrhage, cystic softening, and caseation, are not infre- 
quent. 



868 



A TEXT-BOOK OF PATHOLOGY 



Carcinoma is the name applied usually to the hyperplasias of gland 
cells, which, though of mesodermic origin, behave somewhat like epithe- 
lium. There is a distinct tendency to cystic adenomatous change but 
medullary or scirrhus forms are known; all of them tend to show myxoid 
and colloid degenerations. More or less complete destruction of the 
testicle arid epididymis is frequent, but the tunica albuginea usually 
resists invasion for a considerable time (Fig. 434). Combinations of 
glandular and connective tissues have been termed adenosarcoma, in 
which the latter element is represented characteristically by large vacuo- 
lated cells with vesicular nuclei. 
Metastasis through the lymphatics 
and blood-vessels is frequent, and 
extension through the testicular 
envelopes to the skin may occur; 
spread may follow the vas deferens 
to the retroperitoneal tissues. 
Some tumors of the testicle show 
hyperplasias about the lymphatics 
and blood vessels which seem to 
deserve the name endotheliomata 
but because they tend to grow 
into alveolar form, they have also . 
been grouped among the sarcomata. 
Whatever they may be, they are 
exceedingly malignant. 

Chorioepithelioma is not in- 
frequent in the testis and is looked 
upon by many as supporting the 
theory that mixed growths of the 
organ are the result of the presence 
of some fertilized germ cells which 
attempt to produce a fetus in fetu 
and to form a tissue like the 
placenta. 

Cysts. — Retention-cysts of the tubules are frequent in cases of in- 
flammation and induration of the testis and epididymis. Sometimes 
they contain a simple milky liquid; in other cases spermatozoa are 
found in the fluid, and to these cysts the term spermatocele is applied. 
The cysts may be numerous and small, or may be very large, containing 
a hundred or more cubic centimeters of liquid. The cysts are found in 
the body of the organ; but, when large, project from the surface. Very 
large cysts push the testicle and epididymis to one side. Occasionally, 
cysts originate from the hydatids or the paradidymis. These may be 
spermatoceles, when one of the vasa aberrantia opens into them. 

Secondary proliferations of the epithelium of the cysts may convert 
a simple into a papuliferous cystoma; and occasionally the primary 
process seems to be one of adenomatous character, the cystic condition 
being the result of secondary distention or of the peculiar character of 
the acini formed. 




Fig. 434. — Carcinoma of the testicle 
(from a specimen in the Museum of the 
Philadelphia Hospital). 



DISEASES OF THE REPRODUCTIVE ORGANS 



869 



Small cystic cavities may contain mucous liquid or thick, curdy 
material. In the latter case the term atheromatous cyst is applicable. 

Dermoid cysts are occasional tumors of the testis proper. They 
may be simple sacs, lined with epidermal tissue and filled with pulta- 
ceous matter; or complicated dermoids, containing teeth, bone, muscle- 
fibers, and nerve tissue. 

PARASITES 

Echinococcus cysts are encountered on rare occasions. 

The Prostate Gland 
inflammation 

Inflammation of the prostate, or prostatitis, is most frequently 
secondary to posterior urethritis. Sometimes, however, it occurs in 
other ways, such as metastatic involvement in general pyemia or other 
forms of infection. Inflammations in the vicinity, such as cystitis, 
periproctitis, or vesical calculus, the passage of unclean instruments and 
direct injuries of the prostate may likewise cause acute inflammation. 

Pathological Anatomy. — A simple and a suppurative form may be 
distinguished. 

Simple Prostatitis. — In the ordinary prostatitis following urethritis 
the disease takes the simple form, the gland being congested and swollen 
and causing by its enlargement more or less obstruction of the urethra. 
Small suppurative foci may be formed in and about the glandular pouches 
and tubules. Catarrhal changes are seen in the tubular mucosa. 

Suppurative or phlegmonous prostatitis, or abscess of the prostate, 
may be a terminal condition of the previous form, or it may be developed 
primarily. In cases of metastatic prostatitis a number of foci of sup- 
puration may occur and subsequently coalesce, or a diffuse suppurative 
infiltration may take place. The development of abscesses is usually 
acute, though in some cases it may occur insidiously. If the abscesses 
are small they may subsequently undergo encapsulation, inspissation, 
and even calcification. Larger abscesses are prone to rupture into the 
urethra, usually through a number of openings. Sometimes, however, 
the inflammation extends to the tissues around the gland, causing peri- 
prostatitis, and later rupture into the rectum may occur. Extensive 
phlegmonous inflammation of the pelvic tissues is an unusual result. 

Chronic prostatitis is usually a companion of long-standing gonorrhea, 
and may assume a catarrhal or interstitial form. The catarrhal is more 
common, but there is always some indurative change. There is a thick, 
mucopurulent secretion in the tubules, which may dilate or coalesce 
by degenerative softening of the interstitial tissue. 

ATROPHY AND DEGENERATION 

Atrophy of the gland is occasionally met with in youthful indi- 
viduals, and may be the result of arrested development or disease of the 
testis. Excision of the adult testis for hypertrophy does not result in a 
reduction of the glandular and connective tissue and thus to atrophy but 
only to a reduction of congestion. It also occurs in the aged, and in 



870 



A TEXT-BOOK OF PATHOLOGY 



this case atrophy of the tissues surrounding the prostatic ducts may be 
accompanied by dilatation of the ducts themselves, the gland then pre- 
senting a cavernous appearance. Atrophy of the gland sometimes leads 
to incontinence of urine. 

Fatty degeneration of the epithelium of the gland and of the 
muscle-fibers is frequent in old age, and may occur as an independent 
condition or in association with hypertrophic enlargement of the gland. 
The gland becomes soft and diffusely yellow or mottled in color. 

CONCRETIONS 

Prostatic concretions are not unusual in persons of advanced age, 
and are frequently found in considerable numbers. They vary in size 
from almost microscopical granules to bodies the size of a millet-seed. 
They may be colorless at first, but usually become brownish. On sec- 
tion through the gland these brownish-colored bodies give the appear- 
ance of a surface sprinkled with snuff. The granules are usually round 
or oval, and are characterized by concentric lamellations. The term 
amylaceous bodies has been applied to them, and they have been sup- 
posed, though erroneously, to be composed of amyloid material, such as 
occurs in amyloid degeneration. Sometimes they reach considerable size, 
when calcareous salts deposit around them and give them an irregular 
form. Sometimes the concretions are discharged through the prostatic 
ducts into the urethra; in other cases. the larger concretions project 
prominently into the urethra beneath its mucous membrane. 

INFECTIOUS DISEASES 

Tuberculosis of the prostate is usually found in association with 
tuberculosis of the other genital organs, especially the vas deferens and 
epididymis. It is also met with in association with tuberculosis of the 
bladder or kidney. The prostate is usually diffusely enlarged, and may 
be somewhat nodular upon the surface. On section caseous areas are 
found, or the entire gland has a caseous appearance. Recent tubercles 
are rarely visible, as caseation progresses with unusual rapidity in this 
organ. The process tends to empty itself into the urethra, either by the 
natural course or through ulcerative openings, and to penetrate the 
capsule to the periproctal tissue whence it may ulcerate into the rectum. 
Primary tuberculosis of the prostate is rare. 

HYPERTROPHY AND TUMORS 

Hypertrophy of the prostate is a condition of clinical and patho- 
logical importance because of its common appearance after the age of 
fifty, the frequency of consequent cystitis and ascending infections, and 
the invalidism it occasions. Practically all. hypertrophies of the pros- 
tate will fall into two divisions: first, those due to inflammatory dis- 
ease, either primary or by obstruction and extension from the urethral 
outlets of the gland, and, second, those due to a more or less distinct 
tumor growth of some of the constituent tissues of the organ. In some 
cases chronic posterior urethritis seems to be the important factor; in 
other instances disturbances of the circulation, and especially varicose 
conditions of the veins, are active in the causation. 



DISEASES OF THE REPRODUCTIVE ORGANS 



871 



The organ may enlarge in a uniform manner, or there may be nodular 
or localized swelling. Of the localized form the most important, from a 
clinical aspect, is that in which the middle lobe or the isthmus of the 
gland enlarges and projects under the posterior wall of the urethra as a 
small or large rounded elevation, or as a transverse bar or obstruction 
(Fig. 435). According to the investigations of some authorities, the 
enlargement in such instances is due to a hyperplasia of accessory pros- 




Fig. 435. — Hypertrophy of the prostate. Seen from within bladder. 



tatic tissue lying immediately under the mucous membrane of the 
bladder and of the prostatic portion of the urethra, with subsequent 
involvement of the isthmus of the gland itself. 

On section through the gland there may be a uniform induration, 
or in other cases, in consequence of associated changes in the epithelium 
or acini, there may be scattered through the gland areas of softening or 
of proliferation of the glandular elements, or cystic distentions of the 
gland tubules. In such instances the indurated gland presents more or 
less softened or cystic foci. 

Microscopically, in the diffuse form, involving the stroma alone, 
the gland presents merely the features of uniform fibromyomatous 
proliferation, and corresponds in structure with fibromatous or myo- 



872 



A TEXT-BOOK OF PATHOLOGY 





Fig. 437. — Detail of the fibroma- and adenoma-like hypertrophy of the prostate gland. 
Glands are distorted, sometimes hyperplastic, sometimes containing amylaceous bodies. 

tinctly adenomatous character is added. There is usually some inter- 
stitial round-cell increase, a condition suggesting that inflammatory 
lesions are associated, whether or not they are primary. The glandular 



DISEASES OF THE EEPRODUCTIVE ORGANS 



873 



elements may undergo fatty degeneration, and the lumina of the acini 
and tubules may be filled with milk-like, fatty material. In other cases 
pronounced cystic distention of the gland occurs. 

Results of Hypertrophy of the Prostate. — Enlargements of the 
prostate usually interfere with the discharge of urine. This is particu- 
larly marked in cases in which the middle lobe projects into the urethra, 
though in some instances the opposite result may be produced, viz., 
incontinence of urine due to interference with the contractions of the 
sphincter of the neck of the bladder. In cases of enlargement of one of 
the lateral lobes obstruction to the flow of urine is caused by lateral 
deviation and compression of the urethra. Upward and forward pro- 
jection of the middle lobe forms a reservoir in the postero-inferior part 
of the bladder, where fermentation and infective cystitis may begin. 

The muscular walls of the bladder at first become hypertrophied, 
but dilatation of the bladder subsequently occurs. Cystitis, distention 
of the ureters and renal pelves, and ascending infection, causing ureteri- 
tis, pyelitis, and pyelonephritis, are among the late results. 

Sarcoma is a rare tumor of the prostate. It generally has the char- 
acters of lymphosarcoma, and is a rapidly growing, destructive tumor. 
In some cases combination with adenoma has been observed. Sarcoma 
is, indeed, rarely pure in type, rhabdo-myomatous elements being com- 
monly present. This tumor is commonest in childhood. 

Carcinoma of the prostate is more frequent than sarcoma, though 
it is not a common tumor. The tumor arises from the epithelium of the 
tubules, and takes the form of nodular, grayish or white masses which 
cause irregular enlargements of the gland, and not rarely project into 
the urethra or the base of the bladder. The cells of prostate cancers 
are quite small and stain rather deeply, giving an impression of sarcoma 
cells. Superficial ulceration of the mucous membrane over these pro- 
jections is not infrequent. The stroma of the gland usually proliferates 
actively. Metastasis to the inguinal glands, or to distant parts, espe- 
cially the bones, is not infrequent; but direct extension to the bladder, 
seminal vesicles, or rectum is more common. There may be frank 
adenomata of the prostate; these are usually associated with or the cause 
of "hypertrophy." 

Cysts of the prostate are usually the result of retention of exudates 
within the glands or their ducts. Occasionally, cystic formations seem 
to arise from remnants of Miiller's ducts. 



Cowper's Glands 

Inflammatory conditions are met with in these glands in association 
with similar affections of the prostate. Occasionally, independent in- 
flammation of Cowper's glands results from posterior urethritis. The 
gland is enlarged and presents the usual appearances of inflammation. 
The termination may be abscess-formation. Obliteration of the mouths 
of the ducts may occasion cystic conditions in the glands, and carcinoma 
has been described. 



874 



A TEXT-BOOK OF PATHOLOGY 



The Seminal Vesicles 

Inflammation. — Acute inflammation of the seminal vesicles may 
occur in association with gonorrheal urethritis. The vesicles become 
distended with seminal secretion and mucopurulent exudate. Their 
walls are swollen, and the mucous membrane presents the appearance 
of catarrhal inflammation. 

Chronic inflammation may result from the acute form; it causes con- 
traction and thickening of the walls. 

Tuberculosis of the seminal vesicle is common in cases of uro- 
genital tuberculosis. The vesicles are rarely independently affected. 
The walls become thickened and may present nodular, cheesy masses, 
and there may be ulcerations of the mucous surface. The cavities of 
the vesicles contain caseous or puriform material. 

Tumors. — Primary carcinoma has been described; but secondary 
carcinoma, resulting from extension of cancer of the adjacent structures, 
is more common. 

Cystic distention and the formation of diverticula result from obstruc- 
tions of the ejaculatory duct. The contents of the vesicles in such cases 
are seromucous in character. 

Concretions frequently result from calcification of inflammatory 
exudates. They are especially frequent in association with tuberculosis. 

The Mammary Glands 

congenital abnormalities 

Absence of one or both breasts may occur in association with other 
defects of development of the thoracic walls. Incomplete development 
of the mammary glands, or hypoplasia, may be associated with hypo- 
plasia of the genital organs. The gland may be complete but the duct 
and nipple may be absent, athelia. 

Supernumerary mammary glands are frequently observed; 
the term polymastia is given this condition. The supernumerary gland 
or glands may be situated between the normal glands, below these, or 
in distant parts, such as the back, shoulders, and arms. They may occur 
in either sex, and may be structurally complete and functionally active; 
or may be merely rounded masses of mammary tissue without excretory 
ducts or nipples. In the latter instances the probable explanation of the 
condition is that in the process of development parts of the normal glands 
have been split off and have separately developed. 

Early Development. — The mammary glands may be developed 
at an abnormally early period, in association with early development of 
the genital organs. 

Abnormal functional activity (secretion) may be stimulated by 
various diseases of the genital organs; and in the newborn of either sex 
during the first week of life slight secretion of colostrum-like material is 
frequent. 

Abnormal development of the male breast is occasionally 
observed, especially about the age of puberty, and sometimes copious 



DISEASES OF THE REPRODUCTIVE ORGANS 



875 



secretion of milk takes place. Usually the organ subsequently atrophies, 
but exceptionally the enlargement and secretion persist. 

CIRCULATORY DISTURBANCES 

Hyperemia occurs during the menstrual period and at the beginning 
of lactation, as a physiological process, and causes slight swelling and 
redness. Pathological hyperemia plays a part in the process of inflam- 
mation. 

Hemorrhages are usually the result of traumatism. They may 
occur into the gland itself, or into the connective tissue in front of or 
behind the gland. Occasionally, hemorrhages are due to intense inflam- 
tion or to tumor-formation, especially from intracanalicular papilloma, 
epithelioma or cystadenoma. The blood may find its way into the 
lactiferous tubules, and may be in part discharged from the nipple. 
In case of large hemorrhages the blood may subsequently undergo 
absorption or inspissation, and hemorrhagic cysts may be formed. 
Occasionally, hemorrhage occurs in the mamma and from the nipple at 
the time of the menses, as a form of vicarious menstruation or in cases of 
dysmenorrhea. 

INFLAMMATIONS 

Acute inflammation of the mammae, or acute mastitis, is 

rarely met with, excepting during the puerperium. Exceptionally it 
may occur in cases of general pyemia, or in the newborn as a result 
of active secretion and obstruction to the outlets. Sometimes inflam- 
mation of the glands results from direct extension of inflammatory 
processes of the skin, subcutaneous tissue, or thoracic walls. Puer- 
peral mastitis is infective in character, and results from injury or disease 
of the nipple, through which the infective agents enter the glands. The 
actual portal of entrance may be the discharging tubules, or fissures 
and erosions of the nipple. Hematogenous mastitis is also recognized 
as an occasional complication in puerperal sepsis and in the acute in- 
fectious diseases like scarlatina, parotitis and typhoid fever. Various 
micro-organisms have been discovered, including staphylococci and strep- 
tococci, of which the latter is the more common in the puerperium. 

Thelitis, inflammation of the nipple, is common in nursing women 
when they are at all uncleanly, since the act of sucking favors the pro- 
duction of small wounds. The inflammation of the mamma following 
thelitis is usually catarrhal, but may be interstitial. 

Pathological Anatomy.- — The gland is swollen and distends its cap- 
sule tensely, the skin is reddened, and a general hyperemia of the gland 
is noted. During the earlier stages the inflammation may be localized 
or may be diffuse. In the former case more or less circumscribed indura- 
tion is discovered, while in the latter the organ is uniformly indurated. 
The tendency of mastitis is to terminate in suppuration. On section 
through the gland, areas of light-yellowish color indicate the purulent 
infiltration, while in the later stages more or less extensive abscesses are 
formed. The latter may communicate with the lactiferous tubules 
and pus and milk may be discharged from the nipple. The abscesses 
tend to extend in various directions, and may finally rupture upon the 



876 



A TEXT-BOOK OF PATHOLOGY 



surface through fistulse. After discharge of the pus granulation tissue 
is formed, and the cavities are obliterated by cicatricial tissue. When the 
larger discharging tubules are opened by the abscesses fistulse may be 
formed, which continuously discharge milk. Small collections of pus 
may become encapsulated and inspissated, being converted into cheesy 
partly calcified matter. 

The connective tissues around the mammary gland are sometimes 
involved hy extension, and suppurative or necrotizing perimastitis, or 
retromammary abscess, results. Extension to the thoracic walls and 
pleura is rare. 

Chronic mastitis may be divided into the diffuse fibrous thicken- 
ing leading to atrophy and the irregular or nodular type resembling 
cystic adenoma. It cannot be said that there is any sharp separation of 
the two groups or that an etiological difference exists since all sorts of 
gradation occur. The first variety is represented by normal involution 
after the menopause and by low grade peritubular fibrosis with epithelial 
atrophy. The cystic variety in its most decided form is the continuing 
activity of fibroblasts with irregular involvement of glands and ducts 
whereby some are compressed or occluded, the less constricted lumina 
underoging dilatation. In the simple atrophic type, fibrous or even 
fibromatoid pictures are obtained ; dense, glistening, pale, irregular strands 
sweep across a cut surface of the breast, under the microscope showing 
themselves as relatively cellular bands surrounding compact non- 
functionating gland groups. In the cystic form on the other hand, 
strands of fibrous tissue may separate fatty or glandular areas or may be 
the septa of definite cystic cavities ; the latter contain a turbid fluid like 
milk, or inspissated material. Under magnification one sees in such a 
breast irregularities in size and shape of the acini and ducts while the 
epithelium tends to become low or even flat. The interstitial tissues are 
nearly always well seeded with mononuclears — plasma cells and lympho- 
cytes — while mast cells and giant cells are at times encountered. It is 
frequently difficult to decide whether one deals with a chronic mastitis 
in the one hand or fibroma or adenoma in the other. The simple variety 
gives a small hard gland, the cystic, a nodular, uneven irregular organ. 

ATROPHY AND HYPERTROPHY 

Atrophy of the gland occurs as a physiological process after the 
menopause, or it may result from local causes, such as abscess or tumor- 
formation. Artificial menopause, following oophorectomy or diseases 
of the reproductive organs, may occasion atrophy similar to that nor- 
mally present in old age. The gland may simply decrease in size, without 
notable change of any other kind. Sometimes, however, connective- 
tissue hj'perplasia accompanies the atrophy of the glandular elements, 
and diffuse infiltration may occur. 

Hypertrophy of the gland is sometimes met with in girls at the 
age of puberty, and leads to a uniform enlargement of the organ. In 
some cases there is a true hypertrophy of all the constituents of the 
gland; in other instances dilatation of the lymphatic channels, or de- 
generative changes, may cause a simulation of true hypertrophy. Both 
breasts, as a rule, are affected, and there may be increased functional 



DISEASES OF THE REPRODUCTIVE ORGANS 



877 



activity (galactorrhea). Vicarious hypertrophy of one breast may occur 
after loss of the other. Tumors of the uterus and ovaries are sometimes 
accompanied by enlargement of the breasts. 

DEGENERATIONS 

Fatty infiltration, or lipomatosis, of the gland may accompany 
atrophy of the secreting tissue, or may occur as an independent con- 
dition. The gland may be greatly enlarged. Accompanying this 
infiltration there is usually diffuse hyperplasia of the connective tissues. 
Myxomatous degeneration may be associated with fatty infiltration. 

INFECTIOUS DISEASES 

Tuberculosis of the mammary gland as a primary lesion would be 
most easily accounted for by invasion through the nipple but could 
of course come via the blood stream. It is certainly extremely rare and 
its existence has been denied by some. Secondary tuberculosis arises 
by extension from the lymph nodes of the neck, axilla or anterior medias- 
tinum, from the ribs, or from the lungs. According to Deaver and 
jYIacFarland an antecedent mastitis is not at all necessary for its 
development. The disease assumes various forms: Single nodular 
mastitis presents an illy outlined firm or caseous interstitial and glandular 
mass of inactive character while the disseminated nodular variety 
is more progressive, with a tendency to perforate the skin to form 
fistula?; certain of these cases are combined with fibrous tissue formation, 
the sclerosing form. Sluggish cases may be characterized by a diffuse 
overgrowth of connective tissue and atrophy of epithelium with oblitera- 
tion of the tubules, the obliterating type; the last is very rare. Occasion- 
ally tuberculosis and carcinoma are combined. It is difficult to find the 
bacilli in discharges or sections. 

Syphilis, in the form of gummata, is sometimes met with in acquired 
or congenital syphilis. Chancres or mucous patches may occur on the 
nipple. 

TUMORS 

Fibroma may be met with in the form of circumscribed nodular 
growths, or, according to the view of some pathologists, as a diffuse 
process. Circumscribed fibroma presents itself as a hard, nodular 
tumor, often having a distinct capsule, and on section presenting a 
lamellar arrangement. The glandular elements of the organ in the area 
of invasion may undergo secondary hyperplasia, and thus a form of 
fibro -adenoma may be developed. In the cases termed diffuse fibroma 
the entire organ may be indurated, or nodular areas of sclerosis may be 
found in various parts of the gland. The fibrous tissue may appear 
directly around and compress the glandular structure (pericanalicular 
fibroma), or the acini and ducts may at the same time undergo prolifera- 
tion forming adenomatous structures, the true fibro-adenoma, or compres- 
sion of the ducts may lead to retention cysts (cystadenofibroma) . It is 
difficult to determine in some cases whether the process is one of tumor- 
formation or one of inflammatory hyperplasia. 



878 



A TEXT-BOOK OF PATHOLOGY 



A form of particular interest is that known as intracanalicular 
fibroma. In this the proliferating fibrous tissue projects into the 
normal or dilated tubules in the form of papillary ingrowths. The 
mucosa lining the tubules is pushed forward by the ingrowths, and 
covers these in the same manner as epithelium covers superficial papil- 
lomata of the skin or mucous membranes. At times the epithelium 
proliferates extensively; this may be due to inflammation or to an adeno- 
matous change in the mucosa. The gland may be greatly enlarged, and 
on section presents an appearance resembling that of a cut through a 
cauliflower (Fig. 438). All the tumors just under discussion may undergo 
sarcomatous change but carcinoma rarely develops from them. 




Fig. 438. — Intracanalicular fibroma of the mammary gland (Kaufmann). 



Lipoma of the mammary glands occurs in the form of round, encapsu- 
lated tumors of the interstitial or periglandular connective tissues. They 
may be bilateral. 

Myxoma may occur in a diffuse form, causing a transformation 
of the gland into myxomatous material, or as circumscribed tumors. 
New growths of the fibroadenoma group are very prone to show this 
change sometimes in combination with sarcoma. 

Myomata containing smooth muscle-fibers, and mixed tumors 
containing striated muscle-fibers, are rare. 

Chondroma and osteoma have been observed. 

Sarcoma is most frequently of the round-cell variety but may be 
of any kind, including the melanotic and mixed forms. It occurs in a 
diffuse form or as circumscribed nodules, either one of which may attack 
the skin and protrude as a fungoid mass. 

In diffuse sarcoma the gland undergoes a uniform enlargement, 
and the neoplasm extends rapidly, forming attachments to the skin 
and sometimes causing superficial ulceration. In other cases extension 
toward the chest walls may occur, finally involving the pleura. On 



DISEASES OF THE REPRODUCTIVE ORGANS 



879 



section through the gland a lobular character of the tumor may be recog- 
nized, and areas of fibrous or myxomatous character are visible here 
and there. Cystic conditions, sometimes met with, may be due to 
obstruction and consequent distention of the lactiferous tubules. The 
term cystosarcoma is appropriately applied to such cases. The sarcoma- 
tous tissue may project into the dilated tubules in a polypoid form 
(intracanalicular sarcoma). Section through the gland in such cases 
presents an appearance not unlike the surface of section of a head of 
cabbage. Cysts may also be formed in sarcomata by degenerative 
softening. 

Localized sarcomata occur as smooth, firm, movable, nodular tumors 
arising from the connective tissue surrounding the acini. They push the 
secreting tissues ahead as they grow, causing atrophy of the gland. 
On section through the tumor the glandular acini may be seen within the 
nodules. Certain of the nodular sarcomata take a distinct alveolar 
form after the manner of endo- and peritheliomata and have been so 
denominated. 

In any form of sarcoma the epithelium of the tubules and acini 
may undergo secondary proliferation, when the term adenosarcoma is 
applicable. 




Fig. 439. — So-called chronic cystic mastitis. On the left dilated canals with peculiar 
epithelial overgrowth. On the right normal glandular acini (modified from Aschoff). 

Adenoma. — Most of the tumors of the mammary gland are asso- 
ciated with some change in the secreting tissue, and it is often difficult 
to estimate how large a part this plays in the new growth. Degeneration 
or hyperplasia of the epithelium and obstruction of the lumen are the 



880 



A TEXT-BOOK OF PATHOLOGY 



common alterations. Constriction of the ducts leads to cyst formation, 
and the process is little different when caused by chronic inflammation 
or neoplasms. In the tumors beginning as adenomata or with this type 
dominant, the acinous grouping is retained in those parts not becoming 
cystic, while in carcinoma any progressive change in the acini is atypical. 

Adenoma of the mammary glands may be an independent growth, 
or may be associated with fibroma, sarcoma, or other tumors. The 
independent form presents itself as a circumscribed, encapsulated, 
nodular tumor, somewhat firmer thaD the substance of the normal gland. 
Microscopically, adenoma follows the tubular or acinus architecture, there 
being increase of the ducts or secreting areas respectively. These are 
usually somewhat dilated, and the epithelial cells are larger than those of 
the normal gland (see Fig. 439). The lining cells may be reduplicated 
and somewhat irregular but there always is a well emphasized, even hya- 




Fig. 440. — Ulcerated carcinoma of the breast. 



line basement membrane for their support. Fatty degeneration of the 
cells is not infrequent, and sometimes there is a certain amount of milk- 
secretion, causing additional distention of the cavities. Great distention 
of tubules and acini produces cystadenoma, which, with papillary out- 
growths of the mucosa taking place within dilated ducts or acini, is called, 
papillary cystadenoma. This growth sometimes appears as an independ- 
ent condition at the menopause or at a younger age affecting both sides 
and is often termed cystic disease of the breast (see chronic mastitis). 
The organ is irregular, nodular, firm and cystic. Retraction of the nipple 
may occur, but metastasis does not. Histologically these tumors are 
benign, unless one can find distinct separate epithelial groups without a 
basement membrane. 

Carcinoma may develop from the tubules or from the acini of the 
glands. It may begin as an adenomatous tumor, which subsequently 



DISEASES OF THE KEPRODUCTTVE ORGANS 



881 



undergoes carcinomatous transformation, or may be a typical glandular 
cancer from the beginning. In the cases primarily adenomatous the 
structure of the acini becomes atypical and the epithelial cells tend to 
penetrate the membrana propria and form irregular collections or col- 
umns in the interstitial tissue. Degenerative changes are often ob- 
served, among which fatty degeneration is most frequent. Mucoid 
degeneration and a form of caseation are sometimes met with, and calci- 
fication may take place in the interstitial tissues. Occasionally an at- 
tempt at formation of milk occurs in the cancer-acini. 




Fig. 441. — Adenocarcinoma, mammary gland — tubular acinus portion — considerable 

fibrous tissue. 

Varieties. — Among the varieties of carcinoma are the squamous, 
medullary, the simple, the scirrhous, the myxomatous, and the so-called 
adenocarcinoma. 

The squamous carcinoma begins as an epithelioma of the nipple, or 
Paget's disease. The process proceeds by extension into the discharg- 
ing tubules and penetrates the gland structure. 

Medullary carcinoma, or soft cancer, is characterized by its softness 
and the abundance of liquid (cancer-juice). It grows rapidly and soon 
invades a large part of the gland, and attaches itself to the skin, which 
may finally be broken, exposing an ulcerated surface (Fig. 440). Actual 
inflammatory changes terminating in suppuration are not infrequent. 
The nipple is not retracted. 

56 



882 



A TEXT-BOOK OF PATHOLOGY 



Scirrhous cancer is slower in growth, and is usually very hard; the 
skin is firmly attached to the tumor, and the nipple is usually retracted. 
On section the tumor is found to be of a firm, fibrous, and somewhat 
translucent character; extensions of the growth are seen radiating in 
garious directions from the body of the tumor. Microscopically, the 
growth consists of fasciculated connective tissue, enclosing round or elon- 
gated collections of cancer-cells (see Fig. 98). 

Simple carcinoma stands between the medullary and the scirrhous 
forms in point of hardness, as well as in point of malignancy. The 
three forms differ only in the relative amount of epithelial elements and 
fibrous tissue. 

Myxomatous, colloid, or gelatinous cancer is a rare form in which 
the interstitial connective tissue suffers mucoid change, and the epi- 
thelial cells of the cancer-acini undergo more or less fatty or excep- 
tionally mucoid degeneration. 

Adenocarcinoma presents the general type of malignant adenoma. 
It may be solid or cystic or cystopapillomatous. It grows rapidly, and 
may go over into the soft or hard types. 

Malignant papillomata of the ducts have been seen. These may 
become extensive and carcinomatous. Hemorrhage into the ducts or 
through the nipple is common from them. 

Results. — Cancer of the breast may extend directly to the subcu- 
taneous tissues and skin on the one hand, causing an indurated growth 
(cancer en cuirasse), or to the walls of the chest and pleura on the other 
hand. Metastasis frequently takes place through the lymphatics, the 
axillary glands, as a rule, presenting the first evidence of the extension 
of the growth, but since there is a plentiful lymphatic drainage to the 
clavicular region, secondary nodules should be searched at this point also. 
Secondary growths are often found in the pleura and bones. Malig- 
nancy varies directly with the softness of the tumors, the scirrhous form 
frequently having a comparatively benign character. Sometimes the 
increasing growth of connective tissue in this variety leads to practical 
cessation of the growth of the tumor. 

Mammary cancers are much more frequent in the female than in 
the male sex. They are commonly met with after the age of forty, 
and traumatic influences seem to bear some relation to their occur- 
rence. 

Cysts. — Repeated reference has been made to the retention cysts 
of the lactiferous tubules caused by compression or other forms of ob- 
struction. The gland may present a few or many cystic cavities about 
the size of a pea, containing whitish or milky liquid. Occasionally 
the contents of the cysts are cheesy (atheromatous). Distention of the 
acini of the glands in consequence of obstructions to the outflow of milk 
may lead to large cystic tumors containing milk (galactocele) . In the 
later stages the contents of such cysts may become thickened or caseous. 



CHAPTER IX 



DISEASES OF THE BONES 

Anatomy and Development. — Bone is a dense form of connective 
tissue, the cement substance being impregnated with lime-salts. It 
may be spongy or compact in character. On transverse section one sees 
certain oval openings, surrounded by concentric lamellae of a substance 
containing lime-salts. Each opening is the end of a so-called Haversian 
canal, which with the surrounding lamella? form an Haversian system. 
The areas between the Haversian systems are filled with osseous tissue 
not arranged concentrically. Between the lamellae of bony tissue are 
seen irregularly oval spaces — lacunae — from which run branching canal- 
iculi. In preparations of fresh bone the lacunae are found to be occu- 
pied by the bone cells, which are irregular and have branching projec- 
tions extending some distance into the canaliculi. In the center of 
the bones are found hollow spaces containing the bone marrow. This 
is a vascular tissue, in the meshes of which are found large and small 
rounded cells resembling the lymphoid cells, red corpuscles, ordinary 
leukocytes, and some nucleated red corpuscles. A form of cell of particu- 
lar interest is the large multinucleated giant cell, or myelo plaque. The 
marrow extends in the form of projections into the substance of the 
bone and communicates with the Haversian canals. 

Surrounding the bone is the fibrous periosteum. This consists of a 
dense outer layer and a more cellular inner one, which is osteogenetic in 
function. 

Development. — The beginning of the change of the original cartilage 
into bone consists in the multiplication of the cartilage cells and their 
arrangement in longitudinal rows. They grow into cartilage corpuscles 
of considerable size, calcification at the same time occurring in the 
matrix between these cells. Simultaneously, vascular projections ex- 
tend inward from the perichondrium ; the cartilage cells and preliminary 
calcareous deposit are subsequently removed, primary marrow-spaces 
being thus formed. Bone-cells are deposited in the spaces between the 
original cartilaginous trabeculae, and at once begin to cover themselves 
with bony deposits, the cartilaginous trabeculae gradually diminishing 
by absorption. By these processes a spongy form of bone is developed. 
Subsequently the concentric calcareous lamellae of the Haversian sys- 
tems are deposited within the spaces, and the spongy bone is thus con- 
verted into the dense form. 

Disorders of Development 

Many congenital defects of development are observed, such as the 
appearance of supernumerary bones, the absence of certain bones, 
the failure of union between epiphyses and diaphyses, etc. Failure of the 

883 



884 



A TEXT-BOOK OF PATHOLOGY 



skeleton to assume its normal size, dwrafism, may be proportionate or 
irregular. The latter is shown in cretinism or associated with certain 
abnormalities of development in the skull, while the former, a rare occur- 
rence, seems to be simply a failure of normal growth, due in some cases 
apparently to too rapid completion of ossification, in others to 
incomplete use of skeletal areas already laid down. One condition of 
considerable interest (rachischisis) is considered on page 983. 
The most important developmental disease is rickets. 
Chondrodystrophia fetalis, or achondroplasia, is, as its name 
indicates, a congenital hypoplasia of the skeleton notably the long bones, 
giving rise to short legged, big-headed dwarfs with 
a well developed, even strong musculature. The 
extremities are short and thick, the ends of the 
bones enlarged, and the shafts bent. The hand is 
curiously like a trident by reason of wide separation 
of the second and third fingers. There is increase 
of the original cartilage and of the periosteum, 
with an arrest of development of the diaphyses. 
Subperiosteal bone formation is about normal, but 
epiphyseal growth is imperfect and the bones do 
not develop to their normal length. The most 
noteworthy pathological anatomy is the absence 
of adequate capillary supply to the osteogenetic 
layer of the epiphysis. The cause is obscure, but 
the condition seems hereditary. The disease is 
essentially one of disproportionate or irregular 
ossification of already mapped out cartilaginous 
parts in which the action of osteoblasts and osteo- 
clasts is "undisciplined " leading in place to 
softening in others to excessive bone deposit, result- 
ing in bones of irregular width. There is early 
fusion of the bones at the base of the skull but nor- 
mal growth of the vault, a condition said to cause 
a sinking in of the bridge of .the nose. It begins 
early in fetal life, probably in the second month. 
The thyroid shows overgrowth of alveolar epi- 
thelium and connective tissue, the former sur- 
rounding the latter, with the formation of separated islands of acini. 

Closely related to the above is osteogenesis imperfecta, which, as its 
name implies, is an ossification short of completeness. The charac- 
teristic is to be found in the skull, where only small plates of bone are 
laid down, and these fail to unite to form the large flat bones. This 
may be a congenital condition and children are sometimes born with 
fractures that occurred in utero. It probably is due to delayed action 
of the periosteum, so that the shafts of long bones are imperfect and 
multiple fractures are common, although osteoblastic activity seems 
normal up to the point of depositing sufficient bone salts. Fragillitas 
ossium, or generalization of this, is discussed on page 985. 

The effect of all these malformations is to render adjacent parts 
liable to damage and to favor fracture of the bones themselves. 




Fig. 442. — Chondro- 
dystrophy in a 12 year 
old girl (from the Vienna 
General Hospital Col- 
lection) . 



DISEASES OF THE BONES 



885 



RICKETS 

Definition. — Rickets, or rachitis, is a constitutional disorder, at- 
tended with abnormal developmental processes in the bones, of which 
active proliferation of the cellular elements and lack of normal calcifica- 
tion are the most important. 

Etiology. — The causes of rickets are still very obscure. The dis- 
ease is in some way connected with improper nourishment, though 
there is probably also an inherited disposition, or a constitutional con- 
dition expressing itself chiefly in an inability of the primary cartilage 
to absorb calcium salts and ossify normally. It has been sought to 
establish a connection between rickets and syphilis, but any such rela- 
tion is doubtful. Various chemical theories have been offered in ex- 
planation, a very ably defended one being that in some way calcium 
is eliminated in excess instead of being absorbed; the normal or very 
slightly reduced alkalinity of the blood in rickets speaks rather against 
this assumption. Formerly, it was supposed that the presence in the 
digestive tract of lactic acid in excess prevented the proper absorption 
of calcium; this theory, however, is generally abandoned. It does not 
seem that reduced calcium intake causes the disease, because experi- 
ments with low calcium diet do not produce rickets in young animals. 
Ribbert now asserts that the cause is toxic, the poison producing degen- 
erations in the cartilage-cells. Whatever the last analysis will show as to 
the cause, the absence of a well balanced diet for the child must still be 
looked upon as a potent factor. The disease occurs in infants during the 
first year of life, and continues during the second and third years, after 
which the active manifestations subside. 




Fig. 443. — Rachitic enlargement of the end of a rib (modified from Bollinger). 

Pathological Anatomy. — Rickets leads to various deformities, 
principally situated in the long bones and skull. The epiphyses, as 
those of the wrist, ankle, etc., are swollen, and in more advanced stages 
the shafts of the long bones may be variously distorted. 

Sharp bends {infractions) may be observed in the long bones, and 
complete fractures may occur. The alteration of the skull is charac- 
teristic. The head is large and square in shape, the forehead prominent, 
and the fontanels remain open a long time. Osteophytes may form, 
and not rarely areas are found in the temporal or other bones in which 
the mineral substance is deficient or almost completely wanting {cranio- 
tabes), the spaces being filled by a parchment-like membrane. Deformi- 
ties of the chest are frequent, the chicken-breasted condition being the 
most marked. In the beginning of the disease slight enlargement of the 
ends of the ribs at the junction with the costal cartilages, causing the 
beaded appearance called the " rachitic rosary," is observed (Fig. 443). 
Various distortions of the spinal column, flattening of the pelvis, and 
other deformities may be met with in marked cases. 



886 



A TEXT-BOOK OF PATHOLOGY 



The minute changes of rickets consist in a form of abnormal develop- 
ment, in which calcareous deposition does not progress in the normal 
manner, but is replaced by osteoid tissue and a proliferation of the 
cellular elements. In consequence of this the bone presents irregular 
areas of partial calcification lying between portions made up of greatly 
proliferated and enlarged cartilage cells. Between the epiphysis and 
diaphysis of long bones there is a wide irregular bluish zone of imper- 
fectly ossifying cartilage richly supplied with blood-vessels. Projections 
from the marrow and periosteum extend deeply and visibly into the body 
of the bone, which is thus composed for the most part of osteoid instead of 
osseous tissue. The marrow-spaces are irregular and excessive in size. 
These changes in the bone are marked at the epiphyseal extremities, and 
thus lead to the visible enlargements. It is thus seen that the process in 
rickets is failure of development of the normal structure, rather than 
absorption of existing bone although it is quite possible that absorp- 
tion of already deposited and fairly well organized osseous tissue may 
occur. The original calcareous deposit around the cartilage cells is 
largely or completely absorbed, as in normal bone-formation, and often 
even more rapidly. The subsequent deposit of calcareous bone does not 
form, but in place of it there occurs a rapid proliferation of cartilaginous 
and other cells. It is perhaps well to emphasize that both osteogenetic 
areas, the epiphyseal junction and the periosteum, are out of order, 
neither one being able to produce normal bone and both laying down 
osteoid matter. 

When, however, the progression of the disease is stopped, calcifica- 
tion occurs as usual, although there is a tendency to extreme hardness 
of the bone, small Haversian systems, and excessive periosteal bone. 

Associated Conditions. — The changes in the bones do not con- 
stitute the entire pathology of rickets. During the early and active 
stages of the disease there are some evidences of a generalized infection 
such as moderate irregular temperature, adenopathy, anemia, leucocyto- 
sis, and catarrhal inflammations of the respiratory and intestinal tracts. 
In the spleen and liver proliferative changes may occur leading to minor 
increase of connective tissue. The blood picture may include normo- 
blasts and the leucocyte increase is usually in the mononuclear variety. 
The muscles are generally atrophic or atonic. No changes specific for or 
peculiar to rickets have been found in the thyroid but this body is seldom 
normal. 

Osteotabes infantum is an imperfect bone formation, due to some 
deficiency of diet and akin to scurvy, in that hemorrhages in organs, 
bones and mucous membranes are common and because the condition can 
be relieved by a diet containing fresh vegetables and fruit juices. Ana- 
tomically the marrow is represented by a pale, edematous, loose fibrillar 
substance, poor in blood supply and myelogenous tissue, consequently the 
bone forming cells are undernourished and disappear. In the marrow 
and at osteogenetic areas the lack of capillaries is noteworthy. The 
bone formation is not so abnormal in character as lacking, thus con- 
trasting it with rickets. Hemorrhages occur within the narrow cavity 
and beneath the periosteum. When repair begins it may procede to 
normal conditions but where hemorrhages have occurred, hypertrophic 



DISEASES OF THE BONES 



887 



osteitis is apt to remain. Here, as in rickets there is a deficiency of 
calcium in the bones. 

REGENERATION OF BONE 

Regeneration of bone occurs most typically in the healing of frac- 
tures, and also as a part of various pathological processes in which a 
certain amount of destruction of bony tissue has taken place. Hyper- 
trophy may be included in the same group of affections. 

Fractures. — Definition. — -Fractures are breaches in the continuity 
of bone which occur in consequence of direct force or of muscular con- 
tractions. The bone may be broken in various directions, the line of 
fracture being straight or irregular, directly transverse to the long 
axis of the bone, or oblique. The bone may be broken into a number of 
splinters {comminuted fracture), or the fracture 
may be a single one. There is always more 
or less injury to the soft parts immediately sur- 
rounding the bone, and sometimes extensive 
injury causes communication between the outer 
surface and the seat of fracture through flesh 
wounds (compound fracture) . 

Repair of Fractures. — The process of repair 
is much the same as the process in the original 
formation of bone. Immediately after the 
fracture there is more or less hemorrhagic 
extravasation within the marrow and around 
the broken ends of the bone. Within a few 
days cellular infiltration, with congestion and 
edematous swelling of the periosteum and 
marrow, as well as of the bones, may be noted. 
Proliferative changes then take place in the 
same situations and new blood-vessels are 
formed. The adult bone-cells do not regenerate 
bone, this process devolving upon the osteo- 
blasts of the periosteum and marrow. They 
multiply and arrange themselves and their in- 
tercellular substance in a form similar to that of 
bone, into which first cartilaginous, then osseous, 

matter is deposited. The condition of this tissue varies greatly in 
different cases; sometimes it is quite fibrous, in other cases almost purely 
cartilaginous. Gradually it is converted into bone by the regular 
processes of bone-formation. At this stage the seat of fracture is occu- 
pied by a deposit of soft, bony material of considerable bulk, which 
causes a local thickening of the bone. Finally the excess (temporary 
callus) is removed by absorption, the parts in the direct line of the bone 
upon which the strain naturally falls become thickened (definitive or 
permanent callus), and other parts are absorbed. 

The original deposit of osteoid or chondroid material at the seat of 
fracture is termed callus (Fig. 444). Part of this is deposited on the 
exterior (periosteal callus) , and is derived from the periosteum; part is 
within the marrow cavity (myelogenous callus) ; and a third part is some- 




Fig. 444. — Fracture of 
the femur, showing mal- 
position of the ends of the 
bone and abundant callus 
(modified from Bollinger). 



888 



A TEXT-BOOK OF PATHOLOGY 



times seen between the ends of the bone {intermediary callus). The last 
is produced by the periosteum. 

The healing of fractures under the most favorable circumstances— 
that is, in cases in which the fragments of bone are restored to their 
proper position— is accomplished with but little disturbance of the 
normal relations. The seat of fracture may be permanently thickened, 
and there is some shortening of the affected bone, when the fragments 

are not placed in proper position, or angular 
deformities may result with considerable 
thickening from deposit of bony material 
between the fragments (Fig. 445) . 

When the fragments are not kept in ap- 
position, or when the general condition of 
the patient is unsatisfactory, the union of 
the fragments may be prevented and " un- 
united fractures" result. The ends of the 
fragments in these cases become rounded by 
absorption of the sharp edges, forming false 
joints (pseudarthroses) . When ossification is 
imperfect fibrous union takes place. 

Hypertrophy 

Local or general hypertrophy of bone may 
be found. Local hypertrophies may occur in 
consequence of increased strain upon certain 
parts of a bone, either directly or through 
the muscles. In muscular individuals hyper- 
trophy of this kind is frequently seen at 
points of attachment of the muscles. In cases 
of injury or incapacity of one of the limbs the 
other may show hypertrophy. 

Giant growth of certain bones, or of the 
entire skeleton, may be observed. Local 
hypertrophy of. this kind, dating from child- 
hood, is especially common in the upper 
extremities, and is frequently unilateral. It 
may be observed as a bilateral condition in the fingers. Complete 
giant growth usually begins about the age of puberty. The individual, 
previously developed as others, begins to grow abnormally until an ex- 
cessive size is reached. The bones are not only very large, but often 
markedly thickened and irregular. 

Acromegaly is an allied condition in which giant growth of the 
hands and feet, forearms and legs, and parts of the face, notably the 
lower jaw and parts of the cranium, is observed. A certain amount of 
hyperplasia of the soft tissues in the affected region accompanies this 
change. Hyperplastic conditions, tumors, and other diseases of the 
hypophysis cerebri, especially of the anterior lobe, have been met with 
in a considerable proportion of the cases. In some of the skeletons of 
giants investigated with regard to this point enlargement of the sella 
turcica has been found, and this evidences the occurrence of enlargement 




Fig. 4 4 5. — Fracture of 
humerus; section through the 
bone, showing the repair of 
the fracture (modified from 
Bollinger) . 



DISEASES OF THE BONES 



889 



of the pituitary body in some, at least, of such persons. The exact rela- 
tion between pituitary disease and bony hypertrophies remains obscure. 
(See Hypophysis.) 

CIRCULATORY DISTURBANCES 

Hyperemia is normal during the development of bone, or may 
accompany inflammatory disturbances of the neighboring parts. The 
marrow becomes more or less light- or dark-red in color, and the perios- 
teal vessels may be injected. The entire bone may have a pink or reddish 
color. 

Thrombosis may occur in the blood-vessels of the marrow, giving 
rise to areas of degeneration or myelitis, or in the cancellated tissue at 
the ends of long bones, in which case it may be of importance in the 
production of osteomyelitis or arthritis if the thrombus be infective. 

Hemorrhage beneath the periosteum and in the marrow is com- 
paratively common. It may result from traumatic causes or from scor- 
butic or purpuric conditions, as well as from inflammatory affections 
of the parts involved. Considerable subperiosteal hemorrhages are 
found in cases of infantile scurvy. The separation of the periosteum 
from the bone may lead to necrosis of the superficial layers of the bone. 
A similar accumulation of blood beneath the periosteum is that found 
over the bones of the skull in the newborn — the cephalohematoma. This 
results from the traumatism of labor. Large accumulations of blood 
of this nature may be absorbed or may undergo suppuration. 

Hemorrhage into the substance of bone may accompany other dis- 
eases affecting it, such as caries, tumors, and the like. 

INFLAMMATIONS 

Periostitis 

Definition. — Periostitis, or inflammation of the periosteum, may 
be of various forms, and may lead to different results. Sometimes the 
evidences of inflammation are very apparent; in other cases the disease 
appears in the form of a chronic productive process, leading to over- 
growth. 

Etiology. — Periostitis may be the result of traumatism, with or 
without the establishment of a communicating wound. In the latter 
case the injury provides an area of lessened resistance, which may sub- 
sequently become infected. In the former case the infection is direct, 
coming from the outside. Hematogenous infection without local injury 
is frequently observed. Infective periostitis may result from extension 
of an inflammation situated near the bones or from osteomyelitis. In 
all forms of bone disease more or less local periostitis occurs as a com- 
plication. In some cases the etiology is obscure, as in the periostitis 
which occurs during pregnancy and leads to the formation of osteo- 
phytes. 

Pathological Anatomy. — We may distinguish simple, suppurative, 
and ossifying periostitis; the simple may pass into the severer grades. 

Simple Periostitis.- — The membrane becomes swollen, red, and 
sometimes infiltrated with blood cells, this infiltration raising the perios- 



890 



A TEXT-BOOK OF PATHOLOGY 



teum from the bone. Microscopically, there are round-cell infiltration 
and proliferation of the periosteal tissue. If the process has been ex- 
tensive and the irritation long continued, a termination in fibroid thick- 
ening may be observed. This is not unusual in cases of fractures. 

Purulent Periostitis. — The disease may be circumscribed or diffuse. 
There are marked swelling and cellular infiltration, particularly in the 
deeper layers, and abscess-formation results. Separation of the perios- 
teum from the bone ensues, because of the tendency of the pus to dissect 
between the bone and its covering; this may lead to local interruption of 
the circulation between the periosteum and the bone, and consequent 
superficial necrosis of the bone with exfoliation results. In the diffuse 
form of periostitis widespread areas of the periosteum may be quickly 
involved and rapid destruction takes place. In these cases a consider- 
able inflammation of the surrounding tissues is customary. In all in- 
stances there is a tendency to burrowing of pus toward the surface, and 
its eventual discharge. The retention of necrotic portions of the bone 
may lead to continued suppuration, but with removal of the dead portions 
healing usually occurs. Ostitis and osteomyelitis are very frequent results 
of periostitis ; on the other hand, they may be in certain cases the original 
cause. 

Ossifying periostitis leads to the formation of bony excrescences, 
exostoses, or osteophytes. There is first a proliferation of the osteogen- 
etic layer of the periosteum, then partial ossification, and finally complete 
bone-formation with firm attachment to the underlying bone. The 
osteogenesis is essentially the same, but the periosteal bone-depositing 
cells are working in a tissue the seat of productive fibrosis, so that the 
calcium salts are not laid down in an orderly manner along the surface 
of the bone. These changes may be circumscribed or diffuse, and cause 
irregular elevations or general thickening of the bone. The exudate 
may be merely fibrous tissue or a soft albuminoid material, usually 
leading to periosteal thickening, but occasionally involving the bone or 
the marrow. Occasionally the surrounding connective tissues are 
implicated (par ostitis) . Ossifying periostitis may occur in the vicinity 
of joints affected with chronic arthritis. It may occur as a result of dis- 
eases of bones attended with considerable destruction, such as tumors, 
tuberculosis, etc. Occasionally the causes are entirely obscure. An 
interesting form is that which occurs in the bones of the hands and 
feet, forearms, and legs in tuberculosis of the lungs and empyema, or 
more rarely in other diseases; to this the term hypertrophic osteoarthrop- 
athy has been applied. This is a form of osteoperiostitis of ossifying 
type, and it seems to be due to the action of circulating toxins developed 
in the diseases with which it is associated, or to chronic passive congestion. 
Perhaps both factors are important. 

Associated Conditions and Results. — The conditions met with 
in. the adjacent bones and other parts have been referred to. General 
infection and intoxication may follow upon the suppurative cases, and 
death may then occur from septicopyemia. Permanent thickening of 
the bone may result in any case, or resolution may be practically com- 
plete. 



DISEASES OF THE BONES 



891 



Osteomyelitis and Ostitis 

Definition.— Acute osteomyelitis and ostitis are usually combined, 
and occur as an inflammatory condition affecting the marrow and its 
extensions into the communicating canals of the bone. The lamellar 
substance of the bone is only secondarily involved. It is to be remem- 
bered that the nutrition of the osseous part is cared for by vessels from 
the periosteum and from the marrow so that when it is cut off by lesions 
in these two places, the bone undergoes necrosis and has to be removed, 
for it has no power of regeneration ; new lamellar bone must be laid down by 
periosteal or cartilaginous bone formation. 
Marrow on the other hand can be replaced 
from adjoining tissue. 

Etiology. — Osteomyelitis is an infective 
disease resulting from hematogenous infection 
in the course of various diseases, from local 
infections in cases of traumatism (fracture, 
amputation), or from periostitis. Various 
micro-organisms, including staphylococci, strep- 
tococci, typhoid bacilli, and the Bacillus coli 
communis, have been discovered. The so-called 
primary or idiopathic cases are frequently 
secondary to a boil or an angina, and occur 
commonly in adolescents. 

Pathological Anatomy. — The marrow first 
becomes red and edematous, then cellular in- 
filtration and proliferation are superadded, 
and finally collections of pus or diffuse purulent 
transformation follow. Large areas of necrosis 
appear in the marrow and in spongy bone because 
of the cellular infiltration and vascular throm- 
bosis. The surrounding bone is involved, be- 
coming more or less infiltrated, softening, and 
not rarely undergoing necrosis (Fig. 446) . Small 
or large sequestra may be formed, or the bone 
may necrose completely. Periostitis is generally 
associated by extension through the Haversian 
system, and this layer is lifted from the bone 
which, thus deprived of nourishment from 
without, undergoes rapid necrosis. The tissues 
around the bone are usually infiltrated and 

suffer suppurative or necrotic changes. The process extends to the spongy 
ends, and to the joint surfaces in severe cases, and the suppuration cuts off 
the circulation. From here metastatic processes can arise from infected 
emboli. Hypertrophic changes may occur in the periosteum and super- 
ficial layers of bone, causing a bony encasement (involucrum) of central 
sequestra. In such instances a suppurating sinus, extending from the 
bone to the surface, usually remains. 

The rapidly developing cases of youth commonly begin as a epiphysitis, 
probably the result of infective embolic thrombosis ; in fulminating cases 
there may be a general gangrenous myelitis. 




Fig. 446. — Necrosis of 
femur, the result of acute 
osteomyelitis (Warren) . 



892 



A TEXT-BOOK OF PATHOLOGY 



Associated Conditions.- — Implication of the neighboring parts is 
habitual — deep-seated abscesses, arthritis, etc. General infection is 
usually the final result, and commonly leads to a fatal end. Marked 
changes in the blood have been observed- — leukocytosis, with large 
proportions of large mononuclear cells, myelocytes. 

Chronic Ostitis 

Chronic inflammatory processes are more apt to involve the bone 
than the marrow, though the beginning of the disease may be frequently 
in the latter situation. It may be suppurative, degenerative, or hyper- 
trophic in character. 

Etiology. — Chronic ostitis may follow osteomyelitis and necrosis, 
necrotic sequestra keeping up a constant irritation. In these case 
the disease is primarily infective. The chronic inflammations of bone 
due to tuberculosis and syphilis have special characters, which will be 
described below. In many cases the cause of chronic ostitis is obscure, 
though probably circulating toxic substances are the specific factors. 
Direct traumatism, periostitis, or other inflammatory diseases surrounding 
the bone may be the immediate causes. 

Pathological Anatomy. — In the necrotic and suppurative form, 
following osteomyelitis, there is more or less softening of the bony sub- 
stance by absorption of the calcareous matter, and at the same time 
proliferation, in the form of granulation tissue, of the cellular elements 
of the marrow and its prolongations within the Haversian channels. 
Localized abscesses may be formed, or infiltration of pus in various 
directions with increasing necrosis of the intervening bone may occur. 

The degenerative form of ostitis is a variety in which the calcareous 
matter is absorbed, and the bone thus rendered more soft and porous. 
The term inflammatory osteoporosis or rarefying osteitis is applied to this. 
In the process of absorption there are formed upon the outer and inner 
surfaces of the bone, or within its substance, areas of erosion, hollow 
spaces or indentations, showing bone-corpuscles and giant cells lying 
upon the eroded bon\^ tissue. These depressions are the so-called How- 
ship's lacunae. The giant cells, which are active in the absorptive process, 
are termed osteoclasts, and are anatomically identical with the osteoblasts 
or osteoplaxes of developing bone. It may be that the leukocytes of 
the burrowing pus are also able to produce absorption of bone structures. 
Simultaneously with this absorption of the lamellae of bone there is 
proliferation of the marrow substance in the eroded areas, and at the 
same time there may be increased vascularization of this intervening 
tissue. Perforations are frequently established through the lamellae 
by the penetration of new-formed blood-vessels, so that neighboring 
excavated areas communicate; thus at times isolated islands of bone may 
be formed or areas in which a number of sinuses intercommunicate, the 
calcareous bits perhaps disappearing entirely. This form of inflammation 
of the bone is frequent in the neighborhood of necrotic areas or osteomye- 
litic collections of pus, and plays a part in the pathological processes of 
osteomalacia and other bone diseases. It is rarely an independent condi- 
tion. 



DISEASES OF THE BONES 



893 



The hypertrophic form of chronic inflammation leads to increased 
density of the bone, to which the term condensing ostitis, or osteosclerosis, 
is applicable. It may occur as a reactive process surrounding areas of 
osteoporosis or other local diseases of the bone, or in association with 
ossifying periostitis. Occasionally, it occurs in certain bones or parts of 
bones without local or well-ascertained general causes. Such cases are 
met with in syphilitic persons. The anatomical changes consist in the 
deposition of increased quantities of bony tissue by the same processes 
as are operative in normal bone-formation. It is, therefore, a process 
in which the reparative forces have gained the field, a reverse of rarefy- 
ing ostitis. The lamellae become wide, and the vascular spaces are 
encroached upon and sometimes wholly replaced by bony tissue; the 
osseous tissue which' is laid down is very compact and the bone channels 
are narrow. 

The disease designated as leontiasis ossium is a form of osteosclerosis 
affecting the bones of the head and face, and causing irregular thicken- 
ing and enlargement of these bones. The cause of this condition is 
obscure. 

Ostitis Deformans 

Ostitis deformans is a condition of adult life which affects the skull, 
vertebrae, and certain long bones, causing enlargement of the affected parts 
and, on account of the elasticity of the diseased bony parts, great deformity. 
The most curious deformity seems to be in the thickness of the skull 
which may increase three or four times in cross section; the diplce 
usually disappears. Nevertheless this bone is so soft that it may be 
cut with a knife. Fractures do not occur. Pathologically there is ab- 
sorption of the compact bone, with confluence of the Haversian canals and 
new formation of osteoid and fibrous tissue throughout the diseased 
structures, the new and imperfect lamellae being disorderly in arrange- 
ment. There is a deforming ossifying periostitis accompanying the 
internal absorption. The medullary cavities of the long bones lose much 
of their blood making tissues and are filled with vascular connective 
tissue and abundant fat-cells, and sometimes cysts containing gelatinous 
material are observed. The etiology of the disease is obscure, but some 
form of trophic disturbance undoubtedly plays a part in the causation. 

There does not seem to be a deficiency of calcium in the bones nor 
any dependency of the diseases upon this element in the food. There is 
said to be on the other hand, a retention of calcium, magnesium and 
phosphorus with a relatively high excretion of sulphur. 

Fibrous osteitis of an obscure origin occurring in early adult life and of 
more localized nature, has been differentiated from the foregoing. It 
affects chiefly long bones that are subcutaneous and exposed to injury, 
causing swellings and fracture along the diaphyses. The lesion takes the 
form of absorption of normal bone, the deposit of a fibrous osseoid ma- 
terial and the appearance of a soft highly cellular marrow which may 
either liquefy, forming cyst-like areas, or assume the gross and minute 
appearance of sarcoma, giant cells being very frequent; metatasis, how- 
ever, seems not to occur. 



894 



A TEXT-BOOK OF PATHOLOGY 



DEGENERATIVE CONDITIONS 



Caries 

Caries is a term applied to the molecular destruction of bone, corre- 
responding to ulceration of the soft parts. It may be associated with 
periostitis and osteomyelitis, or with necrosis due to traumatism or 
various infective conditions. The changes consist in disintegration of 
the bone either into a mass of tiny bits of calcareous material with ex- 
posure of deeper parts or softening of bone cells with a fatty detritus. 
The process leaves a superficial irregular defect akin to ulceration. 

Necrosis 

Definition. — Necrosis is term applied to the death of a small or 
large portion of bone in mass. 

Etiology. — Among the causes are the various acute or chronic 
diseases of the periosteum, bone-marrow, and adjacent bone. In cases 

of purulent periostitis the separation 
of the periosteum from the under- 
lying bone leads to interruption of 
blood-supply and superficial necrosis. 
Similar results occur in cases of osteo- 
myelitis. Necrosis of the bone may 
also occur in consequence of embolic 
obstruction of the blood-vessels. 

Pathological Anatomy. — Ne- 
crosis may be partial or total, and 
may occur in the center of the bone 
or at the periphery. The dead por- 
tion of the bone, termed sequestrum, 
presents itself as an irregular, more 
or less eroded fragment, almost com- 
pletely or completely separated from 
the remaining structure. The separa- 
tion occurs by the process of demar- 
cation, as in necrosis of the soft parts. 
This line consists of an area of absorp- 
tion of the calcareous matter and 
proliferation of the cellular elements. 
The necrotic portion, or sequestrum, 
acts as a foreign body, and by its 
continued irritation keeps up a 
suppurative inflammation of the 
surrounding tissues. Fistulous com- 
munication with the exterior is usually 
observed. If the sequestrum is peripheral and has been discharged^ 
the periosteum or the bone may replace the lost tissue by regeneration. 
If the fragment is large or centrally placed, discharge is impossible and 
suppurative inflammation continues, sometimes for years. Bony tissue 
usually responds to the presence of a sequestrum by the formation of 
sclerosing ostitis and periostitis, and considerable hyperplastic material 
may be deposited over and around the sequestrum, and thus irregular 




Fig. 447. — Osteomalacia in a 52 year 
old woman (from the Vienna General 
Hospital Collection). 



DISEASES OF THE BONES 



895 



thickening of the bone may be produced. At times, however, the con- 
tinued irritation and suppuration may lead to complete destruction of all 
the bony tissue in the neighborhood. 

A peculiar form of necrosis is that occurring in consequence of chronic 
phosphorus-poisoning. It is met with in persons engaged in the manu- 
facture of phosphorus matches, and affects the maxillary bone. The 
existence of carious teeth aids in the development of this form of necrosis, 
probably by admitting micro-organisms which infect the bone already 
altered by the poison. The process begins in the periosteal and sub- 
periosteal portions of the bone, and ends in more or less complete necrosis. 

Associated Conditions. — Long-standing necrosis causes great 
deterioration of the general health, particularly in cases in which sup- 
purating sinuses are formed. Systemic infections may follow and amy- 
loid degeneration of various organs may occur. 

HYPOPLASIA AND ATROPHY 

Hypoplasia, or the lack of development of bones, may occur as a 
local or general condition. Local hypoplasia may be due to injuries or 
diseases which render a part of the body useless. General hypoplasia is 
found in cretins and dwarfs. 

True atrophy of the bones may involve an entire bone or only 
portions of it. General atrophy of the whole or of parts of a bone occurs 
as a result of inactivity or want of use, as in cases of palsy, chronic rheu- 
matism, and the like. Although the wasting is looked upon by some as 
a trophic change following nerve injury, it seems that, pathologically at 
least, the process is the same after nerve section and immobilization for 
an infectious condition. The process is one of greater activity of the 
osteoclasts than of the osteoblasts. It may begin in the marrow canal 
and proceed outward, eccentric atrophy, or beneath the periosteum, 
concentric atrophy. The Haversian canals are widened and a condi- 
tion of osteoporosis arises. The implication of certain parts of the 
nervous system (trophic centers) is particularly important, as the atrophy 
resulting in such cases is much more extensive than that occurring in 
cases of similar inactivity from other causes. 

Atrophy may also occur by absorption of calcareous matter and dis- 
appearance of osseous anatomy, fibrous tissue filling in, this is seen in 
osteomalacia. 

Partial or local atrophy of the bone may be due to pressure by 
aneurysms, tumors, and the like. In these cases there is gradual absorp- 
tion of bony substance, and the process is really one of inflammatory 
osteoporosis. 

General Atrophy. — Absorption of the bony substance, with re- 
sulting osteoporosis, may occur in marasmic individuals, particularly 
in seniles. In these cases it is held by most authorities that the path- 
ological condition is dependent upon the failure of replacement of bone 
to make up for the normal absorption constantly taking place. In 
these cases the bone becomes extremely fragile from the increase of its 
marrow-spaces and its general porosity. A condition of excessive fragil- 
ity is termed fragilitas ossium, or osteopsathyrosis. Occasionally this 
condition of fragility is met with as an idiopathic disease, without defi- 



896 A TEXT-BOOK OF PATHOLOGY *\ ? > 

nitely discoverable causation and without evident disease of the bones. 
Such cases have been found to occur in certain families through several 
generations. 

Osteomalacia 

Definition. — This disease is probably a constitutional condition 
leading to absorption of the bone-salts and to other changes in the bone 
which cause extreme flexibility. 

Etiology. — The causes of osteomalacia are still obscure. It is a 
disease occurring with especial frequency in puerperal women, but it 
may occur in men and in non-puerperal women.' A number of theories 
have been offered to explain the disease, but none of them has been 
established. In some respects it seems not unlikely that it is a tropho- 
neurosis, based upon the fact that the removal of the ovary brings bene- 
fit in some cases. It is also thought that adrenal insufficiency plays 
a part, and treatment with adrenal extract has a good effect in some cases. 
Most authorities look upon it in pregnancy as an exaggerated natural 
process of giving up inorganic salts to the fetus. An excess of earthy 
material is excreted in osteomalacia. There is loss of calcium and in- 
crease of sulphur and magnesium in the bones during active osteomalacia. 
It is particularly frequent in certain regions (endemic) , while in others it 
occurs very rarely (sporadic) . 

Pathological Anatomy. — The changes in the bone lead to various 
deformities and changes of appearance. Distortions, bends, and even 
fractures are observed in the long bones, and deformities due to abnormal 
curvatures of the spine are not infrequent. The shaft of the long bones 
may become of paper thickness. The pelvis shows peculiar changes 
which may prove very troublesome during labor. The characteristic 
change is a beaked condition, due to displacement forward of the pubes 
and a lateral indentation. This gives a triangular form to the outlet 
of the pelvis or superior strait. The bone-marrow is often quite red, and 
the periosteum in the nieghborhood of bends or fractures may be thick- 
ened by cellular proliferation. The minute structure of the bone in 
osteomalacia shows a more or less pronounced absorption of calcareous 
matter, but the normal lamellar arrangement of the bone may be pre- 
served. With the abnormal bone absorption there is a tendency to con- 
siderable deposit of osteoid material, but calcification of this substance 
is never completed. In the region of bends and fractures osteoid tissue 
of irregular structure, with bony corpuscles of considerable size, may be 
observed; while in other situations the regular lamellar arrangement 
and the ordinary small-sized bone-corpuscles are seen. Irregular areas 
of homogeneous or granular appearance may be interspersed within the 
normal osseous tissues. The line of demarcation between such abnormal 
non-calcareous portions and the unaltered bone may be either sharply 
drawn or diffuse. In the process of repair it is to be noted that the os- 
teoid tissue taking the place of the removed bone, is absorbed and new 
bone lamellae laid down. 

Associated Conditions. — Patients suffering from osteomalacia 
are usually reduced or cachectic, and frequently perish with terminal 
pneumonia. Some cases end in recovery by restitution of the bone. 



DISEASES OF THE BONES 



897 



It has been claimed that there is evidence in all cases of puerperal women 
of some bony absorption, and osteomalacia, therefore, would seem to be 
but an exaggeration of normal conditions. Normally, the slight bony 
changes are corrected after the puerperal period is passed. 

infectious diseases; , 

Tuberculosis 

Tuberculosis may occur in bones in several forms. Miliary tubercles 
may be found in the bone-marrow in the course of general miliary tuber- 
culosis, and local tuberculous disease of the periosteum may be met with. 
The most frequent and most important form of tuberculosis is tuberculous 
ostitis with caries. 

d 




Fig. 448. — Tuberculous caries of one of the bones of the foot: a, Bony trabecula; b, 
tubercle with caseous center; c, caseation in a focus of tuberculous tissue; d, giant cells 
in tubercles; e, osteoclasts;/, fatty marrow (Kaufmann). 

Etiology. — The involvement of the bones is nearly always second- 
ary, the first manifestations of tuberculosis occurring in other struc- 
tures, notably the lymphatic glands and the lungs. The original focus 
of disease is, however, frequently small, and may remain quiescent while 
the lesion in the bones advances. The disease of the bones may be due to 
direct extension or to hematogenous infection. Not rarely the joints 
are first involved and the neighboring bones only secondarily; indeed, 
it has been said that tuberculosis first noticeably affecting the epiphyses 
spreads from lesions in the synovia of adjacent joints. The epiphysis 
of a long bone and the cancellated tissue of flat and irregular bones are 
much more easily affected with tuberculosis than the marrow of long 
bones. Doubtless, both the epiphysis and metaphysis may be infected 
from joint cartilages. Fraser suggests that the settling point of the 
tubercle bacillus may be an endarteritis due to tuberculous toxemia. 

Traumatic influences are of importance in determining the situation 
of hematogenous tuberculosis. The traumatism causes circulatory 

57 



898 



A TEXT-BOOK OF PATHOLOGY 



disturbances in the bone, and thus produces a suitable soil for the bacilli 
to find lodgement. Bone tuberculosis is most frequent in early life; it 
may actually begin in utero. 

Pathological Anatomy. — Tuberculosis attacks by preference the 
outer layers of the marrow, the spongy bony tissue, and the periosteum. 
In the last there is usually proliferative change with caseation, caries 
of the underlying bony layers, and fibrosis. The 
tuberculous lesion of bone first presents itself 
as an area of grayish color, with congestive 
reddening of the parts around and intense in- 
jection of the bone-marrow in its vicinity. Sub- 
sequently there are rapid cheesy change and 
more or less softening of the area of inflamma- 
tion. Microscopically, tubercles in various 
stages of degeneration are discovered, and in 
addition areas of diffuse tuberculous granulation 
tissue and caseous degeneration (Fig. 448). 
The marrow about the tubercle is at first the 
seat of diffuse hyperplasia which gives away to 
lymph-cell infiltration, and this is in turn followed 
by fatty and fibrous tissue overgrowth. Lamellar 
changes are at first in the form of rarefying ostitis 
with caseous infiltration, about which extension 
occurs and new foci are established. The entire 
diseased area may be separated from the un- 
involved bone as a sequestrum, but more 
frequently there is gradual carious softening, 
with formation of semifluid, cheesy material 
containing gritty particles of bone or calcareous 
matter ("bone sand"). Complete softening 
leads to the formation of a "tuberculous abscess" 
(Fig. 449) . In these cases a more or less irregular 
cavity is formed within the bone, the wall of the 
cavity being covered with a pyogenic membrane 
developed from the marrow and its extensions 
into the Haversian canals. The contents of 
the abscess are puriform or cheesy. The process 
tends to extend to neighboring parts, particularly 
to the joints. When the abscess has penetrated 
the encasing bone it may spread within the soft 
parts, thus forming large tuberculous abscesses 
(so-called cold abscesses). 
The periosteum reacts to the lesions within the bone by the forma- 
tion of a productive periostitis, the new formation being either densely 
packed lamellae or similar to spongy bone. An osteoporosis may appear 
beneath the periosteum when tubercles form on the under surface of 
that tissue. 

Reactive changes may occur locally, and more or less restitution may 
take place. Complete encapsulation of a small focus may occur by the 
formation of a surrounding zone of granulation tissue and cicatrization, 



Fig. 449. — Tuberculous 
"abscess" in the lower end 
of the humerus (modified 
from Bollinger). 



DISEASES OF THE BONES 



899 



or by new formation of bone occurring after the activity of the tuber- 
culous process has been arrested. When adjacent portions of articulat- 
ing bones are involved the integrity of the articulation is disturbed and 
subsequently ankylosis may be established by the formation of exostoses 
and their union. The spread of the lesions toward joint surfaces is favored 
by the predilection of the tuberculous process for the spongy bone at the 
epiphysis, where it is apt to cause infarct-like anemic areas by arteritis 
or phlebitis. Obliterating endarteritis is commonly seen near the lesions. 

Some fairly distinct forms of bone-tuberculosis may be recognized 
pathologically, depending upon different combinations of the histological 
features above outlined. A large caseous tubercle may become encysted 
by fibrous tissue, but retain a sequestrum. There may be at times a 
diffuse puriform exudate without definite tubercles, but with rapidly 
advancing osteoporosis; this may possibly be due to mixed infection. 
There are also forms rather slow in their progress, the atrophic and hyper- 
trophy, in which osteoporosis and osteosclerosis are respectively the pre- 
dominating features. 

Seats and Associated Conditions. — Among the bones more fre- 
quently affected are the vertebrae, the long bones, particularly the femur, 
and parts of the skull. In the vertebrae the bodies are generally affected, 
and angulation or distortion of the spine results (Potts' disease). The 
cold abscesses formed in these cases may burrow considerable distances, 
pointing far below the place of origin. Those springing from the cervical 
vertebrae may point beneath the mucous membrane of the pharynx or 
esophagus, or anteriorly in the neck above the clavicle or shoulder. The 
abscesses formed in tuberculous caries of the dorsal vertebrae may point 
under Poupart's ligament. Tuberculous disease of the petrous portion 
of the temporal bone is not infrequent following tuberculous disease of 
the ear; it is important as a possible cause of tuberculous meningitis. Tu- 
berculosis of the head of the femur and of the hip-joint is one of the most 
frequent forms of surgical disease in children. The phalanges are some- 
times involved in early childhood by a curious form of tuberculosis, in 
which the shaft of the bone increases in size by gradual absorption and 
tuberculous softening within and deposition of new bone from the perios- 
teum without. 

Syphilis 

Syphilitic disease of bones may appear in various forms. Allusion 
has already been made to the condensation of the bones, or osteosclerosis, 
in this disease. Syphilis may also occur in the periosteum as a nodular 
periostitis, or in the substance of the bone in the form of degenerating 
gummata. Congenital syphilis gives rise to certain peculiar alterations. 

Etiology. — Syphilitic changes in bone are confined almost exclu- 
sively to the tertiary period. They may occur without other luetic 
disease, or as concomitants of hepatic, splenic, or other visceral disorders. 
The disease of the bones is frequently determined by local injuries; es- 
pecially is this true of the periosteal forms. 

Pathological Anatomy. — Syphilitic periostitis is very common 
upon the shin-bone, less frequent in the periosteum of other long bones. 
There is, first, slight swelling of the periosteum, due to multiplication of 



900 



A TEXT-BOOK OF PATHOLOGY 



the cells. Subsequently, this cellular mass undergoes cheesy or mucous 
degeneration, and the mass presents the appearance of a small gumma. 
Superficial erosion, or even necrosis, of the bone may take place, and 
discharge of the contents may occur. Following this, hypertrophic 
processes in the bone and adjacent periosteum lead to the formation 
of bony nodes. These nodes may, however, be formed without the occur- 
rence of softening and discharge from the periosteal lesion, the process 
in this case being one of simple ossifying periostitis. Gummata of the 
bones generally begin in the deeper layers of the periosteum, but tend 
to involve the bone more extensively than the form just described. 
The gummatous infiltration and proliferation occur along the blood- 
vessels of the periosteum and extend into the substance of the bone. 
Considerable areas may thus be implicated. The bone itself is absorbed, 
or may undergo rapid caries or necrosis, with weakening of the bone, but 
with little tendency to sequester formation. Around the area of syphil- 
itic change may occur a zone of reactive hyperplasia of the bone and 
periosteum. This may take the form of ossifying inflammation, giving 
rise to diffuse hardening of the shaft or of the layers directly under the 
periosteum, or hyperostoses may develop. The gummata themselves 
become cheesy or undergo mucoid degeneration, and eventually may 
discharge upon the surface. Syphilitc gummata are most frequent in 
the bones of the head, tibia, and sternum. 

Occasionally, gummata arise in the marrow of the bones instead of 
in the periosteum. 

Congenital Syphilis. — The bony changes of congenital syphilis are 
quite characteristic. The virus attacks the fetal cartilage causing an 
irregular proliferation as a sort of granulation tissue and the deposit 
of bone salts without proper arrangement. The alterations occur at the 
junction of the epiphyses with the diaphyses of the long bones. Longi- 
tudinal section through these parts shows the line of junction as a bluish- 
white or yellowish- white irregular zone about 2 or 3 mm. in thickness 
(Plate 14). In more advanced stages this line becomes thicker, quite 
uneven or broken and more yellow. The epiphyses may be completely 
separated from the shaft. The minute changes consist in proliferation of 
the cartilage-cells, which are gelatinous or fatty, about which bone is 
laid out irregularly, the spaces between the lamellae containing granula- 
tion tissue and atypical bone-cells. This process may go so far that 
separation of the diaphysis occurs. About the head of the bone there is 
usually an edematous or fibrillar swelling of the perichondrium in which 
round cells and new capillaries appear. 

Associated Conditions. — Involvement of the neighboring parts is 
not infrequently seen in syphilitic diseases of the bones; thus there 
may be gummatous infiltration of the superficial tissues with syphilis 
of the bones of the extremities, while in the case of skull-bones extension 
inward may lead to involvement of the dura and brain. When the 
process occurs about the foramina for exit of nerves the sheaths of the 
latter may become involved. Gummata of the sternum sometimes lead 
to the formation of retrosternal collections of puriform material. 
Amyloid degeneration of various organs frequently follows bone-syphilis. 



PLATE 17 



1811 $9&P4¥>. 




Epiphyseal junction in congenital syphilis, section stained with hematoxylin. 



DISEASES OF THE BONES 



901 



Actinomycosis 

Actinomycosis attacks bones, most often those of the .face and thorax. 
It occasions a rarefying, suppurative, or necrotizing complete osteitis, 
with involvement of adjacent tissues. There is little, if any, reactive 
limiting granulation tissue. 

Lepra 

Changes may occur in the bones in cases of mutilating leprosy, or 
more rarely in nervous lepra. Among these changes are ostitis and osteo- 
myelitis associated with new tissue resembling lepra nodules; consider- 
able destruction of the bones may be produced. 

TUMORS 

Exostoses are frequently met with in connection with definite 
disease of the bones and joints, or as more or less idiopathic outgrowths 
(see Fig. 57). They may be cartilaginous or fibrous in character, but 
subsequently may become osseous. They present themselves as flat, 
rounded elevations, or as more or less irregular outgrowths. Sometimes 
they are multiple and involve a number of bones of the skeleton. In 
such cases, particulary, heredity has been claimed as an important 
cause. 

Similar hypertrophic growths may appear within the marrow canal, 
especially in spongy bone, enostoses. 

Fibroma, lipoma, myxoma, and angioma may be mentioned 
among the true tumors as benign growths occasionally met with. They 
arise most frequently from the periosteum. 

Chondroma and osteoma are more common than these, and 
involve any part of the bone (see Figs. 55 and 58, pp. 183, 186). 

Sarcoma. — The most important of the primary tumors of bone 
is sarcoma. This may originate in the periosteum, bone-marrow, or the 
bone itself. It may be spindle-celled, or less frequently round-celled, 
alveolar or melanotic which varieties are always invasive and destructive 
whether they arise within the bone or from the periosteum. The giant- 
cell variety, or osteosarcoma, is particularly important. Sarcoma is most 
frequently met with in the lower jaw, beginning within the bone and 
causing a more or less rapid swelling. The tumor is surrounded by a 
shell of bone, which, however, sooner or later becomes perforated when 
the new growth spreads to the neighboring parts but this form is not 
highly malignant and commonly does not recur after removal (see Fig. 
71). In all forms of sarcoma there is absorption of the bony substance 
in the vicinity. A form of sarcoma springing from the periosteum is 
described under the name of osteoid sarcoma. This tumor consists of 
fibromatous and round-celled sarcomatous tissue in which osteoid ele- 
ments are irregularly embedded. More or less calcification and bone- 
formation are observed. The tumor may be quite soft or very hard; it 
tends to spread to the marrow cavity and absorb the shaft; it also ex- 
tends to neighboring soft parts and may give rise to metastasis. It is 
particularly frequent at the ends of the long bones (see p. 206). 



902 



A TEXT-BOOK OF PATHOLOGY 



Sarcoma from the periosteum forms nodular swellings, while that 
arising within the bone gives a fusiform growth because of its tend- 
ency to spread lengthwise. 

Secondary sarcoma of the bone-marrow is not rare in general 
sarcomatosis. 

Myeloma. — This term has been applied to a form of multiple 
primary tumor of the bone-marrow allied to the lymphatic growths 
of leukemia. The term lymphadenia ossea has also been given to it. 
There are three types — the myeloid, in which myelocytes predominate; 
lymphoid, made up chiefly of small deeply staining cells, and the plasma 
cell type. However, all these cells are represented in each tumor. The 
growths attack the shaft of the bones and fractures or bends may 
occur. 

Chloroma is a form related to myeloma, having a greenish or 
yellowish color, that occurs chiefly in the marrow but also in perios- 
teum or at joints, especially about the orbits and other parts of the skull. 

Primary carcinoma of the bones has been observed in a few cases. 
It can only be explained upon the assumption that islets of epithelial 
tissue have been deposited in the bone by faulty development. Most 
cases, however, described as primary carcinoma were probably in reality 
alveolar sarcomata. 

Secondary carcinoma of the bones is not rarely met with, espe- 
cially in cases of cancer of the breast, thyroid gland, and prostate. 
The secondary nodules may occupy the periosteum or the bone-marrow. 
The bone becomes exceedingly fragile, and fractures are not infrequent. 

Secondary tumors of bones are commonest as metastases from the 
breast, adrenal, prostate, kidney, and thyroid, and involve most fre- 
quently ribs, vertebrae, femur, humerus, and cranium. Thyroid-tumor 
metastases are usually single. 

Cysts and Parasites. — Cystic transformation of myxomata and 
of sarcomata may be met with. Occasionally, dermoid cysts are 
observed. Among the parasitic diseases Cysticercus cellulose has been 
described in a number of instances. They also occur in generalized fib- 
rous ostitis. 



CHAPTER X 



DISEASES OF THE JOINTS 

Luxation. — The most frequent injury of joints is that known as 
luxation, in which the relations of articulating bones are disturbed. 
In these cases the ligaments and other soft tissues around the joints 
are more or less torn, and in consequence become inflamed. If the 
luxation is reduced, this inflammation subsides quickly, and frequently 
normal conditions are restored. If the luxation persists, various second- 
ary changes may occur. Ankylosis in abnormal positions may take 
place by the formation of fibrous adhesions, or in more favorable cases 
a false joint may be established. In the latter case local atrophy takes 
place in one of the bones, forming a depression into which the end of the 
other fits. Later, ossifying periostitis produces an elevation around the 
depression of the socket, and thus a well-formed joint may be pro- 
duced. Luxation may be congenital, due to hypoplasia of the joint sur- 
faces or their surrounding tissues. 

Ankylosis is the term applied to the condition in which the normal 
movability between articulating bones is prevented by interosseous 
attachments. Pathologically, ankylosis may be fibrous, cartilaginous, 
or bony. All of these forms are met with after chronic inflammatory 
conditions of the joints. The ankylosis may be due to growing together 
of the joint surfaces by fibrous, cartilaginous, and bony deposits of the 
arthritis, or the fixation may be due to periarticular changes if the same 
pathological processes occur around the joint, as in arthritis deformans 

DISTORTIONS OF JOINTS 

Distorted conditions of the joints may be due to congenital mal- 
formations, to contractions of the muscles and tendons, or to cicatricial 
tissue in the neighborhood of the articulation. Changes in the joints 
themselves may be present as primary or as secondary conditions. 
Among the more important of such deformities of joints are the various 
sorts of club=foot: pes varus, the sole of the foot turned in; pes valgus, 
the sole of the foot turned out; pes equinus, the foot extended and sup- 
ported upon the anterior ends of the metatarsal bones; pes calcaneus, 
the foot flexed and resting on the heel. Combinations of these condi- 
tions are frequently met with. At the knee-joint are found: genu 
valgum, in which the knees are bent in (knock-knee), and genu varum, 
in which the knees are bent out (bow-legs). 

CIRCULATORY DISTURBANCES 

Hyperemia of the joints occurs as a part of acute inflammations, 
and involves the synovial membranes particularly. The synovial fluid 
may be increased in quantity. 

903 



904 



A TEXT-BOOK OF PATHOLOGY 



Hemorrhage into the joint may result from traumatic causes or 
from inflammatory conditions, particularly in the course of hemor- 
rhagic diseases, notably scurvy and hemophilia. The blood may remain 
fluid for a long time, unless considerable damage has been done to the 
synovial surface whereupon tabs of coagulum are laid down on the 
articular surfaces; the joint not rarely has the appearance of chronic 
arthritis with effusion. Later, resorption of the blood takes place. 

Dropsy of the joints occurs in the course of acute and chronic 
inflammations. 

INFLAMMATIONS 

Acute arthritis may be traumatic or due to hematogenous infec- 
tion; in other cases it is secondary to disease in the vicinity. Hema- 
togenous arthritis may occur in the course of various infectious diseases, 
such as scarlet fever, small-pox, pyemia, etc. In the same group must 
be considered acute articular rheumatism, which is doubtless an infec- 
tion conveyed to the joint through the blood. 

Pathological Anatomy. — Various grades may be distinguished, such 
as the dry or fibrinous, the serous, and the purulent. In all cases there is, 
first, a deep congestion, swelling, and infiltration of the synovial mem- 
brane. The ligaments and the cartilage are more or less implicated 
at the same time. The terms synovitis, implying involvement of the 
synovial membrane, and panarthritis, implying general involvement, 
may be applied. In the dry or fibrinous form there is a deposit of fibrin 
upon the surface, with or without serous exudation. In the genuine 
serous form the exudation is purely serous, but more commonly sero- 
purulent liquid is observed. Entirely purulent exudate is sometimes 
formed (empyema of the joints), a lesion nearly always combined with 
ulceration of the synovial surfaces and involvement of the subserous 
fibrous tissue and not rarely of the immediately subajacent cartilage and 
bone. There are usually infective granulations protruding into the joint 
cavity from such eroded areas. 

Acute Rheumatism is perhaps the most important single form of 
arthritis because of its apparent infectious nature and its effects upon 
the heart and kidneys. Pathologically the lesion in mild cases is a 
serous process but fibrinous or even purulent exudation may be encoun- 
tered; periarticular edema is commonly present. The fluid is lightly 
turbid, containing leukocytes and perhaps a little fibrin but bacteria are 
not usually discoverable. The gonococcal variety is similar to this but 
is more inclined to be purulent. 

Results.- — In the milder cases complete resolution may take place 
without destruction of the tissues of the joint. In the more serious 
cases there is inflammation of the articulating cartilages, with conse- 
quent ulceration or caries, or even considerable necrosis of the cartilage. 
The underlying bone may be laid bare, and ostitis or osteomyelitis may 
result. Sometimes discharge of purulent material into the surrounding 
tissues occurs, and fistulous communications with the exterior may be 
established. These processes may lead to extensive disorganization of 
the joints, with luxations and, in later stages, ankylosis. 



DISEASES OF THE JOINTS 



905 



Associated Conditions. — About joints, the seat of acute inflammation, 
there is always a periarthritis or, at least, an edematous swelling. Gen- 
eral systemic infection may follow these acute inflammations of the 
joints. 

Chronic arthritis may follow the acute forms already described or 
may be primarily chronic, the latter group falling into a rather confus- 
ing number of clinical varieties so that they will be classified under 
another heading. The following are non-specific monarticular types of 
chronic nature. 

Chronic serous arthritis, or hydrops articulorum, is frequently due 
to repeated acute arthritis. The joint is filled with thin synovia, and 
the synovial membrane is somewhat thickened. The surface of the 
joint may be more or less covered with an 
injected thickened synovial membrane 
(synovitis pannosa). The knee-joint is 
most frequently involved. 

Chronic purulent arthritis is always 
infectious and is usually the outcome of 
an acute seropurulent or purulent arthritis. 
The conditions met with have already been 
described. It terminates in more or less 
extensive disorganization of the joint, and 
in favorable cases in fibrous ankylosis 
(Fig. 450). 

Occasionally, one sees a combination of 
the two preceding forms with tendency to 
scanty exudate, ulceration of the cartilages, 
and early formation of connective tissue. 
This is the so-called uclerative adhesive 
chronic arthritis. In both these forms 
but more especially the latter, much re- 
active thickening occurs in the periarticular 
cartilages and ligaments into which cal- 
careous matter may be deposited. 

Arthritis Deformans. — This term may be used to include a group 
of conditions probably of varied etiology, characterized by certain 
deforming changes in the tissues constituting joints, and to an extent 
also in the adjacent bones and ligaments. Very many classifications 
have been made but with rare exceptions they do not square with known 
etiology nor is there any essential difference in the pathology. All of 
the types are of rather insidious character although in one form there are 
definite evidences of a low grade infectious state. The lesions that go 
on in chronic arthritis are now atrophic and degenerative, now reactively 
hyperplastic and productive of bone or cartilage, but, with a few excep- 
tions it cannot be said that they present clinical or pathological entities. 

The general term arthritis deformans is preferred as sufficiently 
descriptive, and because it involves no theory regarding the precise type 
of pathological change or of etiology. The old name rheumatoid arthritis 
is objectionable because of the implied relationship with rheumatism. 

The etiology of the forms of joint disease, here included under one 




Fig. 450. — Fibrous ankylosis, due 
to chronic purulent arthritis. 



906 



A TEXT-BOOK OF PATHOLOGY 



general term, may be very varied. Formerly, the occurence of the 
common polyarticular form in persons who had endured hardships, 
exposure, or various kinds of physical and nervous depression, and the 
associated trophic changes in the skin and muscular tissues suggested 
a nutritional disorder or some nervous condition as the important etio- 
logical factor. In recent years attention has been drawn more and more 
insistently to the probability of infection or infectious toxemia but, 
while here and there bacteria have been found in the joints, they are not 
uniform in kind. Hidden sources of infection (tonsils, teeth, nasal 
sinuses, gastro-intestinal tract) have been discovered in some cases, 
but not in all. In the forms behaving like subacute infections, involve- 
ment of the pleura, endocardium and lymph nodes is not uncommon, 
thus strengthening the infection theory. While many cases may be 
favored by nutritional, traumatic or nervous disorders, bacteria and 
their toxins are probably at the basis of all kinds. 

Pathology. — In hyperplastic cases the articular surfaces show granula- 
tions which may lead to adhesions; these are irregularly scattered over 
the joint but more upon the apposed surfaces. Later the cartilages 
atrophy, and may either be uniformly thinned or irregularly indented or 
furrowed. The articular surface may be extremely roughened and irre- 
gular. Later, or simultaneously, the edges of the cartilages may present 
hypertrophic changes. Usually, this takes the form of " lipping" or 
projecting ecchondroses at the sides of the joint, sometimes of considerable 
magnitude. Similar hyperplastic cartilaginous change may occur on the 
articular surface or in the synovial tissues, and the ligaments about the 
joint, the combination leading to ankylosis especially well seen in the 
spinal varieties. The synovial membrane and the ligaments about the 
joints are usually affected, and in some cases are the chief seats of 
alteration. 

In the more inflammatory and in the atrophic stages, there tends to 
be an accumulation of synovial fluid which m the former instance may 
contain leucocytes and red blood cells, while in the latter it is more serous. 
In the hypertrophic and ossifying varieties there is less fluid, the synovia 
becoming thickened, fibrous or calcareous. In some cases villous out- 
growths from the synovial membrane are abundant, and these may be- 
come cartilaginous and may be separated as free bodies within the joint. 

In the variety where the ankylosis is due to adhesions of the articular 
surfaces, the hyaline cartilage soon gives way to a granulation tissue 
supplied largely by the spongy bone of the epiphysis but there will tend 
to be bone deposited within the joint, perhaps covered by irregular carti- 
lage. When the periarticular tissue and the cartilaginous margins of 
the joints are chiefly at fault, and this is usually a dry form, the bone 
ends become eburnat^d, there being no reactive inflammation on the 
opposed surfaces. There usually is in these cases however, some degree 
of osteoporosis so that the bones are frail. 

In the so-called atrophic form there is a definite tendency to absorb 
the end of the bones with their coverings. Such are the instances show- 
ing large swollen soft joints in which subluxations are prone to occur. 
The hypertrophic form leads to deformity and contractures by fixation 
of joints. 



DISEASES OF THE JOINTS 



907 



In so far as the bodily metabolism of infective chronic arthritis is 
concerned all that can be said is that it falls within the normal limits 
with a slight slowness on the part of the renal functions. There is no 
apparent change in the calcium metabolism. 

Clincial Types. — (a) Arthritis deformans in its most familiar form is 
polyarticular and affects the small joints of the hands and feet primarily. 
Later, though often simultaneously or even before the small joints are 
involved, the knees, elbows, and other large joints suffer a similar 
change. This form is most frequently encountered after the third 
decade of life, but may occur in younger persons and even in childhood. 
The disease is insidious in onset and progressive up to the most advanced 
deformity. 



Fig. 451. — Arthritis deformans, showing extensive deformity of the hands. 

(b) In other cases a more acute onset and more active evidences of 
joint inflammation cause a nearer clinical resemblance to articular 
rheumatism. This form also is usually polyarticular and has practically 
the same distribution as the first type. In the end the joint changes 
may be indentical, but not infrequently fibrous tissue growth remains 
predominant in this type. The suggestion of an infection is most 
pronounced in this group. A class of cases, described by Still as occur- 
ring in young children and associated with glandular and splenic 
enlargement, anemia, and fever, should perhaps be included here. 

(c) Senile arthritis of the hip (malum coxae senile) and the similar 
types of dry arthritis of the knee or other joints, usually monarticular, in 
which moderate cartilaginous erosion and absorption, and hyperplastic 
changes in the ends of the bones occur, constitute another group. 



908 



A TEXT-BOOK OF PATHOLOGY 




(d) Heberden's nodes are bony enlargements at the sides of the ter- 
minal interphalangeal joints of the fingers. These may occur inde- 
pendently or in association with other joint changes. The process is 
similar to that seen in other types. 

(e) Spondylitis deformans is a deforming and ossifying type of 
arthritis of the spine. In some cases the intervertebral disks become 

atrophic and bony ankylosis 
takes place between the bodies 
of adjacent vertebrae. In other 
cases bony ankylosis of the 
smaller articulations of the spine 
and ossification of the ligaments 
is the initial process. The spine 
may be rigid and straight, or 
may be markedly kyphotic. In 
the type of Striimpell-Marie, 
the hips and shoulders are in- 
volved while in the von Bechterew 
form the condition seems limited 
to the spine but there are as- 
sociated evidences of degenera- 
tion of the ' spinal cord or nerve 
roots. 

Neuropathic arthritis is met 

with in the course of spinal 
diseases, such as locomotor 
ataxia and syringomyelia (Fig. 452). It resembles the forms just de- 
scribed, is slowly developed, and is usually quite painless, suggesting 
a purely degenerative or trophic disorder. The joint is enlarged, due 
in major part to an excessive outpouring of a serous fluid and somewhat 
to a swelling of the synovial membrane, cartilage and bone ends; 
atrophy of related muscles may increase the appearance of enlargement. 
Changes in the tissues just mentioned 
as larger than normal, consist of hydropic 
swelling of synovia, velvety softening of 
cartilages and anemic dropsical atrophy 
in epiphyses; fractures or separations 
of segments may occur. 

Gouty Arthritis. — Gout is a con- 
stitutional disease with a tendency to a 
peculiar form of arthritis. The latter 
consists in the deposit of crystals of 
urate of sodium and calcium in the 
cartilage cells and intercellular substance 
of the articulations, and in more advanced cases in 'the connective 
tissue of the joints and the tissues round the joints (Fig. 453). 
These crystalline deposits occur in definite attacks, as a rule, 
each attack (gouty paroxysm) being marked by inflammatory pro- 
cesses in the joint. Hyperemia of the synovial membrane, with 
serous effusions and with sometimes more evident inflammatory mani- 
festations (hyperplasia of the cartilage cells and round-cell infiltration), 



Fig. 452. — Neuropathic arthritis of the knee 
in a case of locomotor ataxia (case of Dr. 
C. W. Burr). 



- 3 (f\ 3 




Fig. 453. — Deposit of crystals of 
urate of sodium in an articular*cartilage 
(Lancereaux) . 



PLATE 18 




Gouty tophi in ear. 



DISEASES OF THE JOINTS 



909 



is observed during the paroxysms, and by their repetition chronic changes 
in the joint are produced. The cartilages may become more or less 
eroded, and even carious changes and suppuration may take place. The 
joints most frequently involved are the small joints of the hands and feet, 
notably the metatarsophalangeal joint of the great toe. The larger artic- 
ulations are less commonly involved, and usually after the smaller joints. 

Associated Conditions. — The pathology of gout is by no means 
confined to the changes in the joints. The disease is a general one, and 
pathological changes are found in various organs. There is a tendency 
to thickening of the blood-vessles, to atheroma, and to sclerotic changes 
in the kidney, liver, and heart; and uratic deposits may occur in the 
organs named or in the subcutaneous tissue or superficial cartilages, 
such as those of the ear and nose (gouty tophi). Concretions or calculi 
are occasionally found in the bladder, but rather more commonly in the 
pyramids of the kidney; small accumulations of urates may be found 
anywhere within the renal substance, (see also p. 49 for discussion of 
etiology) . 

INFECTIOUS DISEASES 
Tuberculosis 

Tuberculosis, when primary in the joints, usually begins in the 
synovial membrane. Occasionally, it arises by extension from lesions 
in the soft parts of the immediate vicinity or, more commonly, it is 
secondary to tuberculosis of the adjacent bone, from which source any 
part of the joint may be first involved. 

Etiology. — Tuberculous arthritis is most frequent in childhood, 
and occurs in those predisposed by heredity. The immediate deter- 
mining cause may be traumatism, this serving to localize the disease in 
a joint rendered peculiarly susceptible. Lesions in the spongy bone, 
the result of vascular disease, seem to precede joint tuberculosis in 
many cases; the course as outlined under bone tuberculosis is undoubt- 
edly the most frequent path of infection. Those cases arising by primary 
involvement of the synovial fringes are often rather acutely inflammatory 
in character with a serous exudate, while those cases which extend from 
the ends of the bones are more protracted in their course, and are usually 
accompanied by rarefying or sclerosing osteitis about the tuberculous 
lesion. Tuberculous arthritis is frequently secondary to scrofulous 
disease of the skin or glands, or to pulmonary tuberculosis, but is often 
primary in the joint or adjacent bone ends in the sense that the orignial 
focus remains hidden by inactivity. 

Pathological Anatomy. — The changes met with in the joints 
vary somewhat in different cases. In instances beginning in the syno- 
vial membrane there are formed more or less abundant, soft, spongy 
granulations, which may eventually fill the entire joint cavity. These 
are pinkish or whitish in color, and may show gray or yellow spots or 
tubercles quite plainly. Later, this granulation tissue tends to degen- 
erate, becoming mucoid or breaking down by suppurative or cheesy 
change. In the early stages the soft tissues of the joint are considerably 
inflamed and edematous; later, they may show ulcerative or necrotic 
change, and similar alteration may occur in the articular cartilages. 
Puriform softening of the granulations and the tissues of the joint may 



910 A TEXT-BOOK OF PATHOLOGY 

lead to the development of cold abscesses within the joint, and the 
latter may eventually burrow to the exterior. In cases progressing 
unfavorably the joint is greatly disorganized by the advancing necrotic 
changes which cause ulcerative removal of the bone ends and caseous 
degeneration in them and in the periarticular tissues. In favorably pro- 
gressing cases, productive connective tissue growth surrounds the lesion 
walling in the caseous material, while on the part of the bone osteoscler- 




Fig. 454.— Osteoporosis of acetabulum in tuberculous arthritis of the hip-joint. 



oses makes its appearance. Ankylosis takes places by adhesions of the 
articular surfaces, by bone deposit in the marginal cartilages and some- 
times by a similar involvement of the ligaments. 

The external appearances of tuberculous joints are often quite 
distinctive. The joint is swollen and boggy (" white swelling") or some- 
what elastic to the touch, and usually more or less distorted from sub- 
luxation. There is little evidence of acute inflammation. In cases 
terminating in ankylosis the bones are generally left in faulty position 
in consequence of the formation of adhesions and the irregular contrac- 
tions of muscles. 

Secondary Disorders. — Long-standing tuberculosis of the joints 
occasions profound disturbances of the general health and sometimes 



DISEASES OF THE JOINTS 



911 



causes definite disease, such as amyloid degeneration of various organs. 
Disseminated tuberculosis rarely results. 

Syphilis 

Syphilitic disease of the joints may occur in hereditary lues. The 
cartilages of the joints are eroded, and thickening of the ligaments 
with puriform exudation into the joint is observed. The phalangeal 
articulations are most frequently involved. In later life gummata in the 
neighborhood of the joints may invade the latter by contiguity. 

TUMORS 

Hyperplastic conditions are met with in the synovial fringes of the 
joints in association with arthritis or independent of such. These 
hyperplasias may take the form of fibrous growths, or they may become 
lipomatous. An interesting form of new growth is seen in the so-called 
free bodies or "joint-mice." These are small fibrous or cartilaginous 
bodies, which are entirely free in the joint or attached by a fine pedicle 
to the synovial membrane. They are formed from the synovial fringes, 
and probably result from injury or hypertrophic inflammation in most 
cases. Some of these bodies seem to originate in organized fibrin or hem- 
orrhagic coagula; upon such a basis definite fibrotic or even calcareous 
masses may arise. Still other forms appear to come from bits of cartilage 
broken or ulcerated off from the bone. The shape of j oint bodies is usually 
flat but occasionally they are knobby, which shape has been explained 
by a growth of cartilage within them. The joints may be secondarily 
involved in various forms of bony tumors and apparently primary 
enchondromata and sarcomata have been reported as orginating within 
them. 

THE TENDON-SHEATHS AND BURSTS 

Inflammations of the sheaths of tendons (tenosynovitis) and of the 
bursas (bursitis) occur under similar circumstances and in similar forms 
as inflammations of the joints. A form of chronic bursitis with dropsical 
effusion frequently occurs in the bursa beneath the patella from chronic 
irritation (housemaid's knee), and in the bursa at the joint of the elbow 
(miner's elbow) . These conditions are analogous to hydrops articulorum. 
Gout gives urate deposits in the tendons, their sheaths and bursa, with 
considerable exudate or infiltration or even necrosis. 

Ganglion is a condition of the tendon-sheaths of some clinical 
interest. It presents itself as a rounded cystic nodule, most frequently 
upon the back of the hands and wrists. Distinct fluctuation may be 
discovered, or the cyst may be so dense that it feels stony hard. The 
ganglion results from a localized dropsical condition of the sheath of the 
tendons, with frequently a lateral hernious projection. A similar con- 
dition is sometimes caused by projection of the synovial membrane of 
the joints. This condition is sometimes tuberculous, occasionally 
primary in a clinical sense, at other times secondary to bone tubercu- 
losis. This form contains rice-bodies. 

Tumors are rare, but a so-called myeloma, which seems more like 
an endothelioma, has been reported. 



CHAPTER XI 



DISEASES OF THE VOLUNTARY MUSCLES 

Congenital malformations are occasionally met with, such as 
absence of a part or of an entire muscle. 

HYPERTROPHY 

Hypertrophy is frequently produced by athletic exercise or laborious 
occupations. This affects the parts brought into play, and .is pro- 
portioned to the amount of work and the constitution or condition of 
the individual. The muscle-fibers increase in thickness and probably 
also in number. 

Sometimes muscular hypertrophy is met with in cases in which no 
adequate cause is discoverable. Thus in local or general giant growths 
the muscles may be involved with other parts. 

Pseudohypertrophy will be discussed among the degenerative condi- 
tions. 

CIRCULATORY DISTURBANCES 

Anemia of the muscles may be part of a local or general anemia; 
it is often quite insignificant in comparison with anemia of other parts. 
In some of the general anemias the muscles may present a dark appear- 
ance, due to degenerative conditions. 

Hyperemia is physiological during and after exercise. It occurs as 
an active process in association with inflammatory conditions and as a 
passive congestion in cases of vascular stasis. 

Hemorrhages may be traumatic, or may result from rupture of the 
vessels in consequence of inordinate blood-pressure or local degenera- 
tion of the vessel walls and the surrounding muscle-fibers. Among the 
conditions in which hemorrhage takes place are tetanus and other con- 
vulsive disorders, fevers, and hemorrhagic diseases such as scurvy or 
hemophilia, and septic diseases. They have been seen often in the recent 
epidemics of streptococcus disease and influenza. The hemorrhages 
may occur in the form of small extravasations between the fibers, or of 
more extensive infiltrations in the intermuscular planes. In cases of 
traumatism, scurvy, or hemophilia, considerable blood-tumors may be 
formed, the muscle-fibers being pushed aside or torn apart. The blood 
is more or less rapidly absorbed. Pigmentation and fibrous-tissue pro- 
liferation may result. 

Embolism of the arteries or thrombosis of the veins does not pro- 
duce serious disturbances as a rule unless the cause be actively infective 
or a large number of vessels be involved since the collateral circulation in 
muscles is abundant. In the absence of suppuration necroses arise. 

912 



DISEASES OF THE VOLUNTARY MUSCLES 



913 



Rupture of muscles results from wounds, sudden contraction, or blows 
where normal contraction exists. If the broken ends separate, blood is 
usually poured out. Regeneration after rupture, wounds, hemorrhages 
and necroses depends upon the amount of damage and the separation of 
the remaining healthy sarcolemma. If a small damage exists and the 
sheath bridges the gap, full restitution occurs but if the whole fiber has 
been severed, granulation tissue and cicatrization form the healing proc- 
esses (see also page 160). 

INFLAMMATIONS 

Inflammation of the muscles, or myositis, may be acute or 
chronic, and may present itself in a variety of forms. Acute myositis 
may be local or disseminated. 

Localized Acute Myositis.— This form may be due to injuries, 
such as contusions of the muscles or wounds communicating with them, 
or may be infectious in character, resulting from the direct extension 
of infectious diseases of the skin, subcutaneous tissues, bones, and other 
adjacent parts, or from embolism. A serous, a hemorrhagic, and a 
purulent form may be distinguished. 

Serous myositis is characterized by an edematous condition of the 
muscle, which gives it a peculiar gelatinous appearance on section. 
Microscopically there is cellular infiltration of the muscle-bundles, 
while the muscle-fibers themselves become swollen and suffer granular 
degeneration or hyaline change, and sometimes vacuolation. 

Hemorrhagic myositis is an intense form, and is met with in muscles 
adjacent to gangrenous or phlegmonous lesions, malignant pustules, and 
the like. Myositis occurring in scorbutic individuals is frequently of 
the hemorrhagic form, as is also that which occurs in consequence of 
the sting of venomous snakes or other animals. The muscle becomes 
more or less tensely swollen, and on section the hemorrhagic infiltra- 
tion is plainly visible as a diffuse process or as localized areas of hemor- 
rhage. 

Suppurative myositis may be circumscribed or diffuse. Circum- 
scribed myositis, or abscess of the muscle, may result from entrance 
of micro-organisms through the lymphatic or vascular circulation, or 
it may be due to traumatism, with communications from the surface. 
Occasionally suppurative inflammation occurs in an obscure manner, 
when the term cryptogenetic myositis is applicable Distinctly metas- 
tatic abscesses may be occasioned by emoblism. 

In association with suppurative inflammations of the skin or sub- 
cutaneous tissues and the mucous membranes there may be seropuru- 
lent or phlegmonous myositis, with the formation of irregular abscesses. 
In these cases the lesion spreads by infiltration, and the muscle-fibers 
undergo widespread degeneration (fatty degeneration, hyaline change, 
and necrosis). Abscesses in the muscles extend and rupture in various 
directions, and may leave considerable areas of scar-formation. 

Disseminated acute myositis or polymyositis may appear without 
any definite cause, sometimes in association with tuberculosis of the 
lungs, or as distinctly secondary affection in association with infec- 
tious diseases, like typhoid fever, diphtheria, etc. In the primary form 

58 



914 



A TEXT-BOOK OF PATHOLOGY 



there may be widespread muscular disease, with swelling and tenderness 
of the muscles and sometimes redness and edema of the skin. The term 
pseudotrichinosis was applied from the resemblance of the appearances 
to those of trichinosis, and the name dermatomyositis has also been 
given this condition. There is a tendency by some observers to separate 
the condition into the variety characterized by multiple abscesses and that 
combining muscular foci with cutaneous rashes. In so far as the first 
form is concerned there is good reason to believe that it is a bacteriemia 
due to a form of Staphylococcus pyogenes, the organism having a predilec- 
tion for the muscles, as indicated by animal experimentation. The other 
variety has as yet no such clear explanation. Both may however be 
due to the same cause and represent simply clinical variations. Some 
of the conditions included under the heading muscular rheumatism by 
clinicians are doubtless instances of the kind here discussed. Examina- 
tion of the muscles shows pallor of the tissue and sometimes visible areas 
of degeneration. Microscopically there are cellular infiltration between 
the muscle-fibers and swelling, with loss of striation of the fibers them- 
selves. More advanced degenerations of the fibers, such as granular 
change, coagulation-necrosis, and vacuolation, may be observed. The 
affected muscles lose their functional contractile power, and more or less 
palsy results. When affecting the muscles of the pharynx and respiration 
this becomes serious in predisposing to inspiration pneumonias. 

The condition described as secondary acute polymyositis is degen- 
erative to a greater extent than inflammatory, and will be considered 
among the degenerations. 

Chronic myositis may be suppurative in type or productive. 

Chronic suppurative myositis may be the outcome of acute sup- 
puration, and is particularly frequent in association with tuberculosis 
and actinomycosis. 

Chronic productive myositis is characterized by the formation of 
connective tissue between the muscle-fibers. The fibers themselves, 
as a rule, undergo degenerative changes, though occasionally showing 
regeneration to some extent. This condition may be the termination 
of acute myositis, or it may occur in the vicinity of various localized 
diseases of the muscles or of the neighboring parts. In some cases, if 
not all, the primary change is degeneration of the muscle-fibers, and the 
interstitial or fibrous tissue is reactive in character. Some of the cases 
will be considered under the head of muscular atrophies. The changes 
that occur in the interstitial tissue of the muscles consist primarily of 
proliferation and round-celled infiltration. Later, there is formation 
of firm connective tissue. Some multiplication of the muscle-nuclei 
and actual increase in size of some muscle-fibers may be observed. 
Degeneration of the muscle-fibers, however, is more prominent, and is 
generally in proportion to the degree of connective-tissue change. 
The fibers may show cloudy swelling or hyaline changes, or more com- 
plete degeneration, such as fatty degeneration, fragmentation, or vacuole 
formation. 

Ossifying myositis is a variety of productive myositis. It may 
occur in the form of bony nodules in parts subjected to constant irri- 
tation or strain, as in the case of the deltoid muscle in soldiers and the 



DISEASES OF THE VOLUNTARY MUSCLES 



915 



adductor muscles in horsemen. Similarly, in the vicinity of disease of 
the bones and periosteum, nodules may develop in the muscle. A form 
of more general disease, termed myositis ossificans progressiva, has been 
observed in youthful persons, without discoverable cause. It affects 
the muscles of the back and neck, and sometimes those of all parts of 
the body. The muscles are swollen, and first present inflammatory 
manifestations, terminating in fibrous change which finally leads to 
bone-formation. The osseous tissue is at first in the form of spicules or 
small nodules, but gradually increases to considerable proportions. The 
muscles themselves contract, and various deformities with pseudo- 
ankyloses may result. The muscles of the face, diaphragm, and 
heart are unaffected. A peculiar malformation has been found asso- 
ciated with 75 per cent, of the cases. This is a form of microdactylism — ■ 
ankylosis of the phalanges of the thumb and lack of one phalanx of the 
great toe on both sides. 

ATROPHY AND DEGENERATIONS 

Atrophy of muscles may consist of a simple reduction and disappear- 
ance of the contractile protoplasm in the fiber or it may include certain 
degenerative processes, chiefly fatty in nature. The former is encounter- 
ed when inactivity precedes the loss of substance while in the types 
comprising the essential clinical muscular atrophies, there is usually 
some degenerative alteration within the fiber. Certain cases are depend- 
ent upon disease of the spinal cord or nerves (neuropathic form), others 
occur as primary diseases of muscles (myopathic form), and in another 
group the change is due to simple nutritional processes (simple and 
senile forms). 




Fig. 455. — Neuropathic muscular atrophy, showing atrophy of the muscle-fibers, increase 
in the interfascicular fibrous tissue, and thickening of the blood-vessel walls. 

Neuropathic muscular atrophy may be the result of disease of 
the anterior horns of the gray matter of the cord or of neuritis, the process 
being that discussed under spinal atrophy (page 998). There are cases, 
however in which no definite changes in the cord seem discoverable and 
where no cause can be ascribed, which are called progressive muscular 
atrophy or dystrophy, although from the standpoint of the muscle, the 



916 



A TEXT-BOOK OF PATHOLOGY 



pathology is the same. There is some reason to believe that this latter 
is dependent upon incorrect metabolism of sugar by the muscles. The 
disease most often appears in children and may occur in more than one 
member or generation of a family; there is yet another clinical variety 
appearing more in adult life. 

It leads to progressive atrophy of the muscles of the hands, arms, 
and shoulders, and less frequently of those of the body and buttocks. 
It usually begins in the small muscles of the hands, but sometimes 
affects those of the shoulders first. The muscles become pale and rather 
flabby. Microscopically, the fibers show various forms of degeneration. 
Fragmentation in a longitudinal or in a transverse direction, coagula- 
tion-necrosis, and occasionally fatty degeneration of the fibers may be 
seen. Sometimes the fibers seem to grow smaller by a simple atrophic 
process (Fig. 455). Coincidently, reactive proliferation is seen in the 
connective tissue between fibers, and doubtless this to some extent 
causes further muscular degeneration. Abortive attempts at regeneration 
are sometimes seen in the muscle fibers, but for the most part the con- 
tractile substance can scarcely be recognized; intrafibrillar increase of 
sarcolemma nuclei can be made out at times. 

Secondary neuropathic muscular atrophies may occur in various 
spinal diseases, from cerebral tumor or hemorrhage and from neuritis. 
These are essentially similar in character to the primary neuropathic 
variety, though their clinical character is different. ' Section, disease, or 
injury of motor nerves may lead to local atrophies by separating the 
muscles from their trophic centers in the cord. The damage from de- 
struction or interruption of the peripheral neuron appears sooner and is 
more definitely associated with degeneration than that from central 
lesions. 

Myopathic muscular atrophy in its atrophic form is identical 
with that just discussed under progressive muscular dystrophy but the 
hypertrophic form deserves mention. 

Pseudohypertrophic Muscular Atrophy. — In this condition the 
muscles increase greatly in size, but are soft and flabby. The child 
may present the appearance of an athlete, with enormous calves and 
thighs, but is extremely weak and can scarcely stand. Microscopically, 
the causation of the enlargement is found to be a considerable degree of 
intermuscular proliferation of connective tissue, with marked fatty infil- 
tration. Sometimes in this form, as well as in other varieties, some 
actual enlargement of the muscle-fibers is observed, but this is doubtless 
degenerative. 

, To this group probably belongs the myotonia congenita of Thomsen. 
In this form some fibers are definitely hypertrophic, but the general 
muscular mass is atrophic. A suggestion of hyperplasia is given by 
increase of nuclei, but may arise from fiber splitting. 

Myasthenia gravis is an atrophy of the external ocular, facial and 
cervical muscles, very frequently associated with disease of the thymus. 
Pathologically there are dense mononuclear infiltration and edema. 

Simple muscular atrophy may be senile in origin or due to lack 
of use when a joint or whole member is immobilized for inflammation or 
injury; cachexia may also produce atrophy. In these cases the muscle- 



DISEASES OF THE VOLUNTARY MUSCLES 



917 



fibers become smaller, and some proliferation of the connective tissue 
and sarcolemma nuclei is generally present if the condition be con- 
tinuous. In senile cases brown atrophy may occur, brownish pigment 
particles being deposited in the atrophic fibers, especially near the 
nuclei (Fig. 456). 




«ir.iltto> 



" " ■ - ■ -- 

Fig. 456. — Muscle from a case of carcinoma of the esophagus, showing the presence 
of fat and pigment at the ends of the nuclei. From a drawing. X 1000. (Jewesbury 
and Topley, in Journal of Pathology and Bacteriology.) 




Fig. 457. — Section from a case of infective purpura, showing well-marked true fatty 
degeneration. From a drawing. X 450. (Jewesbury and Topley, in Journal of Path- 
ology and Bacteriology.) 

Parenchymatous degeneration of the muscles may occur in the 
vicinity of inflammatory lesions, tumors, or other areas of disease. 
It may also occur in the course of infectious diseases in association with 
coagulation-necrosis. The fibers become cloudy and lose their striated 
appearance from the presence of minute granules. In some instances 



918 



A TEXT-BOOK OF PATHOLOGY 



inflammatory changes in the interfascicular connective tissues are asso- 
ciated with the degeneration of the fibers. Cases of this sort may be 
called secondary acute polymyositis. 

Fatty degeneration is found under the same circumstances as the 
above, and also in chronic cachectic diseases and in cases of poisoning 
with phosphorus and other " parenchyma poisons." The muscle- 
fibers have a streaked or spotted, yellowish appearance, and are more 
or less flabby. Microscopically, the fibers are seen to be filled with 
small oil-droplets which obscure the striations. All parts of the fiber 
may become degenerated until the sarcolemma sheath contains only a 
mass of fat-droplets and detritus (Fig. 457). 

Fatty infiltration may occur in association with atrophy in the 
condition above described — pseudohypertrophic muscular atrophy; and 
in various nervous diseases in which the muscles waste from disease 
or trophic change. A certain amount of lipomatosis may occur in general 
obesity. This fat increase also occurs in cases of abnormal carbohydrate 
metabolism. 

Amyloid degeneration is rare and unimportant. 

Calcification may occur in the form of ossifying myositis, and 
locally in scars following various local diseases — abscesses, etc. 

Coagulation=necrosis, or hyaline degeneration, is of great 
clinical importance. It was first discovered by Zenker as one of the 
lesions occurring in typhoid fever. The muscle-fibers at first become 
granular and cloudy (parenchymatous degeneration), and later waxy or 
hyaline change occurs in pale pink or yellowish streaks or completely 
transforms the fibers. Transverse fragmentation is common, and gross 
rupture of the muscle may be found. In the latter cases hemorrhagic 
infiltration, or even considerable hemorrhage (hematoma), may be 
occasioned. Reactive inflammatory change in the interstitial connec- 
tive tissue is generally present, while in the sarcolemma active prolifera- 
tion of the nuclei may be found, an apparent attempt at regeneration. 
This disease occurs in the course of typhoid fever, but also in various other 
febrile and infectious conditions, notably epidemic influenza. It is most 
common in the abdominal muscles (rectus abdominis), in certain muscles 
of the extremities, and in the heart. The latter situation is, of course, 
of greatest significance. (See Diseases of . the Heart.) 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of cold abscesses in associa- 
tion with tuberculous disease of bone or less frequently of the lymphatic 
glands or other parts. In these cases there is a gradual extension of the 
caseous and liquefying tuberculous disease into the muscles, and some- 
times the abscesses burrow to great distances within the muscular sheath, 
as, for example, in psoas abscess. Less destructive tuberculous myositis 
may occur in the muscles beneath the skin and mucous membranes by 
extension of tuberculous processes. In these cases cellular infiltration 
and tubercle formation, with some caseous change, may be observed. 
Miliary tubercles, or larger tuberculous nodules due to hematogenous 
infection, are rare. 



DISEASES OF THE VOLUNTARY MUSCLES 



919 



Syphilis may occur in the form of gummata, and it is likely that 
some cases of diffuse productive myositis are syphilitic in nature. As in 
other parts of the body, the blood-vessels in these cases have been de- 
scribed as particularly thickened. 

Glanders, actinomycosis, and anthrax may involve the muscles 
in the vicinity of the specific lesions. Nodular and later, necrotic or 
suppurative foci are the lesions observed. 

TUMORS AND PARASITES 

The tumors of muscles, for the most part, spring from the inter- 
stitial connective tissue. Among the benign tumors, myxomata, and 
lipomata are sometimes met with while fibromata of a hard nodular, 
and hyaline variety are seen especially in the thigh and abdominal 
muscles. Osteoma and chondroma are found as localized lesions resulting 
from irritation or as true tumors. Striped muscle tumors, or rhabdomyo- 
mata, are rarely found in the muscles, though occasionally seen as small 
nodules. 

More important than the above is sarcoma, which occurs as a pri- 
mary tumor comparatively frequently. The fibrous and spindle- 
celled varieties are common, and round-celled sarcoma is sometimes 
observed. The tumors originate from the connective tissue, though 
it is held by some that the muscle-fibers themselves may undergo sar- 
comatous transformation. 

Carcinoma is a rare tumor, and is always secondary. The second- 
ary form is not rarely seen in the muscles in the vicinity of carcino- 
mata of other structures, such as the mammary gland. 

Among the parasitic diseases of muscles may be mentioned trich- 
inosis, cysticercus invasion, and hydatid disease. The first occasions 
disseminated myositis, to which reference has already been made. The 
other two conditions are rare and not important. 



CHAPTER XII 



DISEASES OF THE BRAIN AND ITS MEMBRANES 

The Dura Mater 

The dura mater forms the inner covering of the skull and acts as a 
firm support of the brain. It consists of dense connective tissue which 
contains however rather active fibroblastic cells and is covered by endo- 
thelium on the internal surface. While the dura itself is poor in blood- 
vessels, reflections of the membrane surround large venous sinuses. 
There is in places close apposition of the arachnoid, the villi of the 
latter often extending in between the fibers or folds of the dura. This is 
important because of the extension of inflammation from one to the other 
and the combination of tissues from both in some tumors. 

CIRCULATORY DISTURBANCES 

Active hyperemia occurs in the dura in association with tumors, 
gummata, and other focal diseases. The vessels of the dura surround- 
ing the area of disease become distended and the membrane may be 
diffusely reddened. 

Passive hyperemia may occur under the same circumstances as 
the above, and also in cases of thrombosis of the venous sinuses. 

Hemorrhages are usually due to traumatism, and may occur on 
the outer or inner surface of the dura. Extradural hemorrhages are 
more common than intradural, especially in cases in which there is 
fracture of the skull. The blood in these cases comes from the skull 
bones and the vessels on the outside of the dura. It does not collect 
quickly, and tends to gravitate to dependent parts. It exerts pressure 
by its bulk, and may cause cerebral degeneration beneath it. A collec- 
tion of blood between the skull and the dura is sometimes designated 
internal cephalohematoma. Small hemorrhages into the dura may occur 
in infectious or hemorrhagic diseases and in cases of death from asphyxia. 

Sinus thrombosis occurs in the so-called marantic or infective 
varieties both of which are favored by traumatism. The former kind 
appears usually at the extremes of life in persons enfeebled by wasting 
diseases, especially when combined with arterial or cardiac disease. 
While it usually begins in the superior sinus it may extend to branches or 
to veins. These thrombi do not tend to adhere tightly to the walls 
but contract as firm cords thereby permitting some current to pass; 
occasionally they seem to be absorbed. Infective thrombi usually appear 
in the sinuses near to or draining an infected focus and are most commonly 
seen in the lateral sinuses after purulent middle ear disease. Such 
thrombi are usually soft and necrotic but may be laminated if the infec- 
tion be of low grade. They tend to spread by self propagation and may 
reach the vessels of the neck and chest. Acute meningitis and septico- 
pyemia are frequent sequels. 

920 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



921 



INFLAMMATIONS 

Inflammation of the dura, or pachymeningitis, may be acute or 
chronic, and hemorrhagic, suppurative, or productive in character. 

Internal hemorrhagic pachymeningitis occurs more frequently in the 
aged than in the young, and is not uncommon in the insane. Chronic 
alcoholism and traumatism seem to be etiological factors of some im- 
portance. In the early stages of the disease the inner surface of the 
dura exhibits a superficial deposit or membrane of grayish color, with 
brown or red spots, the former being composed of altered blood-pigment 
(hematoidin). Often several layers are present, indicating successive 
exacerbations. Microscopically, the membranous deposit is found 
to consist of soft granulation tissue containing numerous thin-walled 
blood-vessels. Later, diapedesis of blood-corpuscles, or actual hemor- 
rhages occur, and the diseased area may have the appearance of a 
simple collection of blood or of a more or less stratified hemorrhagic 
exudate. Sometimes the amount of exudate and of hemorrhage may 
be such as to cause considerable cerebral compression, and in other cases 
death may occur from the hemorrhage itself. Occasionally the blood 
is in part absorbed, and a serous collection (hydroma durce matris) results. 
The seat of the disease is usually in the area of distribution of the middle 
meningeal artery. The process is slow, and recurs or is continued by 
irritation of the granulation tissue. The dura grows internally by diffuse 
or localized thickening, but rarely adheres to the pia arachnoid. 

Suppurative external pachymeningitis may occur in consequence 
of injuries, caries, or other diseases of the skull. Sometimes it results 
from purulent softening of thrombi in the venous sinuses, and very 
rarely it is secondary to leptomeningitis. Not rarely localized suppu- 
rative pachymeningitis results from disease of the middle or internal 
ear, with extension through the petrous bone. The dura becomes 
thickened by cellular infiltration, is soft and edematous, and not rarely 
undergoes necrotic change. The disease may be localized or diffuse, 
and may occasion secondary thickening and adhesions of the dura in 
cases terminating favorably. When suppurative processes arise, exten- 
sion to sinuses may lead to thrombosis and general infection. Occa- 
sionally the internal surface of the membrane shows the greatest change 
but this cannot be said to be independent of pial lesions. 

Productive pachymeningitis may be of fibrous, or ossifying charac- 
ter. The etiology is often obscure. Some cases follow hemorrhagic or 
suppurative pachymeningitis; in others the process seems to be primarily 
productive. Traumatism may cause proliferation of fibrous tissue in 
the dura. This is especially apt to occur after fractures of the skull in 
children, when, as a result of its adhesion to the bone, the dura is almost 
invariably torn. Syphilis is probably a cause of importance. The dura, 
in the fibrous variety, is simply thickened and more or less attached to 
the pia-arachnoid and the inner surface of the skull. When firm attach- 
ments with the skull are formed, osteophytes are frequently found 
upon the surface of the bones and in the dura (ossifying pachymenin- 
gitis). Osseous plates may be met with in the falx cerebri and ten- 
torium cerebelli. 



922 



A TEXT-BOOK OF PATHOLOGY 



INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary tubercles in asso- 
ciation with tuberculous leptomeningitis. It may also be associated 
with tuberculosis of the bones; and in rare instances, has been met with 
as a primary disease of the dura. In the latter cases the disease takes 
the form of a caseous nodular thickening of the membrane (Fig. 458). 




Fig. 458. — Nodular tuberculous pachymeningitis. The mass to the left is the prod- 
uct of the chronic change in the dura and fitted into the depression in the hemisphere 
(from a specimen in the collection of Dr. Allen J. Smith). 

Syphilis may occasion a form of diffuse productive pachymeningitis, 
or gummata. The latter may originate in the dura and extend to the 
pia or skull bones, or they may originate in the bones and invade the 
dura secondarily. Gummata in this situation present themselves as 
more or less flattened nodular growths of grayish color, having a marked 
tendency to caseous change and to resolution, with formation of cir- 
cumscribed thickenings and adhesions of the dura. 

TUMORS 

Tumors of the dura mater occur with considerable frequency. 
Among the pathologically benign growths are fibroma, osteoma, and 
chondroma. The most common tumor is probably some form of sar- 
coma which may appear in any of its forms. Such tumors while usually 
single, may be multiple, and they present soft irregular masses tending 
to involve the bone if they begin upon the external surface or the pia 
and cortex if they grow from the under surface ; occasionally they flatten 
out over the convexity. 



DISEASES OP THE BRAIN AND ITS MEMBRANES , 923 

Statistical studies have shown that endotheliomata are among the 
most common tumors in this region. They usually occur as single well 
outlined and encapsulated irregular masses; but occasionally they are 
multiple, and it is possible that in these cases metastasis has occurred. 
Ordinarily they produce no disturbances in the brain, but in some in- 
stances pressure-symptoms have been reported. Histologically they are 
divisible into endothelioma proper and angiosarcoma or perithelioma. 
Mallory believes that they originate in the endothelium of arachnoid 
villi since he has been unable to convince himself that the dura mater 
is covered by endothelial cells. The former consists of densely packed, 
rather large, pale elements supported by scanty connective tissue which 
may be compressed into masses resembling pearls and comparable to the 
early stages of psammoma bodies. The other group appears to take 
origin from about blood vessels for there is an increased number of capil- 
laries and arterioles about which dense mantles of rather cylindrical 
cells are seen. Away from vessels, the cells become round and deeply 
staining; the stroma may divide the tumor into segments. This form 
may also contain calcareous matter in granules. 

Psammoma is often described as an independent multiple sessile or 
pedunculated growth eroding the interior of the calvarium. It is prob- 
able that where many psammoma bodies have formed, the original type 
of tumor is hidden since several tumors may contain these structures. 

Among the other tumor-like growths are fibrous changes that may 
or may not be inflammatory in nature, and lead to circumscribed or 
diffuse thickening of the dura mater, and usually cause it to adhere 
densely to the skull. These are most apt to be found in old people. 
In addition to the round-cell sarcoma, gliosarcoma of the brain and 
carcinoma of the scalp may give rise to secondary growths in the dura 
mater, but these are extremely rare. 

CYSTS 

Cysts of the dura are usually due to its protrusion through the 
skull and the escape of cerebrospinal fluid into the protruded portions. 
This is spoken of as meningocele. Two varieties are recognized, true and 
false. True meningocele is produced by the bulging of the dura mater 
through some congenital fissure in the skull. It is difficult to distinguish 
this from encephalocele (q. v.). False or spurious meningocele is almost 
invariably the result of some injury before the third year of life, such as 
fracture of the skull and effusion of blood. Later the blood is absorbed 
and replaced by a clear fluid, leaving only a brownish layer upon the 
inner surface of the cyst. As in early life the dura is adherent to the 
skull, it is usually torn at the time of fracture ; and ordinarily there is also 
a laceration of the arachnoid, allowing the escape of the cerebrospinal 
fluid into the sac, which is formed externally chiefly by the pericranium. 
As a result of pressure, of bone absorption, or of defective growth, the 
opening in the skull usually enlarges considerably, and ultimately there is 
extreme deformity of the head. In cases where the brain has been lac- 
erated at the time of injury, porencephalic cavities may occur, which in 
some instances have communicated with the lateral ventricles. The 



924 



A TEXT-BOOK OF PATHOLOGY 



commonest situation for these cysts is the parietal bone; but they may 
occur in the frontal or occipital regions, and in rare cases are multiple. 

The Pia-arachnoid 

This composite tissue consists of two layers anatomically, but be- 
cause of their close physical and physiological relations are to be con- 
sidered as one membrane. The outer layer, the arachnoid, consists of 
loose connective tissue full of spaces continuous with the perivascular 
channels of the pia, being therefore in close association with those in the 
cortex; in these spaces is a limpid fluid, the cerebrospinal fluid. The pia 
follows the convolutions of the brain very closely, and there is a continua- 
tion of this membrane as the velum interpositum into the ventricles, its 
vessels being continuous with the choroid plexus. From these facts it is 
easy to see how infections of the pia-arachnoid may extend inward. 
The cranial nerves as they leave the skull are covered with pia for a short 
distance. 

CIRCULATORY DISTURBANCES 

Anemia of the pia may occur in cases of general anemia. 

Active hyperemia is constantly present in the early stages of men- 
ingitis. It is also met with in cases of death from alcoholism and in 
severe infectious fevers, though in most of these cases microscopical 
examination discloses the fact that the process is really one of begin- 
ning inflammation. The pia is red and the small arterioles are injected. 
The fluid in the subarachnoid space is in excess, and may be slightly 
turbid or sanguinolent. 

Passive hyperemia occurs in cases of general venous stasis, as in 
heart disease, pulmonary disease, and venous thrombosis. The large 
veins are greatly swollen, and the subarachnoid fluid is excessive. 

Hemorrhages.— Small punctate hemorrhages may occur in cases 
of meningitis, in scurvy, purpura, and the like. Larger hemorrhages 
between the pia and arachnoid are most commonly due to trauma- 
tism, and may sometimes be the result of rupture of aneurysms. It 
would seem that endo- and periarteritis lie at the bottom of most of these 
cases of so-called intrapial hemorrhage except perhaps in the traumatic 
cases. The blood may be wholly within the membrane or burrow under 
it along the surface, into the sulci or even to the ventricles. Punc- 
tate hemorrhages are said to occur during severe infections and upon 
absorption to leave small opaque areas in the pia; such white spots are 
indeed frequently seen at autopsy. Extrapial hemorrhage is most often 
due to trauma or is seen in the new-born after protracted or mechanical 
delivery. It may be localized or spread over the convexity, in either case 
causing compression which may be fatal. Occasionally the blood be- 
comes inspissated and absorbed, the membranes in these instances be- 
coming thickened and pigmented, or it may be encapsulated and the 
pigment absorbed, giving rise to a clear cyst (hygroma). 

Edema of the membranes, or collections of liquid in the subarach- 
noid space (external hydrocephalus) may be due to passive congestion 
or it may be found in cases of chronic alcoholism and nephritis. In long 
standing cases the membranes are thickened and of a translucent or 



DISEASES OF THE BRAIN AND ITS MEMBRANES 925 

gelatinous appearance; the subarachnoid fluid causes elevation of the 
arachnoid and more or less compression of the cerebral convolutions. 
Hydrops ex vacuo is a form of dropsical effusion under the arachnoid, 
resulting from atrophy or hypoplasia of the cerebral convolutions. The 
space normally occupied by cerebral substance is in these cases filled with 
cerebrospinal liquid. 

INFLAMMATION 

Inflammation of the arachnoid and pia is called leptomenin= 
gitis. It is always an infectious process, and may be either acute or 
chronic. The bacteria gain entrance (1) by penetrating wounds or 
fractures involving the mucous membranes in the anterior base of the 
skull or in the pharyngeal and vertebral regions; (2) by passing along the 
lymph spaces through the cribriform plate at the nasal vault when taken 
up by phagocytes from the nasal mucosa; (3) by extension from foci of 
infection in sinuses, cranial bones or the pharynx; or (4) via the blood 
stream. 

Etiology. — The commonest cause of sporadic acute leptomeningitis 
is the pneumococcus. It is found in about 60 per cent, of all cases, and 
in these pneumonia is often an associated or primary condition. Other 
micro-organisms that have been found are the streptococcus, the staphy- 
lococcus, Friedlander's bacillus, the Bacillus pyocyaneus, the bacillus of 
glanders, the influenza bacillus, the actinomyces, the typhoid bacillus 
(of which a number of cases have been reported), the Bacillus coli com- 
munis, and the bacillus of bubonic plague. Meningitis occasionally 
occurs in the course of gonorrhea in which the gonococcus is probably the 
bacterial cause, although this has been questioned. Mixed infection is 
not uncommon, consisting usually of the pneumococcus and one or other 
of the more common pyogenic micro-organisms, and the latter are also 
frequently found associated with the tubercle bacillus. 

Pathological Anatomy. — The gross changes may vary from those 
that are not recognizable macroscopically to collections of greenish 
pus in the subarachnoidal space one-half inch or more in thickness 
and covering the entire surface of the brain. In the slightest forms the 
presence of the condition may be suspected by the slight edema of the 
arachnoid, and perhaps a small collection of fluid containing flakes 
along the fissures of the brain. In some cases, however, even this does 
not occur, and it is impossible, without a microscopical examination, to 
say that inflammatory processes exist. Microscopically, sections in 
these cases usually show overfilling of the small vessels with blood, and 
a greater or less number of round cells, usually polynu clear, imme- 
diately surrounding it. Often this collection of round cells is most 
marked in the recesses of the convolutions. Staining for bacteria usually 
reveals the presence of a few, although in these cases they are rarely 
numerous. If the process has been more severe, or of longer duration, 
the edema of the arachnoid becomes more pronounced, its glassy, moist 
appearance being very distinctive. The vessels are usually injected; 
this applies particularly to the veins, which appear as dark-blue tor- 
tuous cords running through the membranes. In the arachnoidal space 
there is now a considerable collection of fluid, and along the sides of the 



926 



A TEXT-BOOK OF PATHOLOGY 



arteries usually a distinct collection of lymph or pus. Sometimes, but 
not always, the arterioles are also distinctly injected, and occasionally 
there is a faint pinkish coloration, due to the injection of the capillaries. 

This form may be localized or diffuse, and is almost always secondary 
to some local source of inflammation, which is most frequently middle- 
ear disease. The process often shows distinct indications of rapid 
extension, and may spread to the lining of the ventricles and cause an 
internal collection of fluid. 

The diffuse forms have been divided, according to the part affected 
with greatest intensity, into leptomeningitis of the vertex and lepto- 
meningitis of the base. The processes are by no means limited to these 
areas, however, but may extend in any direction. It is common for the 
suppurative lesions to spread along the arachnoid spaces to the spinal 
meninges. The ventricles may be attacked by way of the blood-vessels 
of the choroid plexus. 




Fig. 459. — Leptomeningitis purulenta cerebralis (Karg and Schmorl). 



The changes observed consist of diffuse injection of the soft mem- 
branes, edema of the arachnoid, and a perivascular serofibrinous exudate 
along the course of the vessels coming from the veins. Microscopically, 
sections show around these vessels a mass of fibrin, in which are em- 
bedded a considerable number of polynuclear leukocytes. Often cells 
undergoing fatty degeneration are also found in these masses, lying close 
to the walls of the vessels in the portions of the brain where the changes 
are most pronounced. In this condition micro-organisms are usually 
found quite readily, either within or without the cells, those within the 
cells, in particular, frequently showing a partial loss of staining power 
that has been taken to indicate phagocytic activity. 

In the most severe cases the entire subarachnoidal space is dis- 
tended with a purulent accumulation. The surface of the brain can 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



927 



no longer be seen, the thick greenish exudate covering the convolutions 
as a smooth mantle. In nearly all these cases there is also pronounced 
edema, the arachnoid looking thick, shiny, and moist. Microscopical 
sections show the ordinary picture of a purulent accumulation; pus- 
cells in a fibrinous meshwork, desquamated endothelial cells, and micro- 
organisms. In all forms of acute leptomeningitis petechial hemorrhages 
into the arachnoid are common. The substance of the brain and cord 
may also be involved (meningo-encephalitis, meningomyelitis) , and 
this involvement may vary from a slight increase of the neuroglia 
elements just beneath the pia to the presence of foci of round cells. 
These foci are usually found about the small vessels or lymphatics 
dipping in from the pia, the latter situation being by far the more fre- 
quent. Ordinarily they are microscopical and surrounded by a narrow 
zone of partially degenerated nervous substance, outside of which there 
is again a slight increase in the neuroglia tissue and cells. Occasionally, 
however, "the cerebral involvement may be more extensive, and large 
abscesses are formed, leading to the destruction of considerable portions 
of the nervous substance. The nerve-fibers, even those in the neigh- 
borhood of the lesion, rarely show distinct alterations. The ganglion- 
cells, however, exhibit slight diffuseness in taking the stain, or irregulari- 
ties in the arrangement of the chromophilic bodies, if the abscesses 
are larger, either involving or close to the gray substance, the ganglion- 
cells may show extensive degeneration, with entire loss of staining power 
and fragmentation of the protoplasmic processes, nothing being left to 
indicate the position of the cells excepting an irregularly shaped vesicle 
containing some brownish pigment. These larger foci, however, are 
usually found in the white substance. 

An attempt has been made to distinguish varieties of meningitis 
according to the infective agents, and Netter has stated that in pneumo- 
coccic infection the pus is viscid and greenish; in streptococcic infection, 
more serous and less adherent to the membranes. Influenzal meningitis 
is said to be commonly accompanied by pial hemorrhages and a peri- 
vascular infiltration extending rather deeply into the gray matter. 
Honl believes that only four forms can be differentiated — the thick, 
viscid pus of the pyogenic micro-organisms, the yellowish exudate of 
tuberculosis, the bluish-green pus of the Bacillus pyocyaneus, and the 
purulent exudate containing yellowish grains of actinomyces. 

Epidemic cerebrospinal meningitis does not differ essentially from 
the ordinary septic form, excepting in its cause, the meningitis coccus 
(q. v.). As a general rale, the inflammatory process begins upon the 
convexity of the frontal lobes, and proceeds backward and downward, 
the basal meninges being involved late in the course of the disease. 
Aside from those forms occurring as a complication of other pathological 
conditions that lead to death before the meningitis has been fully devel- 
oped, it is the one most likely to kill the patient before distinct altera- 
tions have become evident. These cases are spoken of as foudroyant or 
fulminant. The disease is often accompanied by lesions in, other parts 
of the body, as petechiae in the skin, suppuration in the joints, multiple 
abscesses, endocarditis, degenerations of the myocardium, and suppura- 
tion of the labyrinth of the ear. 



928 



A TEXT-BOOK OF PATHOLOGY 



Associated Changes. — Besides the meninges of the brain, those of 
the cord are almost always involved, even in cases of tuberculous 
meningitis. The peculiarities of these conditions are described in the 
section on the spinal cord. Extension along the fold of pia mater that 
covers the choroid plexus is also common. The cerebrospinal fluid 
may be turbid, there is a moderate amount of lymph on the ependyma 
and over the surface of the plexus, and the latter may even contain 
small abscesses. Not infrequently in prolonged cases meningitic ad- 
hesions and occlusion of the aqueduct of Sylvius give rise to an acute 
hydrocephalus. 

The name serous meningitis has been applied to a symptom complex 
encountered in a variety of circumstances — juvenile gastro-enteritis, 
measles, pneumonia, otitis and others apparently only associated with 
great production of cerebrospinal fluid and without an increase, or 
pathological change at least, in the cell content. The pathology is 
vague because after death excessive fluid and pial injection are apt to 
occur without inflammation and these are all that are encountered in 
serous meningitis. 

Chronic leptomeningitis, a rare condition, may follow an acute 
attack or arise as a part of productive pachymeningitis or as a part of 
the chronic infections. It is commonly hypertrophic in form, leading to 
meningeal adhesions and involvement of the outer layers of the cerebral 
cortex in fibrous changes. The basilar form is perhaps the commonest, 
although a disseminated chronic meningomyelitis is usual in paresis. 

INFECTIOUS DISEASES 

Tuberculous meningitis is usually a manifestly secondary affection, 
although in children it may occasionally appear in connection with a few 
recent foci in other parts of the body. The bacilli ordinarily reach the 
meninges by the blood-vessels, particularly, in all probability, by the left 
carotid, from which situation they may spread along the base or to the 
vertex. Occasionally they seem to pass up the vertebral arteries, and may 
then affect the cerebellum more severely than the base of the cerebrum. 
Tuberculosis may also extend directly from tuberculous lesions of the 
skull or of the middle ear, and it has occasionally been observed to occur 
after traumatism. Other routes of infection, however, have been sug- 
gested, particularly, as in acute purulent meningitis, the organisms have 
been supposed to pass lip the posterior mediastinum, the retropharyn- 
geal areolar tissue, and thence into the cranial cavity. Mixed infection 
not infrequently occurs, and has been supposed to account for the 
purulent exudate. It is certain, however, that pure tuberculous menin- 
gitis may at times occasion the formation of pus. The organism that 
is most frequently found in connection with tubercle bacillus is the 
pneumococcus, and it may be found intimately associated, although 
it has been stated that the tubercle bacillus appears to predominate 
at the base of the brain and the pneumococcus in the exudate of the 
convexity. 

Pathological Anatomy. — In cases that die of pulmonary tuberculosis 
it is not uncommon to find, particularly in the pia upon the convex- 
ity, a number of small grayish nodules. These are not always appar- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



929 



ent upon superficial inspection, but by cutting through the cerebral 
hemisphere as far as the pia, and then stripping it away from the under 
surface of the membrane and holding the latter up to the light, they 
may readily be seen. In certain cases tubercle bacilli have been found 
when recognizable macroscopical lesions were entirely absent. Micro- 
scopical examination usually reveals a few masses of epithelioid cells 
and some slight perivascular round-cell infiltration. 

When the infection is more severe the tubercles are usually most 
numerous upon the base of the brain, particularly on either side of the 
carotid canal and in that part of the base just posterior to the dorsum 
sellse. Ordinarily the disease assumes the form of disseminated miliary 
tuberculosis. The tubercles are situated between the arachnoid and the 
pia, dften in the depths of the sulci. They vary in size up to 0.5 cm. 
in diameter, and often show slight cheesy degeneration in the center. 
The meninges are congested, and usually there is an exudate of inflam- 
matory liquid that contains flocculi of lymph, or is even seropurulent in 
character. Microscopical examination shows that the tubercles are 
composed of epithelioid cells, which occasionally seem to be dividing. 
Giant cells are also present, although perhaps not so frequently as in 
lesions in other parts of the body. There is usually round cell infiltra- 
tion about the vessels, and the latter are apt to be distended. This 
round-cell infiltration may also extend into the cortex of the brain, and 
the tubercles are often found in the latter situation. Tubercles may also 
exist in the choroid plexus. Sometimes, if the process has lasted for a 
long time and the tuberculous masses have increased in size, they may 
undergo cheesy degeneration and form irregular masses; these are 
usually found at the base of the brain, and often cause serious pressure 
upon the cranial nerves that they involve. 

Occasionally, when only a small number of bacilli have reached the 
meninges and have been deposited in one point, a single cheesy nodule 
may be found, particularly in one of the sulci, forming the meningeal 
tyroma, which sometimes attains a considerable size. In these less acute 
cases the exudate is considerable, and involves not only the subarach- 
noidal space, but also the ventricles of the brain, causing a condition 
that was formerly described as acute hydrocephalus which condition 
may cause the brain to swell and seem to fill the cranium completely, the 
convolutions appearing flattened. Numerous tubercles are found in 
the choroid plexus, and the ependyma "is covered with slight 
elevations resembling somewhat the appearance of cor villosum. These 
are usually found to consist of proliferated epithelial cells and of the 
subependymal neuroglia and fibrous tissue. Tuberculous infiltration 
of the brain substance is, however, very common. This may be either 
nothing more than an extension by continuity along the lymph-spaces 
and blood-vessels dipping from the pia or ependyma into the brain 
substance, and giving rise to small foci composed of epithelioid and 
giant cells surrounded by leukocytes, and perhaps exhibiting a slight 
degree of cheesy degeneration in the center; or else considerable areas 
of softening, which are perhaps caused by the formation of thrombi. 
These are most frequent in the corpus striatum and the crura, and 
appear as grayish-white or yellowish areas of softened and degenerated 

59 



930 



A TEXT-BOOK OF PATHOLOGY 



nervous tissue. Not infrequently, punctiform hemorrhages are found 
in the cortex about these areas of softening. In general, extension of 
the tuberculous process to the meninges of the cord occurs if the duration 
of the process is at all prolonged, but the vertebral canal is so much longer 
than the spinal cord that pressure symptoms rarely occur, and, as the 
irritation is slight, the cranial symptoms dominate the clinical course. 

Syphilis may occur in the form of gummatous infiltration and 
diffuse inflammations. In the former instances there are found flat- 
tened nodular thickenings of the arachnoid and pia, of grayish or pink- 
ish color, and tending to undergo necrotic change. The process begins on 
the inner surface of the arachnoid, or sometimes in the walls of the blood- 
vessels, and extends to the pia and cerebral substance on the one hand 
and to the dura on the other. In another form of syphilis there is diffuse 
infiltration or syphilitic leptomeningitis, causing considerable thicken- 
ing of the meninges. The characteristic of these conditions is the con- 




Fig. 460. — Gummatous meningoencephalitis (Ziegler). 



comitant obliterating endarteritis. The lesions of syphilis are like those 
of tuberculosis, but the definite rounded outline of the tubercle as against 
the irregularity and non-productively inflammatory nature of the gumma 
when combined with the microscopical picture of endarteritis and periar- 
teritis, and the characters of the giant cells, help in the diagnosis. The 
syphilitic giant cells do not have the typical peripheral or polar nuclei. 
Nevertheless the diagnosis is often exceedingly difficult. 

Chronic syphilitic leptomeningitis and meningo-encephalitis are 
occasionally met with. In these cases the membranes are thickened 
and fibrous, and secondary extension of the infiltration into the cerebral 
cortex occurs (Fig. 460) . 

The Pacchionian Bodies. — The most common, and clinically 
perhaps the least important, tumors of the arachnoid arise in the 
Pacchionian bodies. These are small granular masses or circumscribed 
nodules, chiefly along the edge of the superior longitudinal sinus but 
often extending a short distance laterally over the convex surface of 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



931 



the convolutions. Microscopically they consist of dense masses of 
fibrous tissue, covered by a layer of proliferated endothelial cells, which 
give them a concentric structure. Occasionally some calcareous 
nodules may be found in them. They may undergo active hyperplasia 
and grow outwardly, frequently eroding the skull, and giving rise to 
little pits upon the inner surface. 

Endotheliomata are most frequently found in the pia mater taking 
their origin from the endothelial groups in the arachnoid tufts or from the 
peri- vascular tissues in the latter case resembling this tumor in the dura. 
In the former case they present irregular alveoli, lined with cuboidal or 
round endothelial cells. These are not always arranged in a single 
layer, but may occasionally fill the alveolus, although this is not common, 




Fig. 461. — Perithelioma of meninges. 



and more frequently some have broken loose and lie free in the cavity. 
The cells often show karyokinetic changes, and occasionally alterations in 
shape, due to mutual pressure. These tumors resemble carcinomata 
closely, but the presence and proliferation of the epithelium-like cells 
in the stroma, such as occur in carcinoma, have not been observed 
(Fig. 461). They are soft gray or red, flat spreading masses. 

Sarcoma of the ordinary kinds may occur in the pia. Angiosarco- 
mata with and without degenerative changes are reported. Bone 
may be laid down in pial tumors (psammoma). Carcinoma does not 
occur, but tumors resembling it will be discussed under ependyma 
and ventricles. 

Cholesteatomata are terata, and have been observed in two related 
forms: those consisting exclusively of squamous epithelial cells, and 
those containing, in addition, various other epidermal structures, such 
as hairs or sebaceous glands. They are usually situated in or about 



932 



A TEXT-BOOK OF PATHOLOGY 



the median line of the calvarium; at the base of the brain; on the upper 
surface of the corpus callosum; or somewhere along the choroid plexuses. 
Those containiog hair are most frequently found near the cerebellum, 
growing either from the arachnoid, or, more rarely, from the outer sur- 
face of the dura. Those arising from the dura may occur upon the frontal 
or occipital bones, and often show calcareous infiltration, or even true 
osseous formation. 

Lipomata are rare. They are usually found in children, and always 
in the soft membranes, especially the pia mater. The most frequent 
seats are the upper surface of the corpus callosum and the corpora can- 
dicantia. According to Bostroem, they are probably epidermal in origin, 
nothing but the subcutaneous fatty tissue being left. 

Teratomata. — Growths of more distinctly teratoid character 
than the cholesteatomata, above described, are occasionally found. 
Chiari has described a case that grew from the lining membrane of the 
third ventricle in an infant that died at the age of seven weeks. It con- 
sisted of a medullary white mass and a number of serous cysts. The solid 
substance was composed of fetal brain substance in which were fissures 
lined with epithelium similar to that of the central canal of the cord, 
and ganglion-cells, retinal cells, skin-glands, and jelly of Wharton. Fi- 
brous and cartilaginous tissues were also present. 

The Brain 
development and anatomy 

Development. — (For convenience, the development of the cord is considered 
in this place with that of the brain.) The central nervous system commences as a 
shallow depression, that appears in front of the primitive streak in early embryologic 
existence. It is bounded on either side by ridges, known as the medullary folds. 
The groove gradually becomes deeper, and finally the two medullary folds unite, 
giving rise to the formation of the medullary canal. The canal is first formed in the 
portion that subsequently forms the cervical region of the spinal cord. Just beneath 
the medullary canal there is a cylindrical collection of cells, often with a small cavity 
in the center that forms anteriorly a shallow groove, the so-called notochord. Its 
function is unknown, and it eventually disappears during embryonic existence. 
The anterior extremity of the embryo continues to grow, and bends downward, 
forming the cephalic fold. In this part of the neural canal three dilatations occur— 
the primary vesicles of the brain; the posterior portion ultimately forms the spinal 
cord. 

The Cord. — At first the wall of the embryonal cord is composed of a single layer 
of cylindrical epithelial cells (spongioblasts), with nuclei at various distances from 
the central canal; these ultimately become the nuclei of the glia-cells. The central 
ends remain cylindrical; the peripheral ends become branched, forming the myelo- 
spongium, probably the antecedent of the neuroglia fibers, which, according to some 
investigations, become separated from the cells. At the age of about five weeks in 
the human embryo, certain cells, with a considerable amount of clear protoplasm, 
are found near the inner limiting membrane, the so-called germinal cells. Subse- 
quently other cells appear, probably derived from the germinal cells, as they are 
first found in the situations occupied by these, the so-called neuroblasts. These 
are distinguished by the appearance of a projection, pointing toward the periphery 
of the spinal cord, that grows out from the protoplasm and ultimately pierces the 
external limiting membrane to become an axis-cylinder. 

Just outside of the cord, probably from masses of epiblastic cells derived from 
its wall, the cells of the spinal ganglia appear. These are, at first, bipolar, one 
process extending into the spinal cord and the other peripherally, but ultimately 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



933 



the two processes unite at their commencement. The spinal cord at first com- 
pletely fills the spinal canal, but after the fourth month the vertebral column begins 
to grow somewhat more rapidly, and at birth the conus terminalis is opposite the 
third, and in the adult extends only to the lower end of the first, lumbar vertebra. 
The nerve-fibers are at first non-medullated, but later myelin-sheaths appear, first 
in certain parts of the posterior columns, and lastly in the pyramidal tracts, which 
often, at birth, are not yet entirely medullated. The membranes are derived from 
the mesoblast. 

The Brain. — The three primary vesicles from which the brain is developed con- 
tinue to grow, and the first is subdivided by a median constriction into two secondary 
vesicles, the prosencephalon and the thalamencephalon. From the former two 
lateral offshoots appear, which give rise to the cavities of the lateral ventricle, and 
from the walls of these are developed the cerebral hemispheres, the olfactory lobes, 
and the corpus callosum. The cavity of the second vesicle forms the third ventricle 
and from its walls grow the nervous structures of the eye, the optic thalami, and the 
pituitary and pineal bodies. The cavity of this vesicle (mesencephalon) forms 
the aqueduct of Sylvius, and from its walls grow the corpora quadrigemina and the 
crura. The posterior primary vesicle also becomes constricted, forming the epen- 
cephalon and the metencephalon. The two cavities, however, remain united and 
form the fourth ventricle. From the walls of the anterior portion are developed the 
cerebellum and the pons. From those of the posterior portion, the medulla oblongata. 

The ultimate shape of the brain, however, is largely determined by certain flexures 
and by the growth and extension of the axis-cylinders, which pass in various direc- 
tions and form the white matter, the greater bulk of the central nervous system. 
Differing from the cord, the growth of the brain exceeds that of its containing bony 
capsule. As a result the surface of the hemispheres is usually thrown into folds. 
The earliest of these appear during the third month, and are usually transverse to 
the axis of the brain, although not invariably. The lateral ventricles at this stage 
are very large, and the sulci project into their cavities as ridges. During the fourth 
month the deep fissures disappear, with the exception of three — the Sylvian, the 
calcarine, and the parieto-occipital fissures. The hippocampal fissure also appears 
about this time. The other permanent sulci appear about the end of the fifth month, 
the earliest being the fissure of Rolando; but many of the secondary fissures do not 
develop until after birth. 

The sympathetic nervous system is probably only an offshoot of the central 
nervous system. The cells first appear upon the spinal nerves, from which they 
wander, remaining connected with them by short branches, the rami communi- 
cantes. Some authorities, however, believe that the sympathetic system is devel- 
oped from the mesoblast. 

Anatomy. — The brain consists of the two cerebral hemispheres, the basal ganglia, 
the pons, the medulla, and the cerebellum. Its weight varies from 1200 to 1300 
grams in the adult female, and from 1300 to 1400 grams in the adult male. Its 
consistency at birth is very soft; in the adult it becomes somewhat firmer, but is 
always softer than the normal fiver. Its color varies from grayish white in the parts 
composed of medullated fibers to reddish gray in those composed chiefly of ganglion- 
cells. The cerebral hemispheres are separated by the superior longitudinal fissure, 
and united by the corpus callosum and the anterior commissure. They are joined 
to the pons by the crura. Their surfaces are rendered very irregular by the presence 
of numerous fissures or sulci, and are divided into the frontal, parietal, occipital, and 
temporosphenoidal regions. The important fissures are the Sylvian, the Rolandic, 
and the parieto-occipital on the external surface; the calloso-marginal, the calcarine, 
and the parieto-occipital on the medium surface. 

The hemispheres are composed essentially of an outer layer of gray matter, the 
cortex, containing ganglion-cells, and of fibers passing from these in various direc- 
tions and uniting them with other parts of the central nervous system. These may 
be divided into three main classes: the -projection fibers, passing between the cortex 
and the basal ganglia, or into the internal capsule; the transverse or commissural fibers, 
passing between the two hemispheres; and the association fibers, passing between 
different areas in the same hemisphere. The most important clinically of the pro- 
jection fibers are those which arise in the motor portion of the cortex, and pass first 
into the internal capsule, where they are grouped about the knee, thence through 



934 



A TEXT-BOOK OF PATHOLOGY 



the crura and the pons, to form ultimately the pyramids of the medulla. They 
decussate in the first cervical segment of the cord and form the pyramidal columns of 
the cord. The fibers of the optic radiation commence in the cortex about the cal- 
carine fissure and in the cuneate lobe, and pass forward to the pulvinar of the optic 
thalami. They are also associated with the external geniculate body and the ante- 
rior corpus quadrigeminus. From the pulvinar, the optic tracts pass around the 
crusta, then lie below and to the inner side of the internal capsules, and unite in 
front of the tuber cinereum to form the chiasm from which the optic nerves arise. 

The transverse or commissure fibers include those of the corpus callosum and of 
the anterior commissure. The fibers in the corpus callosum appear to correspond 
closely to those regions of the brain situated nearest to them. The anterior com- 
missure is composed of fibers uniting the temporosphenoidal lobes of the two 
hemispheres. 

The association fibers either connect adjacent lobes (fihrce propria), or unite dis- 
tant portions of the hemispheres (the long association fibers). 

In the substance of each hemisphere are found the lateral ventricles: two long, 
narrow, branching cavities, joined to the third ventricle by the foramen of Monro. 
Each contains a choroid plexus, and is normally lined with epithelium and contains 
clear cerebrospinal fluid. The anterior portion of the two ventricles is separated by 
the septum. A small double layer of epithelial cells fine and almost fill the cavity 
of the third ventricle. The basal ganglia of the brain are the lenticular nucleus, the 
caudate nucleus, forming together the corpus striatum, and lying on either side 
outside of the internal capsules, the optic thalamus, a large oval mass lying beneath 
the caudate nucleus. To the outer side of the lenticulate nucleus is a band of white 
fibers, known as the external capsule, that is separated from the cortex by a thin layer 
of pigmented cells, the claustrum. 

The third ventricle communicates with the fourth by a narrow canal, the aque- 
duct of Sylvius, which passes through the tegmentum of the crura. It is surrounded 
by a zone of gray matter, in which are found the nuclei of the oculomotor nerves. 
Above it are the four corpora quadrigemina, two pairs of rounded eminences with a 
white cortex and a gray center. The superior corpora, as has been already stated, 
are intimately connected with the optic tract. Just anterior to these bodies is the 
small pineal gland, situated above the posterior commissure. Externally to the 
crura on either side, continuous with the posterior portion of the thalamus, are the 
two geniculate bodies, separated by the optic tract. The optic thalami lie on either 
side of the third ventricle and just beneath the caudate nuclei; they are oval bodies 
containing numerous groups of nerve-cells, the anterior portion being called the ante- 
rior tubercle, and the posterior portion the pulvinar. 

The two great channels by which fibers pass to and from the cerebrum are the 
crura cerebri. These are divided by a narrow layer of dark-gray material, the sub- 
stantia nigra, composed of pigmented ganglion-cells, into the crusta or inferior por- 
tion, and the tegmentum or superior portion. A part of the cms is formed, as has 
already been stated, by the pyramidal tract. Sensory nerve-fibers are found in two 
groups in the tegmentum toward the outer edge, comprising the inferior and superior 
fillets. 

The two crura unite to form the pons, which is composed, vent rally, of bundles 
of motor fibers separated by the commissural fibers of the cerebellum, and dorsally, 
partly of the fibers of the fillet and partly of gray matter. Below the pons is found 
the medulla, which is really nothing but the upper portion of the spinal cord. Ante- 
riorly we find two well-defined bundles of motor fibers, the pyramids; just back of these 
the lower olives; and on the dorsal surface the nuclei of the tenth and twelfth nerves, 
and externally to them the nucleus gracilis and nucleus cuneatus, the terminations 
respectively of the columns of Goll and Burdach of the cord. The axis-cylinders 
of the cells that compose these nuclei pass toward the brain and form the fillets. On 
the outer surface of the medulla, near the dorsal surface, are the two restiform bodies, 
the continuations of the cerebellar peduncles. 

The cerebellum is composed of two lobes and the vermiform process. Upon 
cross-section it is seen to be composed of a great number of narrow gyri separated 
by deep ramifying sulci, each convolution being lined externally by medullated 
fibers, beneath which is a layer of ganglion-cells enclosing a center of medullated 
fibers. It is united to the cerebrum by the superior peduncles, which terminate in 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



935 



the nucleus ruber of the tegmentum. The middle peduncles form the transverse 
fibers in the pons, and the inferior peduncles pass into the restiform bodies of the 
medulla. Certain nuclei are found in the interior of the white substance, of which 
the most important is the dentate nucleus, analogous structurally to the olives of 
the medulla. 

The Neuron. — Histologically, the essential element of the nervous system is the 
neuron. This, in the sense of Waldeyer, comprises the nerve-cell, its protoplasmic 
processes (which are branched), and the axis-cylinder, or axone, which may be a 
single fiber giving off angular collaterals, or is extensively branched (Golgi cells). 
The cell-body consists of protoplasm without a distinct cell wall, and containing or 
not containing chromophilic bodies. According to Nissl, two groups of cells are thus 
formed, the somatochromes with, and the caryochromes without, these bodies. 
According to zoologists, these are respectively motor and sensory in function, but the 
cells of the spinal ganglia, which appear to be sensory, contain these granulations. 
Cells are spoken of as multipolar or bipolar, according to the number of processes 
that project from them. It is impossible to describe in this place all the varieties 
of cells and their distribution in the nerve substance. The neurons may be divided 
into endogenic, wholly within the central nervous system, and exogenic, partly in 
the peripheral nervous system. Each axis-cylinder terminates in a tuft of fibers that 
surround, without touching, some other ganglion-cell, or, if it extends to the periphery, 
terminates in a special sensory corpuscle or a muscle-plate. Upon emerging from a 
cell the axis-cylinder becomes surrounded by a sheath of myelin, while about several 
axones and their covering a fibrous coating, the sheath of Schwann, appears. 

Nerve-cells and fibers are supported by a special tissue, glia-cells and their inter- 
lacing fibrils. The cells are small, deeply staining, and of round or irregular shapes, 
beset with numerous delicate branches. In the white matter these cells are called 
"spider cells," and have stiff straight processes, while in the gray matter the branches 
are more irregular and are subdivided. There is beside these cells a small amount 
of ordinary connective tissue. 

Physiology of the Brain. — This subject can be touched upon only very briefly. The 
brain is the organ in which all the intellectual processes are performed, but it is as yet 
unknown how this is accomplished. A number of theories have been suggested, but 
none of them are based upon observed fact. We are better informed concerning the ori- 
gin of certain specific motor impulses in the brain, and the regions where stimuli from 
certain of the special sense organs are received. The motor region is situated in the 
two gyri on either side of the fissure of Rolando, and in the posterior portions of the 
three frontal gyri. In general, it can be said that the centers are arranged so that 
the cells sending fibers to the highest portion of the body — that is, the face, eyes, 
etc. — are situated in the lowest portion of the motor region; and the cells sending 
impulses to the lowest portion of the body — the feet, for instance — are situated in 
the highest portion of the motor region along the superior longitudinal fissure. 
This region has been mapped out by the aid of direct observation, not only upon the 
lower animals but upon human beings. Any irritation causes movement of the 
corresponding portion of the body, the movement being of a co-ordinated and not 
of an individual muscular type; that is to say, the stimulation of a center in this 
region causes contraction of a number of muscles, with the object of accomplishing 
some definite movement. The fibers of the motor region constitute the pyramidal 
tract, whose course has already been described. Irritative lesions of the motor cortex 
produce convulsive explosions, clonic in type, usually described as epileptic. If the 
lesions are sharply circumscribed, and the convulsions occur always in a certain defi- 
nite group of muscles, the condition is spoken of as Jacksonian epilepsy. Destructive 
lesions cause paralysis of a spastic type; that is to say, the lower motor neurons 
evidently suffice to maintain a condition of contractility in the muscles, which may 
be exalted either as a result of some irritation exerted by the degenerated central 
motor neurons, or because, under normal conditions, the central motor neurons 
exert an inhibitory or restraining action. We are still in ignorance concerning the 
localization of the sensory impulses. The effect of lesions in the upper portion of 
the parietal lobe in producing sensory forms of muscular inco-ordination has led 
to the supposition that the fibers conveying muscular sense terminate in this region. 
It is practically certain that the great majority of the sensory fibers terminate in the 
optic thalamus, from which other fibers proceed to the cortex; but as brain physio 1- 



936 



A TEXT-BOOK OF PATHOLOGY 



ogists are practically agreed that all the active intellectual processes are accomplished 
in the cortex, it is supposed that the thalamus is merely a situation in which some 
alteration or modification of the impulses received from the periphery occurs. Regard- 
ing the special senses, the visual impressions terminate in the cuneus. The auditory 
centers are situated in the superior temporosphenoidal convolutions, and the destruc- 
tion of these centers produces loss of understanding of sounds heard — that is to say, 
sensory aphasia. The centers for olfaction are situated in the uncinate gyri. Irri- 
tation of these regions has in some cases apparently given rise to subjective odors, 
usually disagreeable. They may occur as the aurae of epileptic attacks. The center 
for taste has not been located, although it is probably in this region. The func- 
tions of the remaining portions of the cortex are practically unknown. It is supposed 
that the intellectual processes are performed chiefly in the frontal lobes. At any 
rate, extensive lesions of these lobes have caused alterations in character — loss of the 
faculty of attention, more or less stupidity, and hebetude. Occasionally ataxia is 
present. The relation of pathological processes in the brain to insanity is not well 
determined. Lesions have, of course, been found in paretic dementia, in acute deli- 
rium, and in idiocy, but examination of the brain in cases of paranoia and melan- 
cholia has been practically negative. The functions of the other portions of the brain 
are not well determined. The basal ganglia are apparently merely stations in the 
paths of the fibers, chiefly those of sensory nature. The anterior corpora quadri- 
gemina have something to do with the fibers of the optic tract, and in them is prob- 
ably situated the center of the pupillary reflex to light. The external geniculate 
ganglia are apparently associated with the fibers conveying auditory impressions. 
The pons contains the ganglion-cells of the peripheral motor neurons of the eye- 
muscles, but is otherwise merely a pathway for various tracts of fibers. The medulla 
contains the ganglion-cells of the cranial nerves, and, in addition, all the tracts of 
fibers passing between the brain and cord. The functions of the cerebellum are not 
well known. There is no doubt that it has something to do with equilibration, but 
the lesions must be situated either in the vermis or bilaterally. 

POSTMORTEM DEGENERATIVE CONDITIONS 

It is important to be acquainted with the postmortem alterations that may take 
place in the nervous system, in order to avoid the confusion of such changes with 
those that have occurred as the result of disease. Little attention has been paid to 
the macroscopical changes, and they are not characteristic. Their degree depends 
upon the temperature at which the body has been kept after death, the nature of the 
disease that preceded death, and the period that elapsed before the tissues are 
removed. Ordinarily no changes will be noticed under thirty-six hours if the body 
is kept on ice. If kept at a temperature of about 16° C.(61° F.), the brain and cord 
will appear normal if removed within twenty-four hours. There is first softening of 
the nervous tissue that is general and not associated with pigmentation; the tissues 
may become so soft that it is almost impossible to remove them without injury. 
Later, there is often a considerable extravasation of blood-pigment around the 
vessels; and, finally, if putrefaction is advanced, the tissues become almost diffluent 
and light brown in color. 

Italian authors have studied methodically the microscopical changes. The nerve- 
cells swell, their protoplasmic processes break off, and there is a gradual loss of the 
staining power of the chromatin bodies; vacuoles appear in the protoplasm and the 
outline of the cell becomes irregular, and finally the chromatin substance completely 
disappears. The outlines of the nucleus become indistinct, it swells, and then con- 
tracts, with irregularity of the outline. It stains homogeneously, due to diffusion 
of the chromatin, and may contain small granules of hyaline material. Later it 
loses its staining power, and finally disappears completely. The nucleolus is the 
last structure to show alteration; it may swell slightly, become filled with vacuoles, and 
then breaks up into granular material and disappears. The protoplasmic processes 
do not exhibit varicosities, but apparently become more fragile, and are very apt to 
be broken off during staining. Changes may take place in the myelin-sheaths that, 
when studied by Marchi's method, are not greatly different from those seen in areas 
of softening — that is, small fatty granules appear along the course of the nerve-fiber. 
In postmortem lesions there is no perivascular round-cell infiltration; no compound 
granular cells can be found in the tissue; there are no signs of proliferation in the 
neuroglia, and the process is more general and uniform than is apt to be the case in 
morbid conditions. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



937 



CONGENITAL ABNORMALITIES 

The deformities of the brain are numerous and complicated. They 
may be divided roughly into those associated with alterations in the 
skull and those occurring within the cranial cavity. 

Acrania is a deformity characterized by absence of the skull. The 
membranes are usually preserved and form a sac filled with serum, on 
the inner surface of which small particles of nervous tissue may occa- 
sionally be found. More frequently the brain forms only a small mass 



/ * » ° • * ?' 0 

I - ': ■'. -•„■;'• ' 

' ' '<> ' 4 * i * ** * 6 * • * 




"t i. .... .^TT 





Fig. 462. — Meningo-encephaloma which grew in a meningocele into the nose. Note the 
cerebral, meningeal, and glial elements. 

at the upper portion of the spinal canal, lying on the basilar process 
of the occipital bone. Sometimes it appears as if the sac had ruptured 
or had never completely closed, for the membranes are collapsed and 
form upon the base of the skull a mass consisting of fibrous connective 
tissue and blood-vessels. Often in this case the encephalon is entirely 
absent, but the pons and medulla may be almost completely developed. 
The cranial nerves are present. 

Hemicrania is a condition in which more or less of one of the parietal 
bones, or of a portion of the frontal or temporal bone, has failed to 
develop. The corresponding portions upon the opposite side that have 
developed are usually hypoplastic. Ordinarily, anencephaly, or else 
partial development of the brain, is associated with these changes. 



938 



A TEXT-BOOK OF PATHOLOGY 



Cranioschisis is the name applied to imperfect closure of the skull 
along the middle line. This may be associated with rhachischisis in which 
case both skull and spine are cleft. The commonest situations for small 
fissures are in the frontal bone, in the region of the posterior fontanel, 
in the median line of the posterior portion of the occipital bone, and, more 
rarely in the region of the anterior fontanel or the sagittal suture or in 
the sphenoid bone. 

Fissures or other small defects usually occasion hernia of the brain, 
which is named encephalocele, and according to its situation anterior 
or posterior, frontal or occipital, superior, inferior, or lateral. If, instead 
of brain substance, only the membranes protrude through the fissure, 
the condition is known as meningocele. In these cases the cavity is 
filled with cerebrospinal fluid. Sometimes the under surface of the 
membrane is lined with nervous tissue, showing that it represents a 
dilatation of one of the primary cavities of the brain, corresponding to 
the condition found in spina bifida. These congenital herniae are prob- 
ably the result of fetal hydrocephalus, although it is possible that the 
chief cause is the imperfect development of the cranium. In cases in 
which the fissure is in the sphenoid bone, it is not uncommon to find, 
as an associated condition, cleft palate. Life is, of course, incompatible 
with extensive encephalocele. If it is small, the neck of the sac is some- 
times constricted, either spontaneously or as a result of surgical inter- 
ference, and recovery ensues. 

Cyclencephaly is a peculiar deformity in which there is failure 
of the anterior cerebral vesicle to develop. The frontal lobes remain 
fused and one rudimentary central eye develops (cyclopia). 

Abnormalities in Size. — The size of the brain is subject to con- 
siderable variation. 

Macrocephaly is the condition in which the brain is excessively 
large — that is, more than 1500 gm. This may be of two kinds. In 
the first, and perhaps less common form the brain is entirely normal 
in structure, the proportion between the various parts being maintained 
and the relation between the nervous tissue and the neuroglia not altered. 
In some instances the subjects possess unusual intelligence; in others 
this is not the case. The second form is enlargement of the brain with 
hyperplasia of the neurogliar tissue. This is not infrequently found in 
the so-called hypertrophic nodular gliosis or congenital sclerosis. In this 
condition the brain may be considerably enlarged, and the convolutions 
may be increased in size, although not abnormal in arrangement. On 
the other hand great disproportion may exist between the amount of glial 
and of nervous tissues, a condition found in some forms of idiocy. Mi- 
croscopically, the changes described in the section on sclerosis are 
discovered. A pseudo-enlargement of the brain is produced by hydroce- 
phalus. The weight of the brain, after the liquid has been removed from 
the cavities, is usually less than normal, although this is not always the 
case. 

Hypertrophy of the brain may be limited to certain parts. These 
are usually individual gyri, and are nearly always sclerotic. Sometimes 
only a portion of a convolution is thus affected, and produces a tumor 
like swelling. Hypertrophy of individual sections of the encephalon*, 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



939 



such as simple enlargement of the cerebellum, or of one of the cerebral 
hemispheres, does not appear to have been observed. 

Microcephaly is a condition in which the brain is much smaller than 
normal, as a result of defective growth or early fusion of the skull bones 
limiting the development of the encephalon, or else of disease, either in 
early life or later. In some instances the brains, aside from their small- 
ness, appear perfectly normal, and this diminution in size, within certain 
limits, is not incompatible with normal intelligence. Usually, however, 
there are sclerosis and decrease in size of some of the gyri. There are, 
of course, the associated changes usually found in sclerotic conditions. 

Hypoplasia of individual portions of the brain has been observed, 
particularly of the corpus callosum, the cerebral hemispheres, and the 
cerebellum. 

Hypoplasia of the cerebral hemispheres is usually due to some path- 
ological change, and will be discussed under sclerosis and porencephaly. 

The congenital absence, either total or partial, of the corpus callo- 
sum has been observed in a number of cases. It may occur in brains 
otherwise normal, but is usually associated with microcephaly or other 
profound structural changes. In the cases in which no other lesions 
exist the intelligence may be normal, but in the great majority of instances 
the patients are idiots. The appearance of the brain is quite character- 
istic. As soon as it is removed the hemispheres fall widely apart, showing 
the third ventricle covered with a delicate layer of pia mater. The inner 
surfaces of both hemispheres are divided by numerous fissures and appear 
atypical. In cases of marked hydrocephalus the corpus callosum is 
extremely thin, and may be torn during the removal of the brain, and this 
may possibly be mistaken for congenital absence. A careful examina- 
tion, however, will usually reveal the true state of affairs. 

Hypoplasia of the cerebellum, or even total absence of one or both 
hemispheres, has been occasionally observed. It is nearly always as- 
sociated with sclerosis. A collection of cerebrospinal fluid in part sup- 
plies the place of the absent organ. The cerebellum may be of normal 
shape, and even microscopically show no changes other than diminution 
in size. More commonly, however, the changes are asymmetrical, one 
lobe being markedly smaller than the other, and perhaps reduced even 
to a small papilla. There are often sclerotic changes, with marked atrophy 
of the cortex and disappearance of many of the medullated fibers. 
The corpora quadrigemina may also be altered, but this is not invari- 
ably the case. 

Other changes of unknown significance that have been described are 
abnormal arrangement of the convolutions. Of these the most important 
is the presence of annectant gyri across the Rolandic fissure, or the absence 
of annectant gyri in the parieto-occipital fissure. It does not appear, 
however, although the claim has been frequently made, that these 
changes are in any way associated with intellectual pecularities. Bun- 
dles of nerve-fibers, taking an abnormal course, have occasionally been 
found in the pons and medulla. These seem to be produced by premature 
decussation of portions of the pyramidal tract, and are of no clinical 
significance. 



940 



A TEXT-BOOK OF PATHOLOGY 



Anencephaly, or total absence of brain, is a congenital lesion 
usually associated with acrania. Sometimes it is associated with total 
absence of the spinal cord; in other cases a portion of the pons, medulla, 
and the cord are still present, although much smaller than normal. The 
cranial nerves are usually present, and the eyes, in particular, are nearly 
always perfectly developed. The lesion is, of course, incompatible 
with life, although when the medulla is present a few respirations may 
take place after birth. The appearance of the monsters is very charac- 
teristic. From the orbital ridge of the frontal bone the skull slopes in 
almost a direct line to the neck, making the face and eyes unusually promi- 
nent — the so-called frog-face. Frequently other deformities are also 
present. 

Porencephaly is a condition characterized by the absence of a 
greater or less amount of the substance of one or both of the cerebral 
hemispheres, leading to the formation of a cavity or cavities filled with 
cerebrospinal fluid. 

Etiology. — The cause of porencephaly is not definitely known. As 
Von Kahlden remarks, the similarity of the lesions in typical cases is 
such that it seems reasonable to accept a uniform etiology. Kundrat 
believed that the lesions were due to anemic infarction, as a result of 
occlusion of the Sylvian arteries. Von Kahlden, however, believes 
that it is the result of some disturbance in a development of the brain, 
and bases his opinion upon the symmetry of the lesions and their pecu- 
liar situation. Other authors have suggested an inflammatory origin 
of the process, because of the adhesions between the membranes. Some 
cases seem to be due to a failure of blood-supply to the affected part, 
either by malformation of the vascular channels or endarteritis. A 

certain number of cases certainly de- 
velop after birth; these may be due to 
injury, such as might be produced by 
instrumental delivery, or by blows upon 
the skull, or by embolic or inflammatory 
processes. 

Pathological Anatomy. — Von Kahlden 
has divided a large series of reported 
cases into two classes: the typical and 
the atypical. The former class com- 
prises about two-thirds of all the cases, 
and is characterized by the presence of a 
funnel-like cavity in the motor region 
of the brain, usually bilateral, although 
Fig. 463.— Porencephaly (case of unequal, that extends from the sub- 
Dr. J. h. Lloyd). arachnoid space to the cavity of the 

ventricle (Fig. 463). Frequently this 
condition is associated with imperfect development or exposure of the 
island of Reil. In the atypical form the lesions are exceedingly various; 
they may be found in any part of the cerebral hemispheres ; the shape of the 
cavity may be either a shallow depression or a deeper loss of substance. 
Often — in fact, usually — there is no communication between the cavity 
and the ventricle. These varieties may even be found in the cerebellum, 




\ 

DISEASES OF THE BRAIN AND ITS MEMBRANES 



941 



and perhaps are most frequent in the lateral lobes at the point where they 
unite with the vermiform process. Cases have also been recorded with 
cavity formation in the base of the brain, communicating sometimes with 
one of the horns of the lateral ventricles. A sort of cystic formation 
has been described, in which multiple cavities, not communicating with 
either the ventricle or subarachnoid space, have been found in the sub- 
stance of the brain. The macroscopical changes observed in the typical 
form are as follows: Ordinarily a distinct depression is noticed in the 
dura after the skull has been removed; when this region is more carefully 
examined it is found that the dura may or may not be adherent to the 
arachnoid which covers the cavity. The pia usually dips into and covers 
the excavation, and may be continuous with the ependyma of the ventri- 
cle. The adjacent convolutions of the brain are arranged in a somewhat 
radiate manner and turn down into the cavity, although this is not in- 
variably the case, for they sometimes may appear as if simply cut off, 
being otherwise normally arranged. Associated changes in the brain are 
microgyria; proliferation of the neuroglia tissue, and perhaps also of the 
connective tissue; atrophy of the nerve-cells in the cortex, particularly 
of the large pyramidal cells ; and more or less complete destruction of the 
nerve-fibers in the region adjacent to the defect. The spinal cord usually 
exhibits a secondary degeneration in the pyramidal columns; this how- 
ever, is not always the case, for sometimes it appears that one or both 
pyramidal columns have failed entirely to develop, giving rise to a con- 
dition of micromyelia. Other parts of the brain appear to be rarely 
affected in the typical form of the condition. When the lesion is situated 
in any other part than the central region, corresponding secondary de- 
generations may, of course, occur. 

GENERAL PATHOLOGIC ANATOMY OF THE NERVOUS SYSTEM 

The pathology of the nervous system differs from that of the other 
organs of the body chiefly in the fact that the special structures of which 
the nervous tissue is composed have no close analogies to the epithelial 
and connective tissues. It is desirable, therefore, to discuss first the 
general changes occurring in the nerve-cells, nerve-fibers, and the neuroglia. 

The Nerve -cell 

On account of their characteristic appearance and sharply differ- 
entiated structure, the cells of the anterior cornua of the spinal cord 
have been most carefully studied, and it is necessary, therefore, that we 
should give a brief description of their anatomy. The appearance 
depends largely upon the method of staining employed. By the Golgi 
method the cell appears as an irregular body, from which come a number 
of thick processes that rapidly divide and subdivide until they appear 
as a maze of independent delicate branches, dendrites, upon either side 
of which can be seen minute projections, the so-called gemmules ; from 
one portion of this cell a fine process arises that is of uniform width, the 
neuraxon. At regular intervals this gives off the so-called collaterals, 
delicate branches that spring from it at right angles and have a different 
course. By this method 'other ganglion-cells in the nervous system have 
also been carefully studied and show numerous variations in type, the 



942 



A TEXT-BOOK OF PATHOLOGY 



most important being in the number and complexity of the protoplasmic 
processes, and the division or even excessive branching of the neuraxon. 
The morbid changes that can be observed by the application of this 
stain are but few, since it appears that the pathological cells soon lose 
their power of impregnation. 

Apathy and Bethe, by the employment of certain exceedingly com- 
plex staining methods, claimed to have discovered that the nerve-cells 
are really nothing but stations in the paths of certain delicate fibrilla, 
called the neuro-fibrils, that pass from one cell to another, not being limited 
even to the ganglion-cells, but also passing through the neuroglia cells. 
They therefore believed, and Nissl has agreed with them, that these 
fibrils are the real functioning elements in the central nervous system, and 
that the ganglion-cells have probably only some nutritive influence. 

The alterations of the dendrites are essentially of two kinds: first, 
the appearance of varicosities upon the protoplasmic processes in their 
thicker branches ; second, the disappearance of the gemmules from the termi- 
nal filaments. Such alterations have been seen in chorea, in general 
paresis, in alcoholism, and other forms of poisoning. Sailer found very 
marked changes of this character in the spinal cords of guinea-pigs killed 
with tetanus toxin, and Steele described a varicosity upon the axis-cylinder 
in the cortical cell in an animal killed by diphtheria toxin. Lenhossek 
appears to regard the varicosities of the protoplasmic processes as the 
result of an accumulation of the chromophilic bodies, and Kolliker states 
that they are merely artefacts, a view held by most zoologists. 

In 1885 Nissl described a method for staining the nerve-cells which, 
on account of its differentiation of the structures of the protoplasm, 
and the possibility that by it cells in any stage of degeneration may be 
stained, has yielded most valuable results. It consists essentially of 
staining tissue, hardened in alcohol, by one of the basic anilin-stains, 
such as thionin or methylene blue. The cells of the anterior cornua 
show the irregular outline and the numerous protoplasmic processes 
as before. Throughout the protoplasm are small, irregular bodies, 
sometimes vacuolated, that take the basic stain intensely. They are 
arranged somewhat concentrically around the nucleus, but at the points 
where the protoplasmic processes come off become spindle shaped and 
turn into them, and are also found in the processes as spindles. Between 
these bodies the cytoplasm refuses to take the stain, and is called the 
achromatic substance. Nissl and some others believe that it has a delicate 
fibrillar structure, and strands can be brought out, by the Bielschowsky 
method, running across the protoplasm into the dendrites and axones. 
A cup-shaped portion of the protoplasm remains clear, and is usually 
rather sharply delimited from the remainder of the cell. From this 
extends a long, faintly staining, undifferentiated neuraxon. The nucleus 
does not stain, but remains as a clear space near the center of the cell, 
containing a round deeply staining and usually vacuolated nucleolus, 
surrounded by a membrane with irregular thickenings (Fig. 464) . It has 
been claimed (Kronthal) that these so-called chromophilic bodies do not 
exist in the living cell, but are the products of disintegration. The 
course of pathological changes appears to be somewhat as follows: 
The granules become first very irregular in distribution and somewhat 



DISEASES OF THE BRAIN AND ITS MEMBRANES 943 

finer, so that the concentric arrangement is no longer distinct. They may 
then diminish considerably in number, so that the cell as a whole appears 
very much paler; finally, the protoplasm may become entirely clear, a 
small amount of basophilic substance only remaining that is collected in 
irregular masses around the nucleus. This also may disappear, and the 
cell remain as an irregular, faintly and diffusely stained mass in the 
midst of the tissue. When stained by silver method the fibres will be 
found apparently dissolved about the nucleus while traces of them re- 
main at the periphery and in the roots of dendrites and axones. This 
series of changes is by no means the only one that has been described. 
Occasionally the chromophilic granules seem to dissolve, although their 
capacity for staining is unimpaired, resulting in deeply and diffusely 
staining cells without any apparent structure, excepting the vesicle 
in the situation of the nucleus (pyknomorphous state). Nissl regards 
these as artefacts, and it is true that they are frequently found in tissues 
supposed to be healthy. It must not be forgotten that they are always 




Fig. 464. — -Normal and degenerated nerve-cells of Fig. 465. — Degenerated nerve-cells 
the anterior cornua of the spinal cord; X 600. in the neighborhood of a collection of 

pus; the granular appearance is due 
to an excess of pigment; X 600 
(case of Lloyd and Sailer) . 

far more numerous in diseased tissues or in the neighborhood of focal 
lesions. We have observed some singularly beautiful examples of this 
change in the brain of a guinea-pig killed by anthrax, in which the micro- 
organisms were found in the nervous tissue. The solution, with or 
without loss of staining power, corresponds very closely to the changes 
observed in the chromatin in karyolysis, and may be very properly 
described as a sort of chromolysis. In other cases chromophilic bodies 
may collect in diffuse, irregular masses in one or more parts of the proto- 
plasm, a change which has been observed in the spinal cells of cases of 
tetanus. 

Still another form is the coalescence of the chromophilic bodies, so 
that each individual one appears larger; their number is less, and they 
still maintain a rather regular arrangement in the protoplasm. These 
masses may then further coalesce, giving rise to the appearance just 
previously described, or may break up, causing a uniform granulation of 
the cell, or they may disappear. 



944 



A TEXT-BOOK OF PATHOLOGY 



Another change that frequently occurs in pathological cells is vacuo- 
Uzation. It is possible that a few vacuoles of small size may be the result 
of the hardening processes. In some cases, however, this alteration is 
very extensive, the vacuoles reaching 70 \x in diameter. They appear to 
be filled with a liquid, possibly lymph, that may undergo slight coagula- 
tion-necrosis; at least fibrillse, that may be fibrin, have been observed. 
The cells often acquire extraordinary appearances. Indeed, it may look 
as if the pericellular space was enormously dilated, and that bands of 
protoplasm extended from it to the surrounding neuroglia. The arrange- 
ment of the vacuoles is always exceedingly irregular, and if more than one 
be present, as is usually the case, the vacuoles vary greatly in size. 

Sometimes, instead of the vacuoles, there may be found in the cells 
masses of some substance that differs from the protoplasm. These 
are usually homogeneous irregular masses that take the acid stain, and 
have been described as " colloid" in nature, using the word in the sense 
given to it by von Recklinghausen. The true nature of this change, 
however, is not very clearly understood. Sometimes the vacuoles 
appear to be replaced by clefts distributed irregularly in the proto- 
plasm. 

In nearly all degenerated cells there is accumulation of a peculiar 
cellular pigment. This may be fatty in nature, as it stains black with 
osmic acid. In some cases it seems to increase pari passu with the dis- 
appearance of the chromophilic bodies, so that ultimately the cell appears 
as an irregular mass filled with this yellowish-brown pigment. It occurs 
normally in old age, is found in the cells of the substantia nigra of the 
crura, is an almost invariable accompaniment of those diseases in which a 
sort of early senility appears to occur, such as general paralysis, and is 
rarely found in cells undergoing very acute degeneration. Another form 
of pigment giving the iron reactions occurs in certain pathological states. 
McCarthy has reported its occurrence in the brain of a rabbit killed by 
snake-venom. 

The changes of the nuclei first appear in the nucleolus; this, as has 
been said, normally contains one or two vacuoles. In degenerative 
processes it begins to swell, and more vacuoles develop, so that finalty 
it presents the appearance that has been likened to the morula stage of 
the ovum. Ultimately, as the degeneration progresses, it may grow 
fainter and disappear entirely. Clumps of chromatin are often observed 
at the periphery of the nucleolus, and occasionally ray-like fibers pro- 
ject from them into the nucleus; accessory nuclei are also often present. 
Two or more nucleoli have also been observed, but it is doubtful if this 
is a morbid change, although Berkeley contends that it is an invariable 
sign of irritation. 

The nucleus itself exhibits a variety of changes. Stained with 
hematoxylin, it shows a delicate chromatin reticulum, and this may 
exhibit, in the ordinary forms of degeneration, changes that are found 
in other cells in the process of karyolysis; occasionally the chromatin 
collects in a diffuse, irregular mass about the nucleolus. In various 
forms of degeneration the nucleus seems to be stimulated, and shows 
karyokinetic figures, or may even divide completely, so that two nuclei 
are found in the same cell. This, however, is not necessarily a degen- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



945 



erative change, because similar appearances are found in embryonal 
and in lacerated nerve tissue. Perhaps the most important nuclear 
change, and one that is most certainly pathological in nature, is the dis- 
location of the nucleus. It may be found at the periphery of the cell, or 
even protruding from it, as if to be expelled. It has been said that the 
nucleus can disappear from the cell when it does not present marked 
degenerative changes; it must be remembered, however, that the large 
diameter of the multipolar cell renders it possible with a good micro- 
tome to make a number of sections through a single cell, and it is very 
likely that these conditions are due simply to sections beyond the plane 
of the nucleus. In the most advanced types of degeneration the nucleus 
certainly disappears completely. 

Changes may also take place in the ceil as a whole. In the process 
of degeneration its outline usually becomes irregular and angular. The 
cell appears to be smaller, and often the pericellular space is very obvious. 
In many cases, however, this is an artefact, produced by the hardening 
fluid, and although it may be also the result of some morbid process it is 
impossible to give it any value as such. In the early stages of degenera- 
tion the protoplasmic processes may be unimpaired. Varicosities, such 
as shown by the impregnation, are rarely observed by the Nissl method. 
One of us has, however, seen them in the nerve-cells of the cord of a 
guinea-pig killed by tetanus. Tortuosity of the protoplasmic processes 
is very common, particularly in chronic conditions, such as sclerosis. 
It is impossible to stain the terminal ends by the Nissl method, and the 
changes in the gemmules cannot therefore be recognized. Sometimes the 
processes become friable, break off, and disappear completely, leaving 
the cells with a rounded outline. Finally, dislocation in the arrangement 
of the pyramidal cells of the cortex has been observed, particularly in 
cases of sclerosis of the brain, and it is probable that it occurs in all parts 
of the nervous system, although when the normal arrangement is irregular 
it is impossible to estimate its extent. 

The functions of the different portions of the nerve-cell are but 
imperfectly known. The neuraxon conveys impulses from the cells to 
the periphery, or transfers them in some as yet inexplicable manner in 
a variety of directions along the collaterals. The cell body has a dis- 
tinct trophic influence over the neuraxon, and when this is removed, 
either by destruction of the cell or by the division of the neuraxon, the 
peripheral portion of the latter rapidly degenerates. On the other 
hand, the experiments of Goldscheider, Flateau, and Nissl have shown 
that the neuraxon exerts at least a temporary influence over the nerve- 
cell, and when it is destroyed in any way pathological changes invariably 
occur. There are many theories concerning the function of the nucleus, 
but no more is really known about it in the nerve-cell than in any other 
cell. It is concerned in active division, but this is apparently an exceed- 
ingly rare occurrence in nerve-cells. The protoplasmic processes have 
been regarded as nutritive or as centripetal organs. Lenhossek has sug- 
gested that the long axis-cylinders that convey impulses to the cells of the 
spinal ganglia are only a modified protoplasmic process. If this is so, it 
would be sufficient proof that they have an active function. The fact 
that the axis-cylinders of other cells terminate in arborization about the 

60 



946 



A TEXT-BOOK OF PATHOLOGY 



dendritic processes, the cells forming the next link in the chain, is also a 
proof that even the short dendrites receive impulses. The fact that a 
single particularly thick dendrite may almost always be observed passing 
to the nearest blood-vessel indicates that they possess also some nutri- 
tive function, and that their extensive arborization is partly for the 
purpose of exposing as great a surface as possible to the nutritive fluid 
in which the cell is bathed. Concerning the pathological physiology of 
the nerve-cells we have at present little information, although certain 
definite changes have been described in cells that have been exhausted 
by excessive stimulation. What changes occur in the cell preceding 
the production of energy have not yet been determined. 

The nerve=fibers represent the extension in fiber form of the achro- 
matic part of the cellular protoplasm and, depending upon their later 
covering, are of two kinds, the medullated and the non-medulla ted. 
Non-medullated nerve-fibers consist of the axis-cylinder alone. They 
are found in the olfactory nerve and in the sympathetic nervous system, 
and when they undergo degeneration exhibit swelling and varicosities, 
and ultimately break down into a granular detritus. Non-medullated 
nerve-fibers may also be provided with a sheath, the neurilemma; such 
fibers are found in some of the cerebrospinal nerves. Medullated nerve- 
fibers may consist only of the myelin substance and the axis-cylinder — 
that is, the neurilemma is absent; such fibers are found in the central 
nervous system. Ordinarily, they consist of the neurilemma, the myelin 
substance, and the axis-cylinder; such fibers are found in the central 
nervous system and in the peripheral nerves. These fibers may branch, 
either giving off collaterals in their course or forming more or less complex 
aborizations at their terminations. The axis-cylinder usually exhibits a 
somewhat fibrillar structure. The myelin material resembles fat and has 
a high refractive index. It does not extend the whole length of the fibers, 
but at rather regular intervals is absent (nodes of Ranvier). These 
points are perhaps for the purpose of providing access for nutriment to the 
nerve-fiber. Upon the inner surface of 'the neurilemma are found a few 
oval nuclei surrounded by protoplasm. 

The function of the nerve-fibers is comparatively simple. Impulses 
are conveyed by the axis cylinder, the neurilemma and the myelin 
substances apparently serving for protection and perhaps nutriment. 
It was formerly supposed that the myelin acted as an insulating mate- 
rial; but the fact that non-medullated fibers exist shows that in some 
cases at least it is unnecessary for this purpose. 

The earliest evidence of degeneration in the nerve-fibers is the 
appearance of granules in the myelin-sheath. These soon run together 
and form droplets that give all the reactions typical of fat. Such a 
fiber, examined microscopically in longitudinal section, exhibits these 
droplets arranged irregularly along its course, giving rise to a somewhat 
beaded appearance. The next change is usually found in the axis- 
cylinder. This may swell and become extraordinarily varicose, so 
that indeed it loses all resemblance to a nerve-fiber. Instead of being 
fibrillar, it has an irregular granular appearance, and may contain here 
and there minute droplets of fat, or the fiber may shrink and become 
granular, and ultimately disappear, nothing remaining to indicate its 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



947 



previous existence excepting a mass of delicate granular detritus. These 
changes may be brought about either by the destruction of the ganglion- 
cell from which the axis-cylinder forming the fiber arises, or by separation 
of the fiber from its ganglion-cell, or by injurious agencies acting locally 
upon the nerve-fiber. The second form of degeneration — that is, taking 
place in the peripheral portion of the cut nerve — is known as Wallerian. 
Changes in the proximal end also occur, but rarely extend further than the 
first node of Ranvier. When a nerve has been divided the earliest change 
is found on either side of the point of division, and consists in fragmenta- 
tion of the myelin. About the third day fat-droplets appear in the mye- 
lin; there is some swelling of the axis-cylinder, and often proliferation of 
the nuclei in the neurilemma may be observed. As the myelin breaks 
down into a fatty detritus, it is gradually absorbed by the compound 
granular cells, which appear all along the course of the nerve-fiber, and 
at the end of three or four months it has entirely disappeared. During 
this period the neuroglia is undergoing' proliferation; at first there is 
a slight increase in the number of neuroglia cells; later, the prolifera- 
tion of fibers preponderates, and finally, the degenerated area 
is occupied by a thick mass of coarse' fibers that usually undergo slight 
contraction. The proliferation of the cells ceases about the time that the 
fibers have become completely degenerated. The subsequent prolifera- 
tion, if any, occurs only in the neuroglia fibers. The central portion of 
the separated fiber will, after a long interval, also degenerate; this is 
possibly due to functional inactivity, and appears to be more of the nature 
of an atrophy. Thus in amputations that have occurred in early life, the 
anterior roots, forming the nerves that supply the amputated limb, be- 
come smaller and contain fewer fibers, and there is ultimately some 
degeneration in their ganglion-cells of the anterior horns. Regeneration 
of nervous tissue occurs in the invertebrates and possibly among fishes 
and reptiles, although this is very uncertain. Regeneration of nerve- 
fibers in the peripheral nervous system occurs in all the higher animals, 
including man. After the nerve-trunk has been cut, the peripheral ends 
of the axis-cylinder of the central portion of the nerve become swollen and 
split up into very fine fibrillse. These grow in various directions, and, if. 
they unite with the distal portion of the nerve, will serve it as a skeleton, 
and one of them, at least, will grow toward the periphery, ultimately 
forming new nerve-fibers. These changes occur in both sensory and 
motor fibers. (See section upon the Regeneration of the Peripheral 
Nerves.) 

Nerve-cell and fiber degenerations may be produced by endogenous 
toxins, such as those of uremia, or by the poisons of bacteria and proto- 
zoal diseases, and from exogenous poisons, such as lead and alcohol. 
It is probable that the changes vary with the cause in the early stages, 
but they are so seldom seen that it is difficult to be certain. The changes 
seem to take the form of chromatolysis and fatty degeneration in nerve- 
cells and granular or fatty change in the axis-cylinder and myelin-sheath. 

Disturbance of nutrition, either acting locally upon a terminal part 
of a nerve or by affecting the central cell, will cause degeneration, usually 
tending to travel toward the controlling ganglion cell. Fatigue may 
cause degeneration of a nerve, but it seems that this is due to some 



948 



A TEXT-BOOK OF PATHOLOGY 



primary change in the ganglion cell ; the alterations suggested consist in 
a condensation of the protoplasm, with a tendency to diffuse staining, 
and a reduction in the size of nucleus and cell as a whole. 

The neuroglia of the nervous system may proliferate or undergo 
softening, the former change producing various forms of sclerosis or 
gliosis. 'Sclerosis of the brain may be either diffuse or circumscribed, 
and the latter is again subdivided into the hypertrophic and atrophic 
forms. 

Diffuse sclerosis of the brain never involves all parts equally. To a 
certain extent it is normal in old age, and is usually found to be limited 
to the most superficial portion of the cortex beneath the pia, or else to 
the layer of the gray substance adjacent to the white matter. The 
neuroglia tissue in either situation appears to be composed of rather 
coarser fibers than normally, forming either wavy bands or a coarse 
network. Macroscopically the brains exhibit only slight alteration. 
The consistency may, on account of other senile changes, be even slightly 
reduced; the gray matter is usually narrower than normal; the pia 
mater is generally firmly adherent, but not invariably. This condition 
sometimes occurs in connection with other diseases, as epilepsy, or may 
be congenital. 

Disseminated sclerosis is sometimes only slight in extent. It may 
occur in the brains of epileptics, of criminals, of old persons, and of 
idiots. Small sclerotic foci are usually found at the junction of the 
gray and white matter, more often in the former than in the latter. 
The neuroglia tissue forms a coarse, irregular network; as a rule, it is 
unusually vascular and without any or only a few true nervous ele- 
ments. These areas may be detected by the naked eye, when large 
enough, by the fact that they are paler than the surrounding tissue and 
often slightly sunken. If the process is more extensive and involves 
the whole thickness of one or more gyri, it gives rise either to an atrophic 
or hypertrophic form, or both may coexist in the same brain. The 
external appearance in these cases is characteristic and cannot be mis- 
taken for any other process. 

In the atrophic form the gyri are reduced perhaps to the thickness 
of a lead-pencil, they are pale, firm, slightly granular upon the surface 
and the pia mater may occasionally be slightly adherent. Section 
through one of these convolutions shows that the cortex is considerably 
thinner and has a tendency to retract. The white substance is also 
involved, but apparently less severely. The extent of the process is 
very variable, one or two convolutions only being affected, or perhaps, 
as in several reported cases of epilepsy, only the cornua ammonis. Some- 
times a number of convolutions are affected, and in the majority of 
these cases there is some tendency to an irregularly symmetrical dis- 
tribution. Microscopically these lesions show marked hyperplasia 
of the neuroglia tissue — that is, increased number of neuroglia cells 
and coarseness of the neuroglia fibers, which form coarser meshes than 
normal. Many of the neuroglia cells are swollen, the nuclei are enlarged, 
pale, and the outlines of the cells are irregular. The nervous elements 
may appear to be more thickly placed and somewhat irregularly dis- 
tributed, and the protoplasmic processes of the ganglion-cells are often 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



949 



tortuous. More frequently they are considerably diminished in number 
or else entirely absent. The myelinated fibers are always decreased, 
particularly the tangential fibers of the cortex. The vessels are more 
numerous than usual and often show wide perivascular spaces filled with 
fibrous tissue. In the most advanced areas, however, the vessels may 
be entirely absent. Corpora amylacea or other products of nerve 
degeneration are sometimes found. These changes are found in epi- 
lepsy and idiocy, and when the lesions occur in the motor region are 
always associated with motor disturbances. 

In the hypertrophic nodular form, the brain, as a whole, is usually 
somewhat enlarged, and nodules are found in the cerebral cortex that 
project from the surface and are much harder than the surrounding 
substance. The larger ones are often slightly umbilicated. The 
surface of these nodules is often granular. The microscopical changes 
are similar to those found in atrophic sclerosis, with the exception that 
the excess of neuroglia tissue is much more pronounced. In these 
brains there are often sclerotic areas beneath the ependyma of the 
ventricles, the lateral ventricles being more frequently affected than 
the third or fourth. These nodules are small, round, and very hard. 
Microscopically, they are found to consist of neuroglia fibers arranged 
in a somewhat concentric manner. They may be vascular or entirely 
deprived of blood-vessels, and sometimes contain chalky deposits or 
masses of hyaloid material. As in all destructive lesions of the central 
nervous system, secondary degenerations may occur, but they are far 
less common than would be suspected from the apparent extent of the 
degenerative processes. These forms of congenital sclerosis probably 
commence after the seventh month of fetal life, because, as Kundrat has 
pointed out, the arrangement of the convolutions is rarely disturbed. 
They have been ascribed to syphilis, to inflammatory change, to conges- 
tion of the lymphatic system, and to something akin to tumor formation. 
The absence of round-cell infiltration, and the fact that the pia is rarely 
adherent, even when the sclerosis takes place in the most superficial 
layers of the cortex, would seem to exclude inflammatory causation. 
Neurogliar proliferation occurs about gumma, but there is no ground 
for believing that all other forms are also due to syphilis. The dilata- 
tion of the perivascular spaces is favorable to the theory of congestion 
of the lymphatic system. This, however, is probably secondary. It is 
no explanation for this process to say it belongs to the tumors, but at 
present it appears impossible to give a more satisfactory etiology. 
Softening of the neuroglia is a part of all processes of softening in the 
brain, which are described in connection with thrombosis and embolism. 

THE BLOOD-VESSELS 

The arteries of the brain may be divided into two groups, those 
nourishing the cortex and those nourishing the basal ganglia. The 
former are the ramifications of the terminal branches of the circle of 
Willis, after they spread themselves over the pia, from which membrane 
they penetrate the cortex. The basal ganglia receive large straight 
vessels from the circle. All these blood channels terminate in end 
arteries, that is little or no anastomosis exists. Within the brain sub- 



950 



A TEXT-BOOK OF PATHOLOGY 



stances the small vessels are surrounded by rather wide lymph spaces 
and indeed all through the nervous system there is no great tissue support 
given to them. Their walls are relatively thin but are copiously supplied 
with elastic tissue particularly in the outer media. 

Arteriosclerosis. — The changes that occur in the arteries are those 
ordinarily occurring in the vessels of the other parts of the body, atheroma 
of the arteries of the base of the brain being perhaps more frequent 
than of the arteries of other organs. These atheromatous changes 
usually lead to calcareous infiltration, and in old age often the entire 
circle of Willis is composed of typical pipe-stem arteries. When the 
process is less extensive, the calcareous infiltration is most apt to affect 
the two internal carotids, the middle cerebrals, and the basilar artery. 

Hyaline degeneration may also occur. It is of two kinds: that 
which forms simply the early stage of arterial sclerosis, and another 
process that is apparently independent of this and occurs as a diffuse 
degeneration of the intima and media. The latter form is frequently 
found in the brains of idiots even during early life. Occasionally it 
is also found in senile brains, but in these cases is not so certainly in- 
dependent of arterial sclerosis. Amyloid change of the blood-vessels 
may occur as a part of general amyloid disease, but is not especially 
common in the brain. A rare form of degeneration has been spoken 
of as colloid, although the material discovered in the blood-vessels seems 
more akin to that of hyaline degeneration. In this process the advent i- 
tia and the media are greatly thickened as a result of their infiltration 
with a homogeneous translucent material, which may be deposited 
irregularly in masses or else cause a diffuse thickening of the wall. The 
masses project into the surrounding nervous tissue, and may sometimes 
be detached, forming then independent clumps that are not unlike the 
so-called amylaceous bodies, although they fail to give all the character- 
istic amyloid reactions. This condition is usually associated with 
profound disturbances of the intellect, and may be associated with clinical 
symptoms that resemble those of general paresis. 

Aneurysms may occur in any of the components of the circle of 
Willis. The basilar artery is the one most frequently involved, usually 
just at its posterior extremity. Large aneurysms of the arteries of the 
brain proper, or of the arteries of the vertex are exceedingly rare. A 
saccular aneurysm, as large as a cherry, springing from the anterior 
communicating artery, was observed at the Philadelphia Hospital. 
Miliary aneurysms of the brain are, on account of their relation to 
cerebral hemorrhage, the most important form of vascular disease in 
the brain (see Fig. 234). These aneurysms may be ectatic or saccular. 
The ectatic forms are usually fusiform in shape, and often consist of 
but a single coat of the vessel wall; that is to say, they are merely endo- 
thelium surrounded by a thin layer of fibrous tissue. The saccular 
aneurysms are usually somewhat larger; they appear as bulbous swell- 
ings on one side of the vessel, connecting with the lumen by narrow 
openings. They may consist of a single wall, as in the fusiform type, 
the most common variety, or of the intima or adventitia, with a con- 
siderable amount of fibrous thickening. Occasionally the fusiform 
aneurysms may exhibit distinct atheromatous change, but even in these 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



951 



instances the media is atrophic, and they are certainly exceptional. 
It is doubtful whether arteriosclerosis is of much importance in con- 
nection with the formation of these aneurysms, and it is certain that in 
the majority of cases the first change in the vessel is a fatty degeneration 
of the media. This leads to local weakening of the wall and to conse- 
quent distention — a change that is favored by the considerable dgeree 
of pressure to which the arteries springing from the middle cerebral 




Fig. 466. — Aneurysm of the right vertebral artery (from the Vienna General Hospital 

Collection) . 

or from the beginning of the basilar artery are subjected. According 
to some authors, these aneurysms are to be regarded as herniae of the 
intima, really the result of atrophy of the muscularis; nevertheless, 
they are more frequent in the old, and certainly in the majority of cases 
in which they are found the arteries of the base are distinctly athero- 
matous. The formation of thrombi in miliary aneurysms is exceptional. 

CIRCULATORY DISTURBANCES 

Circulatory disturbances in the brain differ from those in other parts 
of the body on account of the presence of a rigid bony capsule (the 
skull), which prevents any increase or decrease in the size of the con- 
tained viscus. Variations in the quantity of blood, however, do take 
place in adults, and are rendered possible, first, by the elasticity of the 
nervous substance itself, which is capable of undergoing a slight degree 
of compression or extension, and, second, by the free communication 
of the subarachnoid spaces of the brain and cord and the ventricular 
cavities, so that the cerebrospinal fluid may be in greater or less quantity 
in the cavity of the skull or in the spinal canal, and thus permit varia- 
tion in the amount of blood in either region. Local congestion or anemia 
may occur as a result of local disturbances, but the free anastomosis 
of the arteries of the circle of Willis provides such facility in equalizing 



952 



A TEXT-BOOK OF PATHOLOGY 



the amount of blood flowing to the different parts of the .brain that 
neither is often found in general conditions. In very young children 
these mechanical restrictions do not obtain, because the fibrous union 
between the bones of the skull permits of very considerable changes in 
the size of the cranial cavity. 

Acute anemia of the brain may occur as a result of severe hemor- 
rhage, or of hyperemia in other parts of the body, particularly the 
pulmonary and abdominal organs, and it has been supposed to exist 
in fainting, during hysterical crises, and in sleep. It must be admit- 
ted, however, that certain proof of its existence either as a cause or 
effect of these conditions is lacking. Microscopically, the brain is 
usually pale and firm. There is little or no tendency on the part of the 
small venules of the white substance to bleed upon cross-section, and the 
gray matter is distinctly paler, so that the distinction between it and the 
medullary substance is not so distinct as is the case in normal tissue. 
Sometimes in these conditions there is overfilling of the veins of the 
pia as a result of the shrinking of the brain. The changes in the func- 
tions of the brain tissue ascribed to this condition are partly irritative, 
partly paralytic. They are very indefinite. 

Chronic anemia of the brain may occur in severe cachectic condi- 
tions, such as progressive pernicious anemia, lead- or malarial poison- 
ing. It may also be the result, though less frequently, of atheroma of 
the cerebral arteries with a general narrowing of their lumina, or of 
mitral and aortic valvular disease. The brain is small, the consistency 
varies according to the duration and nature of the process, being at 
first hard, later, probably as a result of degenerative changes, slightly 
softer than normal. The ventricles are not dilated at first, but the 
convolutions are shrunken and the sulci are wider as a result of the 
diminution in size of the brain as a whole. The substance of the brain 
/ is pale, and often seems slightly moister than normal. Local anemia 
may occur as a result of thrombosis or embolism, and usually leads 
to softening. 

Active hyperemia of the brain is nearly always associated with 
inflammatory or toxic conditions. It is perhaps most frequent in 
association with meningitis or encephalitis. It is always found after 
death from sunstroke, acute delirium, cholera, and hydrophobia, as 
well as, occasionally, after death from infectious disease. It may be 
local or general. 

Local hyperemia is usually associated with meningitis, and may be 
limited to the superficial layer of the cortex beneath the meningitic 
areas. The affected parts are darker than normal and may even contain 
punctiform hemorrhages. Microscopically the blood-vessels are found 
to be dilated, and there is more or less degeneration of the adjacent 
nerve substance, according to the duration of the process. Local hy- 
peremia may also occur after thrombosis, and leads to red softening 
of the nerve tissue. 

General Active Hyperemia. — The brain is darker and larger and its 
consistency is softer. The blood-vessels of the pia are injected. The 
gray matter is darker and, as in the local form, may contain minute 
hemorrhagic foci. The white matter is moist; its color is rarely altered, 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



953 



but as soon as the section is made it is covered with small red spots, 
representing hemorrhages from the veins and capillaries. These may 
be readily distinguished from interstitial hemorrhages by allowing a 
little water to flow over the surface of the section, when they will disap- 
pear. Microscopically, aside from the distention of the vessels with 
blood, pronounced degenerative changes are rarely found, excepting 
in those cases resulting from infectious diseases. In these the altera- 
tions commonly associated with severe toxemia are present, but are 
to be considered as complications and not as the result of the circula- 
tory disturbances. 

Occasionally, in acute infectious diseases such as typhoid fever, a 
condition occurs in which there is evidently excessive irritation of the 
central substance, manifested by symptoms not unlike those of menin- 
gitis. Postmortem in these cases the only changes found are hyper- 
emia of the brain. Even microscopically no distinct inflammatory le- 
sions can be discovered. This condition has been termed meningismus. 

Passive hyperemia may be associated with valvular heart disease 
or chronic lung disease, or it may be caused by tumors in the neck 
pressing upon the jugular veins, or by intracranial conditions. Of the 
latter, the most important are brain tumors compressing the veins, 
whilst the arteries still continue to convey blood and thus cause increase 
of the cranial contents. When the tumors press upon the veins of Galen 
passive hyperemia and distention of the ventricles are particularly 
common. Passive hyperemia may also be caused by thrombosis of 
the dural sinuses. In acute passive congestion the veins of the dura 
are widely distended; the subarachnoid space is moist; the brain seems 
to be slightly larger, softer and moister than normal. The gray matter 
is of a slaty color. The white matter may have a faint bluish tinge, and 
its capillaries and ventricles bleed freely upon cross-section. The ven- 
tricles may not be larger, but appear to contain fluid under pressure 
that wells forth when they are opened. 

Edema of the brain nearly always occurs when passive hyperemia 
persists, and also occurs in cases of chronic alcoholism. It is character- 
ized by the distention of the subarachnoid space with liquid, so that 
the convolutions are no longer distinct and the surface of the brain has 
a clear or pearly appearance. The arachnoid is usually thicker, par- 
ticularly along the sulci. The fluid is clear, or perhaps very slightly 
turbid; it has a higher specific gravity than the cerebrospinal liquid, 
coagulates upon boiling, and is usually found to contain numerous 
cellular elements. A microscopical examination of the brain and its 
membranes shows marked distention of the subarachnoid space, which 
is usually divided into irregular spaces by delicate fibrous bands. The 
endothelial cells appear to have undergone some proliferation, and in 
many places have desquamated and. lie free in the areolar spaces. 
Around the blood-vessels there is occasionally slight extravasation of 
round cells, which are usually mononuclear and resemble lymphocytes, 
and indicate an inflammatory reaction to the long-continued pressure. 
The arachnoid is usually thicker, the thickening being almost exclusively 
fibrous in nature. The pia is slightly thicker, and sometimes may be 
seen to have coalesced with the superficial layer of the cortex. In the 



954 



A TEXT-BOOK OF PATHOLOGY 



brain substance the perivascular spaces are distended, the neurogliar 
meshwork is coarser than normal, and there may be slight evidences 
of degeneration in the cells. 

Local edema of the brain, the so-called apoplexia serosa, is occa- 
sionally found in the neighborhood of areas of softening. In cases of 
acute hydrocephalus this serous infiltration sometimes occurs in the 
neighboring internal capsules, and may even lead to transient hemi- 
plegia. 

Cerebral hemorrhage occurs in two varieties: the so-called punc- 
tate form and massive hemorrhage. 

Punctate hemorrhages are due to some alteration of the vessel walls 
or of the degree of blood-pressure, causing extravasation of blood into 
the surrounding tissues. The commonest causes are mania, convul- 
sions and encephalitis, traumatism even without physical damage to 
the head as in shell shock and severe infections. The hemorrhages are 
small, often microscopical, and are by far most common in the gray 
matter, especially in the cortex. Grossly such a brain will show red 
or reddish brown spots or streaks which will not wash away; it is best 
to look for them along the sides of the sinuses or on the mesial surface 
of the hemispheres although the basal ganglia are usually likewise affected. 
In shell shock severe hemorrhages are usually found on the surface of 
the brain. The wall of the blood-vessel may be diseased, but does 
not always show solution of continuity, or the hemorrhage may burrow 
along beside the vessel like a dissecting aneurysm, but yet free against 
the nerve tissue. The blood-pigment is more or less altered, according 
to the length of time that has elapsed between the occurrence of the 
hemorrhages and the examination of the tissues. The nervous tissue 
immediately involved is edematous, and there is usually some prolifera- 
tion of the neuroglia cells in the vicinity. Such hemorrhages, of course, 
may heal without leaving any trace, for the secondary degenerations 
that may possibly be caused are too slight to be detected. 

Massive hemorrhages usually occur from the branches of the middle 
cerebral artery- — that is, from the vessels most frequently the seat of 
miliary aneurysms. The arteries commonly involved are the len- 
ticulostriate and lenticulothalamic branches of the middle cerebral 
vessel, and the hemorrhage occurs in the internal capsule. These 
vessels have no anastomoses. Hemorrhages may occur in the centrum 
ovale or the pons, or, in fact, in almost any portion of the central ner- 
vous system. The attack is precipitated by a sudden strain, of physical 
or mental nature, upon a diseased vessel or upon an aneurysm. The 
blood usually collects in the form of an irregular dark-red mass that in 
recent cases rapidly becomes bright red upon exposure to the air. 
The size of the hemorrhagic area naturally varies with its location and 
the amount of blood extra vasated. Its outline is exceedingly irregular 
and almost always separate small hemorrhagic foci are found in the 
surrounding tissue. According to the density of the tissue, the blood 
is more or less dispersed. Thus, in the white matter the extravasation 
is usually more diffuse than in the gray, where hematomata are exceed- 
ingly apt to form. The substance of the brain is soon softened. Its 
structure is usually entirely lost, although it may be possible in recent 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



955 



cases to recognize the presence of altered cells and nerve-fibers. The 
neuroglia usually shares in this softening, but if the hemorrhage is not 
extensive, it may remain and form a sort of skeleton for the blood-clot; 
the tissue then is not nearly so soft, and the surface upon section usu- 
ally is smooth. If the hemorrhage occurs in the internal capsule, as is 
usually the case, and is at all extensive, the blood may creep inward 
toward the ventricle, into which it may rupture, filling the lateral 
ventricle and sometimes extending into the third ventricle and into the 
lateral ventricle on the other side (Fig. 467). Occasionally in exceed- 
ingly severe cases, almost the whole of one of the hemispheres may be 
destroyed; this is usually associated with sudden death, and is known as 




Fig. 467. — Hemorrhage into the internal capsule and the caudate and Jenticular nucleus 
of the right cerebral hemisphere (from Bollinger) . 

the foudroyant form of apoplexy. The softened brain substance can 
usually be readily washed away by a current of water, leaving the blood- 
vessels, which should then be examined with a low power for the pres- 
ence of miliary aneurysms. If the patient survives his first attack, 
rapid alterations begin to take place in the diseased tissue. The throm- 
bus contracts, causing edema in the surrounding tissues. A capsule 
of delicate fibrous tissue may even be formed about it. The small 
hemorrhages in the surrounding tissue are absorbed. The color of 
the softened region becomes dark brown, and it may either go on to 
complete liquefaction, with the subsequent absorption of the pigment 
and the formation of a cyst, or else be gradually entirely absorbed, 
leaving a pigmented scar. The walls of the cysts are usually discolored 
by pigment, and in the neighborhood pigment-granules and compound 
granular cells are found in great numbers. These old hemorrhagic cysts 
are very difficult to distinguish from those produced by other forms of 
softening. Often the contents are slightly discolored, the walls are 
dense and somewhat sclerotic in nature, and may contain crystals of 
hematoidin. It is somewhat doubtful whether the walls are com- 



956 



A TEXT-BOOK OF PATHOLOGY 



posed of neuroglial tissue or of true fibrous connective tissue derived 
from the blood-vessels. It is certain, however, that shortly after ex- 
travasation of the blood, hyperplasia of the neuroglia in the immediate 
vicinity" takes place. This may occur very rapidly, so that in the course 
of a few days new neuroglia fibers may be seen pushing their way into 
the hemorrhagic area from the collection of neuroglia cells in the nearest 
healthy tissue. After healing has taken place the hemisphere is usually 
reduced in size. This reduction is not merely equivalent to the amount 
of nerve tissue that has been destroyed, but represents also the secondary 
degeneration that occurs in the nerve-fibers whose course has been 
interrupted by the lesion. This is both ascending and descending, and 
frequently causes sclerosis that involves not only the brain, but extends 
throughout the pyramidal columns. 

Pathological Physiology.- — The disturbances in the functions of the 
central nervous system produced by hemorrhage are among the most 
interesting in the domain of nervous physiology. At the time of the 
rupture of the vessel the patient almost invariably becomes suddenly 
unconscious and falls, the face is flushed, and there may be convulsive 
movements. This is termed apoplexy. The period of unconscious- 
ness may persist for a longer or shorter interval, according to the amount 
of hemorrhage that has taken place. If the patient recover, the sub- 
sequent changes depend upon the situation of the hemorrhage and 
the extent of the destruction of nervous tissue that has taken place. 
As wiU readily be seen from the description of the pyramidal tract, 
lesion in any part of its course above the first cervical segment produces 
paralysis of the opposite side of the body: if above the middle of the 
pons, paralysis of the lower portion of the face on the opposite side is 
also produced; if below this point, paralysis of the same side. Mono- 
plegias are likely to occur if only a small portion of the fan-like projec- 
tion fibers of the pyramidal tract is involved, such as would be produced 
by a lesion in the cortex or in the centrum ovale. In all these cases only 
the superior motor neuron is affected, and in consequence, either because 
some inhibitory influence is removed or because the lower motor neurons 
are irritated by the products of degeneration, a condition of spasticity 
arises in the muscles. Subsequently, their nutrition is imparled and 
the}" contract. An interesting series of disturbances is produced by 
lesions occurring in those portions of the cortex that have to do with 
manifestations of speech, either receptive or motor. If the former are 
involved, we speak of it as amnesia; if the latter, as aphasia. Lesions 
of the optic tract posterior to the chiasm cause hemianopsia. 

Secondary degeneration after Hemorrhages. — As a result of hemor- 
rhage into the brain substance with destruction of tissue secondary de- 
generations appear, which, of course, are systemic and follow the direc- 
tion in which the nerve-fibers convej" impulses. Of these the most 
important are the degenerations of the pyramidal tract, of the optic 
tract, and of the projection fibers from the temporosphenoid lobes. 
A discussion of this subject involves consideration of the anatomy of 
the brain more than of the pathology, and only the most important 
details can be given here. Degeneration of the 'pyramidal tract may be 
sharply circumscribed if the focal lesion is situated in the cortex or the 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



957 



centrum ovale. In this case a slender band of degenerated fibers may 
be traced along the pyramidal tract. This is only possible, however, 
if the lesion is sufficiently recent to permit the employment of Marchi's 
staining method, for otherwise it is impossible to recognize a small 
number of degenerated fibers in the midst of a group of healthy ones. 
As the hemorrhage usually takes place from the lenticulo-caudate 
artery and involves the complete destruction of the pyramidal fibers 
in the internal capsule, it not infrequently happens that the entire 
pyramidal . column of one side undergoes secondary degeneration. 
Interruption of the fibers of the optic radiation, or destruction of the 
primary optic centers, causes secondary degeneration which does not, 
however, appear as promptly as in the motor fibers. There is degener- 
ation in the external geniculate body, in the pulvinar, and in the anterior 
corpus quadrigeminus of the same side. Ultimately, degeneration may 
also occur in the optic nerves. Destruction of the second and third 
temporal lobes, or of the projection fibers arising from them, causes 
secondary degeneration in the posterior limb of the internal capsule. 
The fibers appear to extend into the thalamus, and also into the crust a. 
Destruction of other parts of the brain cortex causes degeneration, 
which seems to affect chiefly the projection fibers. Extensive hemor- 
rhages into the cerebellum usually cause death, as a result of pressure 
upon the medulla. If, however, the patient survive, and if the nucleus 
dentatus be particularly involved, there is degeneration of the superior 
cerebellar peduncle, which may be traced as far as the red nucleus in 
the tegmentum. All these secondary degenerations are quite typical 
in character. They appear about the ninth day, the first changes being 
the degeneration of the myelin-sheath. This is followed by the appear- 
ance of compound granular cells and hyperplasia of the neuroglia, and 
later corpora amylacea may sometimes be found. Ultimately nothing 
but the neuroglia remains, and this is composed of coarser fibers than 
are found in normal nervous tissue. Occasionally, nerve-fibers without 
myelin-sheaths are found traversing the sclerotic tissue. 

Thrombosis and embolism of the vessels of the brain are due 
to causes that produce the same processes in other parts of the body. 
Embolism will produce attacks of apoplexy like massive hemorrage; 
but thrombosis, while causing paralysis and nerve-tract degeneration, 
does so much more slowly. Thrombosis may occur anywhere. It is 
perhaps more frequent in the basilar artery than in other situations, 
but this rule is by no means certainly established. The causes are, 
of course, chiefly atheroma of the vessels or syphilitic endarteritis. 
Embolism, on the other hand, usually occurs in the artery of the Syl- 
vian fissure. Perhaps 80 per cent, of all cases occur in this situation. 
This frequency is due to the fact that the course of the blood is direct 
from the heart to this vessel, and its importance lies in the fact that it 
is an end artery and, therefore, its occlusion is most apt to lead to cerebral 
necrosis. Less frequently an embolus will lodge in the anterior cerebral, 
but it is probably extremely rare for an embolus to travel along the 
posterior communicating artery and lodge in the posterior cerebral. 
A more frequent route of embolism into the latter artery is along the 
vertebrals to the basilar. Embolism in the basilar artery can, of 



958 



A TEXT-BOOK OF PATHOLOGY 



course, never occur, as its lumen is greater than that of either of the 
branches from which it receives blood. A saddle embolus may occa- 
sionally lodge at its bifurcation and give rise to local thrombosis. 
Sometimes the two processes occur simultaneously — that is, fragments 
of a parietal thrombus in one of the vessels may be washed off into the 
blood-stream and be carried along the artery until they occlude its 
lumen or that of one of its branches. The results of embolism or throm- 
bosis may be either infarction, or, if the obstruction takes place slowl}^ 
as in thrombosis, it then being possible for a collateral circulation to be 
established, there may be no changes or only temporary results. The 
functional disturbances are very similar to those of hemorrhage. As, 
however, the lesions frequently occur very slowly, the sudden shock 
may not occur and the paralysis may supervene without any period of 
unconsciousness. 

Infarction of the brain usually leads very rapidly to cerebral soften- 
ing (encephalomalacia) . It has been usual to describe three forms — red, 
yellow, and white which, while frequently pure in form, are at times 
but stages of the same process, and they do not constitute separate 
pathological entities. 

Red softening corresponds very closely to the hemorrhagic infarct. 
It consists of a serous infiltration of the tissue, the extravasated liquid 
containing numerous red corpuscles. The same theories that have 
been suggested for the explanation of a hemorrhagic infarct have been 
used to explain its occurrence. 

Yellow softening is really only the red softening after more complete 
liquefaction has taken place and most of the pigment has been absorbed. 

White softening is a term applied to two very different conditions. 
The first corresponds to the anemic infarct, and appears very shortly 
after the occlusions of the vessels. The second is a late stage of any 
form of softening, and is characterized by the occurrence of an excessive 
amount of fat in the softened area, producing an emulsion. The white 
color becomes even more pronounced after the fat has been absorbed, 
and the lesion is represented only by coarse neuroglia fibers. 

Macroscopically, the earliest changes usually appear toward the end of 
the first twenty-four hours. The brain substance in the softened area is 
swollen, softer, and somewhat mottled in appearance and may even 
exhibit small punctiform hemorrhages. The lesion is not sharply 
delimited, but fades gradually into the surrounding tissues. If a large 
artery has been obstructed, a considerable portion of the brain may be 
softened and there will be a large extravasation of blood. In this 
case the parts of the brain showing the greatest alteration are those 
nearest the periphery of the distribution of the obstructed vessel, and 
these changes may even occur without complete obstruction if the 
general circulation is impaired, as in valvular heart disease, or as a 
result of profound general anemia. As the process continues, more and 
more blood is extravasated into the tissue, giving it a bright-red appear- 
ance. The lesion by this time becomes more circumscribed, although the 
surrounding tissue may be somewhat softened, and as in the case of cer- 
ebral hemorrhage, may contain punctiform hemorrhages. As soon as the 
demarcation is complete the brain tissue becomes rapidly softer, prob- 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



959 



ably as a result of the obstruction of the lymph-channels by which the 
nutritive fluids enter. The nerve cells undergo almost complete degen- 
eration; they lose their axis-cylinders and their tinctability, and may 
either disappear completely or be no longer recognizable. The myelin- 
sheaths undergo a fatty degeneration, in which the nerve-fibers soon 
take part. The whole tissue is filled with compound granular cells. 
The neuroglia fibers may also become softened and, to a large extent, 
liquefied, although they persist longer than the other elements. The 
wall of what has now become a cyst is composed of the surrounding 
neurogliar tissue, newly formed capillaries, and nervous tissue in an 
advanced stage of degeneration. The blood-vessels, however, usually 
persist for- some time, although they are filled with thrombi and form 
an irregular spongy network in the lesion. 

When organization commences the blood-pigment gradually disap- 
pears, and the material changes from a brownish, turbid fluid to a lighter 
yellow mass, often irregularly surrounded by deeply pigmented cells. 
Later, complete contraction takes place, and scar, composed chiefly 
of neuroglia tissue, but also containing some fibrous connective tissue 
that has developed from the walls of the blood-vessels, is left. It is, 
of course, clear that red softening is more frequent in the vascular parts 
of the brain, and white softening in those regions that are poorly sup- 
plied with blood, particularly in the white substance of the cerebrum. 
The areas are rarely as well circumscribed as those of red softening, and 
often do not lead to complete destruction of the tissue, causing only 
numerous adjacent minute focal lesions, the so-called etat crible. 

A peculiar form of softening occurs in the cortex of the brain. It is 
usually found in lesions that have existed for some time. The area is 
yellow, depressed, and somewhat circumscribed. The pia mater over 
and around the lesion is somewhat thickened, and often the surround- 
ing blood-vessels show thickening of the walls, although this latter 
change is probably the cause and not the result of the gross lesion. 
These are the so-called plaques jaunes of French writers, and if extensive 
they lead to considerable retraction of the brain substance and to the 
formation of collections of liquid in the subarachnoid space {hydrops e 
vacuo; external hydrocephalus). 

Areas of softening, probably due to capillary thrombosis, are fre- 
quently found in children suffering from tuberculous meningitis. They 
may also occur in other forms of meningitis, and also in encephalitis, 
although in these latter conditions the presence of pyogenic micro- 
organisms in the emboli lead to somewhat different changes, which 
will be described in connection with encephalitis. Traumatism may also 
cause softening, often multiple in character, and not necessarily situated 
directly beneath the point of injury. As a result of the destruction of 
tissue, secondary degenerations occur that differ in no respect from 
those following hemorrhage. 

INFLAMMATION 

Encephalitis, or inflammation of the brain substance, is prob- 
ably not essentially different from inflammation of the other tissues in 
the body. The nature of nervous tissue, however, and the peculiar 



960 



A TEXT-BOOK OF PATHOLOGY 



reaction that it manifests to various injurious agencies, render this 
subject one of the most doubtful and difficult in the pathology of the 
central nervous system. The various forms may be classified, first, as 
acute and chronic. The important forms of acute encephalitis are the 
parenchymatous, the simple, the hemorrhagic, and the suppurative. 
Chronic encephalitis may take the form either of sclerosis or of scar- 
formation, the latter really only a modification of the former. Acute 
encephalitis may be considered to be disseminated or focal. 

Acute parenchymatous encephalitis is rather a form of degeneration 
than of specific inflammation. Changes in the nerve-cells without 
associated vascular phenomena have been observed and described in 
a number of intoxications, either the result of direct poisoning or in- 
fection. More or less extensive changes have been recorded as a 
result of poisoning by alcohol, arsenic, and other poisonous substances. 
Of the infectious diseases that have been studied, the most important 
are diphtheria, tetanus, leprosy, and hydrophobia. The most important 
and typical changes have been already described in the section upon 
degeneration of the nerve-cells. These forms of encephalitis, if the name 
may properly be applied to them, may lead to death, but recovery even 
from the advanced stages is not impossible. Neither the brain nor the 
cord in these cases exhibits any macroscopical changes, excepting, per- 
haps, passive congestion of the membranes when death was preceded by 
violent convulsions, as in tetanus. 

Simple acute focal encephalitis is characterized by the development, 
in various parts of the brain, of areas of softening that may range from 
a millimeter to several centimeters in diameter. They are usually 
irregular in size and very indistinctly separated from the surrounding 
tissue. The most common situations are the region of the third and 
fourth ventricles and the aqueduct of Sylvius. The gray matter is 
more often involved than the white. Polioencephalitis is a localized 
cerebritis of the basal ganglia bulb or pons, or all of these, affecting 
chiefly the motor ganglia, with cytolysis, and some cellular infiltration 
around them and about the blood-vessels. It is more extensively con- 
sidered under Poliomyelitis. 

Etiology. — The cause is probably in all cases the presence of infec- 
tion in the body, such as influenza, typhoid fever, or septicemia. Au- 
thors, whose opinions we must respect, have, however, described en- 
cephalitis as the result of simple concussion of the brain, or of various 
forms of poisoning, such as lead. The difficulty in the latter group of 
cases is due to the close resemblance between encephalomalacia and 
encephalitis. Collections of round cells, with slight degenerative changes 
in the nervous system, have been described in chorea, and have been 
supposed to represent the subacute or chronic form of encephalitis. 
The observations are, however, at present insufficient to establish this 
point. References will be made again to it under the heading of Chronic 
Encephalitis. 

Pathological Anatomy. — The two most important changes are those 
in the color and consistency. The former is usually slightly darker than 
normal, but may, if, as is not infrequently the case, extensive hemorrhage 
has occurred, become a bright red, resembling, upon inspection, an area of 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



961 



hemorrhage, or perhaps more closely, an area of red softening. The 
consistency is always decreased, probably as a result of serous infiltration. 
Often the diseased area projects slightly from the surface of the section. 
Microscopically, the characteristic change is the perivascular round-cell 
infiltration. This usually involves the majority of vessels in the lesion, 
and m&y also be found in regions of the brain in which softening has not 
already commenced. Usually there is the characteristic inflammatory 
congestion, the blood-vessels, particularly the small capillaries, being 
sometimes greatly distended and packed with red blood-cells. In some 
cases thrombi have formed. Hemorrhages are exceedingly frequent; 
these are sometimes punctiform and sometimes diffuse extravasations into 
the tissue. Often they appear to represent ruptured capillaries, and 
produce a peculiar speckled appearance on the surface of section. In the 
early stages the cellular exudate is chiefly composed of polynuclear 
leukocytes. Later they are replaced by mononuclear cells, probably 
representing proliferation of the endothelial cells, and perhaps of the 
neuroglia cells. The nerve cells and fibers in the affected region undergo 
the ordinary degenerative changes. In the midst of the focus the neuro- 
glia ordinarily shares in the softening. At the periphery there is usually 
a noticeable proliferation of the neuroglia cells and the formation of a 
coarse, thick network of neuroglia fibers. Of course, these changes are 
not found about very early lesions. In the earliest staggs compound 
granule cells are usually absent; later they may appear in considerable 
numbers, but their presence is by no means sufficient to indicate the 
existence of an acute or chronic inflammatory process. Ordinarily, in 
these forms of encephalitis, the rest of the brain exhibits no macroscopical 
changgs, and often none can be detected by the microscope. t The 
membranes are smooth, the vessels of normal elasticity, and not sur- 
rounded by a round-cell infiltration. Complete resolution may perhaps 
occur; of course, this can only be supposed from the clinical symptoms 
of the disease, there being no definite experimental or pathological evi- 
dence to support it. 

The focal lesions may undergo softening and lead ultimately to scar- 
formation, and if they are extensive there will be considerable atrophy 
of the affected part of the brain. The great majority of cases, however, 
in all probability terminate fatally. The nature of the process is gener- 
ally accepted to be primarily vascular, the secondary changes being the 
result of alteration in the nutrition of the surrounding part. 

Suppurative encephalitis has already been in part described in con- 
nection with purulent meningitis. In that condition, the pyogenic 
emboli appear to enter the brain substance along "the lymphatics that 
dip into it from the pia. They are usually small, not circumscribed, 
and more apt to be found in the gray matter of the cortex, particularly 
near the base of the brain and in the structures adjacent to the ventricles, 
than in the white substance. Occasionally larger collections, forming 
rather ill-defined abscesses, are found. In a brain that one of us removed 
at autopsy the changes in the pia arachnoid were slight and were limited 
to a small area over the motor region for the leg on the left side, but 
beneath this there was an extensive area of purulent infiltration of the 
brain substance, not sharply circumscribed. 

61 



962 



A TEXT-BOOK OF PATHOLOGY 



Abscess of the brain is a condition characterized by the presence 
in the brain substance of one or more cavities containing pus. The 
usual cause is suppurative bone disease, particularly that resulting 
from otitis media. This condition may, however, occur in general 
pyemia as a result of metastasis from some neighboring or remote focus 
of suppuration. Suppuration may also occur in the course of pneu- 
monia, or in chronic suppurative diseases of the lungs, such as fetid 
bronchitis. Direct infection of the brain, either experimentally or as 
a result of wounds penetrating the skull, has also been observed. In 
many of these cases the nature of the transmission is clear; thus the 
abscess resulting from otitis media, disease of the ethmoidal sinuses, or 
from direct inoculation, is usually situated in the immediate neighbor- 
hood of the original focus. Abscess secondary to pulmonary disease 
is usually found at the base of the cerebral hemispheres, and is probably 
transmitted along the retropharyngeal lymphatics. Abscess due to 
injury without penetration of the skull has occasionally been recorded; 
sometimes it is found in the contused area, sometimes on the opposite 
side of the brain. The micro-organisms that have been found in the 
pus include practically all the pyogenic forms. The most frequent are, 
perhaps, the staphylococcus, the streptococcus, and the pneumococcus. 
Occasionally the actinomyces, the Bacillus pyocyaneus, and the Myc- 
bacterium tuberculosis have been found, the latter in cases that were 
apparently acute abscesses of the brain, and not softened solitary tuber- 
cles. 

Statistical studies of the literature show that in about two-thirds 
of all cases the cerebrum is the seat of the lesion; in the remaining third 
it is chiefly the cerebellum. This distribution does not, of course, 
apply to the disseminated forms of purulent encephalitis. Solitary 
abscesses are usually the result of embolism or extension from the bones. 
They may be small or of considerable size, and one is on record from 
which 400 c.c. of pus were removed. They may be either surrounded 
by softened brain substance or distinctly encapsulated. The latter 
condition usually occurs if they have lasted any length of time — that is, 
three or four weeks; although cases are on record in which a distinct wall 
did not develop about an abscess that had existed for several months. 
The contents of the cavity are pus and detritus, and in it may frequently 
be found thrombosed blood-vessels. The surrounding brain tissue is 
usually undergoing softening. It may be either white, or, as a result of 
hemorrhagic extravasation, red in color. The abscesses usually spread 
more or less gradually; that is to say, there is probably no tendency to heal 
spontaneously. If large, they cause considerable intracranial pressure, 
which is indicated by the flattening of the convolutions or bulging of the 
brain after the skull has been trephined. Those due to punctured wounds 
are usually associated with meningitis. Those due to caries must also be 
associated with inflammatory changes in the meninges, and not unfre- 
quently there is thrombosis of the cerebral sinuses. Microscopically, we 
find the ordinary characteristics of pus. The wall or periphery is usually 
undergoing fatty degeneration, and there is a considerable accumulation 
of round cells in the surrounding tissue. Metastatic abscesses are usually 
multiple. A group may be found either in one situation in the brain or 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



963 



they may be very widely distributed. In cases of severe encephalitis 
more or less pronounced changes may be observed in the ganglion-cells in 
other parts of the central nervous system. 

Primary Acute Hemorrhagic Encephalitis. — Strumpell described 
under this name a form in which the dura was normal but somewhat 
dry; the pia injected, the centrum ovale softened, edematous, slightly 
pinkish or gray, and marked by fine hemorrhagic points. Microscopic- 
ally there were no granular cells, but drops of myelin and some detritus. 
There was some hyperemia and cellular infiltration of the pia. The 
ganglion-cells of the cortex were normal. In the white matter the 
vessels were distended with blood and surrounded by thick masses of 
round cells; the perivascular spaces were distended; the neuroglial- 
tissue coarser than normal. In many situations there was bleeding 
from the capillaries. A modification of this condition is seen in epidemic 
or lethargic encephalitis which we have already discussed on page 371. 
The lesions, while irregularly generalized, are more outspoken in the 
basal ganglia and in many ways resemble those of polioencephalomyelitis 
although somewhat more definitely hemorrhagic. 

Chronic encephalitis may take the form of sclerosis or of scar- 
formation, which is really but a variety of sclerosis. (See Neuroglia.) 

Lobar sclerosis is usually an extensive but sharply circumscribed 
process affecting the whole or part of one or more lobes of the brain. 
The involved area is usually considerably diminished in size. The con- 
volutions are smaller, the sulci broader, but, of course, not so deep; the 
surface is often finely granular, and the pia is adherent. The consistency 
is greatly increased, the tissue being almost like cartilage. Micro- 
scopically there are the same changes found in the other forms^-that is, 
excessive proliferation of the neuroglia, with partial or complete disap- 
pearance of the nervous elements. The cause appears to be some 
vascular disturbance occurring during fetal existence, as the localiza- 
tion nearly always corresponds to the distribution of one of the arteries 
supplying the brain. If the anterior cerebral artery is affected, the 
frontal lobe is sclerotic. If the artery of the Sylvian fissure is involved, 
there will be sclerosis of all the hemisphere, with the exception of a part 
of the occipital lobe; and if the lesion is situated on the proximal side 
of the lenticulostriate artery, this part will also be degenerated. If 
the posterior cerebral artery is occluded, the lesion will be found at the 
tip and in the lower half of the occipital lobe. Extensive secondary 
degeneration always occurs in this form. 

There are, besides the scleroses based upon developmental defects, 
numerous forms of degenerative or sclerotic processes of the brain, 
ganglia and cord which are divisible for clinical purposes into more or 
less definite entities. Their fundamental pathology is essentially that of 
neural degeneration and glial overgrowth, with or without vascular 
lesions. Perhaps the most important single forms of a generalized process 
of this nature are paralysis agitans, senile dementia and paresis (the last 
perhaps a definitely low grade inflammatory lesion) while insular sclerosis 
is exemplified by multiple sclerosis, where the lesions are widespread, and 
by the more limited forms like lenticular degeneration ; the pathology 
of the insular varieties is essentially the same in all cases. 



964 



A TEXT-BOOK OF PATHOLOGY 



Paralysis agitans is a clinical entity for which there has been reported 
no uniform or definite pathology, although certain lesions are frequently 
encountered. They are usually found in the basal ganglia, especially the 
striate body, peduncles and upper cord, spreading upward and downward 
because the ganglion cells are destroyed. The essential histological 
change seems to be a degeneration of ganglion cells, in all probability by 
lack of nutrition since there is always some grade of endo- or periarteritis, 
with perivascular and periganglionar cellular infiltration. As might be 
expected gliosis and fibrosis appear, compressing nerve elements, both 
cells and fibers. When the lesions are limited to the lenticular nucleus, 
there is apt to be some lateral tract involvement; this, with atrophic 
hepatic cirrhosis, constitutes what is known as Wilson's disease. 

Huntingdon's chorea is a gliosis of the anterior part of the brain with 
neural degeneration and atrophy leading to sclerosis of the anterolateral 
and cerebellar tracts. Because of the associated pachy- and leptomenin- 
gitis, it is suggestively inflammatory in nature. 

Senile atrophy is sometimes exaggerated sufficiently to lead to demen- 
tia, in which case the process is less of an inflammation and more of pure 
nutritional retrogression, based upon vascular, disease. The brain is 
usually smaller than normal and covered with opaque thickened pia, the 
vessels of which may be sclerotic; an internal hemorrhagic pachymen- 
ingitis is often present while it is common to find an external hydro- 
cephalus and sometimes an internal one also. The gyri are small and 
irregular, the sulci gaping. The cord may show similar changes. The 
minute lesions consist of arterio-capillary fibrosis, or atheroma in the 
larger vessels, with marked disappearance of the ganglion cells and 
naturally of the related fibers; the prevailing type of change is fatty 
degeneration. In the areas from which nervous tissue has disappeared, 
round and granule cells and free pigment are discovered. Glial hyper- 
plasia is marked especially near the cortex, perhaps being greatest in 
Amnion's horn. As might be expected, areas of red or white softening 
are sometimes seen. Fatty and gliomatoid plaques are encountered both 
over the surface, within the brain and on the cord. 

Multiple or disseminated sclerosis is a condition characterized by 
the formation throughout the nervous system of various foci of irregular 
size and distribution in which the neuroglia is somewhat hyperplastic, 
the myelin-sheaths more or less degenerated, and the axis-cylinders, as 
a rule, slightly, if at all, affected. When sclerotic areas affect the white 
matter of the brain and cord they appear as grayish or grayish-pink 
areas or plaques which may, if at the surface, be observed through the pia. 
They resemble the gray matter of the cord too closely to be clearly distin- 
guished from it. Their edges are usually sharp. After hardening in 
Muller's fluid they appear of a bright yellow color and are exceedingly 
distinct. The smallest may be only a millimeter in diameter, and the 
largest may occupy the whole transverse section of the spinal cord or 
even entire convolutions of the brain. Occasionally sclerotic areas 
may be found in the nerve-roots. The most important change that is 
found upon microscopical examination is a thickening of the walls of 
the blood-vessels, surrounded by a zone of proliferated glia tissue of 
irregular width and arrangement. The vessels may be thickened by 



DISEASES OF THE BRAIN AND ITS MEMBRANES 965 

hyaline degeneration, and the productive changes with the degeneration 
lead to narrowing of the lumen. The perivascular lymphatic space is 
often filled with cells containing droplets that stain black with osmic 
acid. Occasionally the vessels appear to be increased in number, al- 
though this is possibly due to contraction of the surrounding tissue 
bringing them more closely together. In the center of the foci the 
neuroglia cells are not markedly increased; in the periphery, however, 
they seem to have undergone a distinct hyperplasia. The neuroglia 
fibers throughout are somewhat thicker and more irregular, and form a 
large-meshed network. In the midst of the neuroglia compound granular 
cells and amyloid bodies are often found. If stained by Weigert's 
method, it is at once evident that the myelin-sheaths have disappeared 
almost entirely, all the sclerotic areas appearing bright yellow. If the 
Marchi method be used, however, a certain number of degenerated 
myelin-sheaths will be found, as a rule, still present. The edge of the 
sclerotic area does net end as sharply as appears macroscopically, but 
gradually fades into the healthy tissue. The axis-cylinders, in spite of the 
destruction of the myelin-sheaths, are nearly always present and appar- 
ently normal, a fact which explains the absence of secondary degeneration 
beyond the lesions. In those situations where the hyperplasia of the 
neuroglia fibers is most pronounced, the axis-cylinders may be swollen or 
show partial fatty degeneration, or be entirely absent. The ganglion- 
cells are shrunken and pigmented, and may, in rare cases, completely 
disappear. In advanced cases of the disease the process resembles more 
closely a chronic myelitis; the axis-cylinders passing through the lesion 
may be totally destroyed and secondary degeneration occur. In those 
cases that have been studied in the early stages of the process perivascular 
inflammatory changes have been present, and it is about these that the 
sclerotic areas have formed. In some cases thrombi have been also de- 
tected in the vessels, and many of them show the early stages of hyaline 
degeneration. For this reason, and because disseminated sclerosis fre- 
quently develops after an infectious disease, it is generally accepted that 
the process is due to infectious embolism. Certain authors, however, 
hold that the vessels are not the primary origin of the disease, as in many 
of the sclerotic foci they are perfectly healthy. 

General Progressive Paralysis. — Paresis. — There has been much 
diversity of opinion concerning the true nature of general progressive 
paralysis but the safest conception is perhaps that it is a cortical degenera- 
tion and sclerosis, often with similar lesions in the spinal cord, associated 
with a mental change which proceeds to dementia, and with motor 
paralyses. 

The etiology is not yet clear, but some assistance has lately been 
given in the finding by Noguchi of the Spirochceta pallida in the brain 
of paretics. He has succeeded in showing the presence of these spirals 
in a goodly proportion of cases, in a few instances in enormous numbers, 
not only in the brain, but in the cord, especially of taboparetics. Clin- 
ically, it is difficult in many cases to get a history of syphilis, but the 
Wassermann reaction of the blood or spinal fluid is usually positive. 
However, all cases of syphilis of course do not end in paresis so that 
contributory causes must be sought. This disease is more common 



966 



A TEXT-BOOK OF PATHOLOGY 



among civilized communities than in primitive people, a fact that sug- 
gests the influence of the competitive struggle for livelihood; further 
analysis would indicate that more educated than ignorant people suffer 
this dementia. However since every case of syphilis does not end thus it 
has been suggested that certain strains of the spirocheta pallida have a 
predilection for the cerebral cortex. Hard work especially mental, 
severe strains, alcoholism and perhaps traumatism lay the foundation for 
the spirochete. Males between 30 and 45 are most commonly attacked; 
juvenile cases probably rest on a congenital infection. 

The changes found most frequently are as follows: the dura mater 
is adherent to the skull; it may be thickened, and often shows upon its 
under surface the exudate of a hemorrhagic pachymeningitis. The 
arachnoid is thickened and opaque, particularly along the course of the 
veins; and in the subarachnoid space there is often a considerable effusion 
of liquid. The pia mater is thickened and opaque and may or may not be 
adherent to the cortex; in the latter case the subpial areolar tissue is 
distended with fluid. Microscopically, there is often found a round-cell 
infiltration about the blood-vessels; their walls are thickened and show 
some hyaline degeneration. The fluid in the areolar spaces may be clear, 
or as in more commonly the case, it is viscid and even colloid in nature. 
The gross appearance of the brain is frequently considerably altered. 
The convolutions are flattened; the sulci broader than normal; the con- 
sistency of the brain is slightly increased; the cortex is usually pale and 
greatly reduced in thickness. The white matter may appear to be 
slightly looser in texture, but ordinarily presents no change. Micro- 
scopically, the blood-vessels in the cortex have thickened walls and 
occasionally one is found with a completely obliterated lumen. There is 
usually distention of the perivascular spaces, which may be filled with 
plasma cells and various products of degeneration, such as pigment 
granules. The real connective tissue is usually extensive, taking its 
origin from the vascular adventitia. The glia-cells are greatly increased 
in number, although it is difficult to decide whether this is absolute or 
relative. The neuroglia fibers are usually slightly coarser than normal. 
The tangential fibers of the cortex may be reduced in number or entirely 
absent. The ganglion-cells exhibit a great variety of alterations. The 
protoplasmic processes are varicose, and when sufficiently well impreg- 
nated show the absence of the gemmules. The axis-cylinder is usually 
distinct, due to the degeneration of the myelin sheath. The body of the 
cell may be irregular and vacuolated, and there is often extensive chro- 
matolysis. The ventricles of the brain are usually slightly distended, 
probably the result of simple atrophy, and the choroid plexus is often 
cystic. Changes are frequently found in the spinal cord. The ganglion- 
cells in all parts show pronounced degenerative characteristics. This is 
particularly interesting in view of the fact that the motor symptoms 
progress so gradually. The posterior roots are often slightly degenerated, 
and there is systemic degeneration of the posterior columns not unlike 
that found in the early stages of tabes dorsalis, excepting that ordinarily 
it is most pronounced in the cervical region. The pia and arachnoid of 
the cord, particularly those portions covering the posterior columns, are 
thickened and more or less adherent. The dura is often markedly thick- 
ened and may exhibit pachymeningitis. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



967 



INJURIES TO THE CENTRAL NERVOUS SYSTEM 

Injuries to the central nervous system produce a great variety 
of lesions, according to their nature and severity. 

Concussion, either from a single shock or from repeated blows, may 
give rise to transient or permanent changes. Ordinarily there is con- 
siderable hemorrhage at the site of the blow. This may be either be- 
tween the dura and the skull or between the arachnoid and the pia. 
Small hemorrhages are not infrequently found in the central nervous 
substance, and appear to occur particularly in the direct line of the 
force applied to the skull. In the latter case autopsies have shown the 
existence sometimes of multiple hemorrhages, sometimes of disseminated 
areas of sclerosis in the white and the gray substances. Not infre- 
quently hemorrhage is also found in the subarachnoid space of the 
opposite side (hemorrhage by contrecoup). This is explained either by 
supposing a flattening of the elastic skull or by ascribing it to the force 
with which the brain rebounds against that side. Occasionally in the 
spinal cord, after experimental repeated concussions, changes somewhat 
systemic in character and affecting chiefly the posterior columns have 
been observed. The hemorrhages may be punctate or, in some cases, par- 
ticularly if the injury is severe and the arteries are diseased, massive. 

Lacerated wounds of the brain are usually produced by fracture of 
the skull. There is extensive interstitial hemorrhage and softening, 
and the surrounding tissue is edematous. If only subdural hemorrhage 
occurs, it may produce compression with secondary yellow softening. 
Any of these lesions may heal with the formation of a scar and the pro- 
duction of more or less extensive secondary degeneration. Extensive 
lacerations of the brain are sometimes the result of injury during birth, 
giving rise to so-called cerebral palsies of childhood. In these cases, 
as the central nervous system is not fully developed when the injury 
occurs, there is hypoplasia of the affected parts. 

Punctate wounds of the brain are due to fragments of bone, to sharp 
instruments, or to bullets. In nearly all cases a certain amount of 
infection occurs, giving rise, to encephalitis. The injured area usually 
undergoes complete necrosis, and this extends for some distance into 
the surrounding tissues. The necrotic area is composed of a granular 
detritus, in the midst of which are found altered blood-pigment and 
broken-down nuclei. At the periphery there is usually some granulation 
tissue, proliferation of the neuroglia, and more or less round-cell infil- 
tration, according to the intensity of the inflammatory process. Experi- 
mental lesions may be produced in various ways, the most interesting 
results, perhaps, being those found after the introduction of foreign 
bodies or after careful aseptic laceration. In either case, shortly after 
the operation, necrotic changes will be found in the injured area. There 
is marked proliferation of the neuroglia cells, even as early as the third 
day, and of the neuroglia fibers. New capillaries may be seen pushing 
into the area, the endothelial cells of their walls exhibiting karyokinetic 
figures. The nervous tissue in the immediate neighborhood is in various 
stages of degeneration. If there has been much hemorrhage, the blood- 
pigment will be found in irregular homogeneous masses or in the form of 



968 



A TEXT-BOOK OF PATHOLOGY 



hematoidin crystals. Later, evidences of regeneration in the nervous 
tissue may be observed, particularly the appearance of karyokinetic 
figures in the nuclei of the ganglion-cells. The injured area is ultimately 
replaced by a mass of coarse neuroglia fibers containing, usually, fewer 
cells than normal. That true regeneration of the central nervous 
system ever occurs in the human body is exceedingly doubtful; indeed, 
it is not certain that it occurs in any of the vertebrates, although after 
removal of the tail in lizards a spongy mass of neuroglia may be found 
in the new organ. 

Compression of the brain is due to tumors or to various infiltrative 
and exudative processes more or less localized. The most common are 
those occurring from hemorrhage between the skull and dura, or between 
the latter and the pia. (See Concussion.) The effect is to compress 
the gyri, causing interference with their function, blood-supply, and 
nutrition. The foreign mass may be partly absorbed, but usually 
something remains, like a cyst with thickening of the meninges, press- 
ing into the brain substance, with the formation of concavities of 
various shapes (traumatic porencephaly) . . 

INFECTIOUS DISEASES 

Tuberculosis occurs in the brain in the form of miliary tubercles 
or as large masses, the so-called solitary tubercle, or tyroma. 

The condition is always secondary and comes through the blood- 
stream or by extension (bone), usually the former. 

Miliary tubercles are met with in association with tuberculous 
meningitis. They are most frequent at the base of the brain. 

Solitary tubercles occur independently of tuberculosis of the men- 
inges. They occur most often in the cerebellum in which location they 
may compress the aqueduct of Sylvius so that hydrocephalus not infre- 
quently arises. They are more frequent in children than in adults, and 
usually occur in cases in which there is tuberculosis of other parts of the 
body, notably the lymphatic glands. The infection reaches the brain 
through the blood-vessels. The lesions are rounded masses of grayish or 
yellowish color, sometimes showing fresh gray tubercles at the periphery. 
The growth of the mass is caused by increase in size of the original 
tubercles with inclusion of new-formed tubercles at the periphery. 
Early caseation is usual. Secondary infection of the pia sometimes 
occurs. 

Occasionally there is a sclerosis in the vicinity of the large mass, 
arising from glia proliferation or from fibrous tissue in the adventitia 
of blood-vessels. 

Syphilis appears in the brain in the form of gummata or as a diffuse 
vascular disease with secondary degenerative conditions, such as are seen 
in tabes and paresis. The name parasyphilitic nervous disease was 
formerly given to these conditions, before the spirochete pallida was found 
within their lesions, because unequivocal evidence was not at hand 
that they were connected with syphilis. While they are now recog- 
nized to be surely syphilitic in origin, their pathology is seldom that of 
syphilitic granulation tissue as it is known elsewhere in the body, a fact 
which can be seen by consulting the respective descriptions. The most 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



969 



common variety of syphilis of the nervous system is a meningo-en cepha- 
litis of the base, involving frequently the optic tract and the sheaths 
of cranial nerves. The lesions are described under the meninges. 

Gummata usually begin in the subarachnoid space, originating in the 
membranes and involving the brain substance secondarily. The dura 
may be simultaneously involved, and the three membranes may be 
adherent to each other and firmly attached to the brain. Primary 
gumma of the brain substance is certainly very rare. In the earlier 
stages the gumma is a grayish and rather translucent growth, ^but 
secondary caseation occurs so rapidly that the primary stage is rarely 
observed. As a rule, the lesion appears in the form of an irregular, dry, 
caseous area occupying the cortical portion of the brain and attached 
to the pia and arachnoid, and even the dura. The cerebral substance 
surrounding the growth is more or less softened and degenerated. 
The blood-vessels in the affected area or its vicinity are the seat of 
endarteritis, which in some causes complete occlusion of the lumen. 
In hereditary syphilis symmetric gummata of the brain are occasionally 
found. 

Syphilitic disease of the blood-vessels of the brain takes the form 
of more or less diffuse peri- and endarteritis involving principally the 
basal vessels or the middle cerebral artery. Secondary degenerations 
and softening, or sclerosis, of a diffuse or focal character, may result 
from the vascular disease, but neither these changes nor the vascular 
lesions are peculiar and distinctive. 

Actinomycosis of the brain is generally secondary to actinomycosis 
of the tissues of the neck, and results from extension upward through 
the base of the skull. The membranes are first involved, the brain 
substance secondarily. The lesion may take the form of a chronic 
abscess or may be tumor-like in appearance. 

TUMORS 

The most common is probably glioma, but almost equally as common 
is sarcoma. Cholesteatoma, lipoma, endothelioma, and teratoid cysts 
also occur, but they spring from the membranes and have been de- 
scribed in connection with them. 

Glioma usually appears as an infiltrating mass, causing little altera- 
tion in the structure of the brain, somewhat harder in consistency 
than the brain substance and slightly darker. It is rarely a multiple 
growth, and shows no marked predilection for any particular portion of 
the brain, although it occurs more frequently in the cerebral hemispheres 
than in the basal ganglia or the cerebellum. It always springs from the 
neurogliar tissue of the central nervous system, and is remarkable for 
its extreme richness in cells. Usually, the tumor is exceedingly vascular, 
the vessels consisting of small capillaries or larger spaces lined with 
endothelium, and this vascularization may be so excessive that the 
tumor in parts has a delicate pinkish or reddish color, giving to the 
cross-section a mottled appearance. In some cases the consistency 
of the tumor is quite hard, and in these the cellular elements are de- 
creased in amount proportionately to the fibrous tissue. Ordinarily 
true nervous tissue is absent from the midst of the tumor, the mass in 



970 



A TEXT-BOOK OF PATHOLOGY 



the center being made up of the neuroglia tissue. This gradually 
diminishes toward the periphery, and ultimately fades into the true 
nervous tissue that may be somewhat edematous. In some cases, 
however, as in ordinary sclerosis of the central nervous system, myelin- 
ated nerve-fibers may be found in the midst of the tumor, and it fre- 
quently happens that the secondary degeneration extending from a 
glioma is much slighter than the apparent extent of the process would 
lead one to expect. Occasionally, either glioma cells, or possibly 
ganglion-cells, that have undergone proliferative changes in the midst 
of the growth, may be found. These are much larger than the ordinary 
cells, and contain numerous branched processes and often one or several 
large nuclei. This is the so-called ganglionar neuroglioma. Very rarely 

tumors are encountered that seem 
to be composed almost entirely of 
ganglion cells and nerve fibers, 
ganglioneuroma. All these tumors 
have been extensively discussed 
under neoplasms from nervous 
tissue. 

Sarcoma of the brain is prob- 
ably the next most frequent tumor. 
It usually occurs in middle adult 
life, although it is quite frequent 
in children. The commonest seat 
is the cortex, which it probably 
invades from a primary focus of 
proliferation in the membranes. 
The tumors are ordinarily nodular 
growths, usually distinctly circum- 
scribed from the surrounding tissue, 
and in some cases even surrounded 
by a fibrous capsule, from which 
they can be readily removed. They 
are rather firmer than the brain 
tissue, and sometimes slightly um- 
bilicated if at the surface. The surface of section is pale and dry, but fre- 
quently mottled on account of the presence of hemorrhages. If primary, 
the sarcomata are single; if secondary, more frequently multiple. Histo- 
logically, almost any type of sarcoma may be found, the most frequent 
perhaps being the round-cell, non-pigmented form. Giant cells are 
very frequently found. Ordinarily the tumors are extremely vascular, 
and occasionally contain interstitial hemorrhages. The surrounding 
brain tissue shows the symptoms of marked compression, is edematous, 
and may contain small interstitial hemorrhages. The true nervous 
substance is ordinarily degenerated, and we find extensive secondary 
degeneration as a result of the presence of the tumor. 

Many authors believe that a combination of glioma and sarcoma 
may occur, and gliosarcomata have been frequently described. As 
the neuroglia tissue has the functions of connective tissues, and in many 
respects resembles it in its pathological processes, it is natural that a 




Fig. 468. — Multiple caseous tubercles of 
the brain (from the Vienna General Hospital 
Collection) . 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



971 



glioma should be similar to a sarcoma, and this has possibly caused an 
error of diagnosis in some cases. As the two tumors arise from tissue of 
different natures and develop in different situations their combination 
is theoretically unlikely. 

Certain forms of tumors have been described that appear to spring 
from the adventitia of the blood-vessels. They consist of masses of 
cells usually sharply circumscribed, somewhat cylindrical in shape 
having in their center a small lumen in which blood-cells may some- 
times be detected. These are the so-called perithelioma or angiosarcoma. 
Such tumors in all probability come from the meninges in most cases. 

Fibroma occurs as a hard, circumscribed tumor, sometimes found 
in the hemispheres, but it is extremely rare. 

Lymphangioma appears to arise from the pia. 

Osteoma is usually an extension inward from the skull or mem- 
branes, but occasionally occurs as a tumor, apparently originating 
in the brain substance, forming hard masses from the size of a pea 
to that of a cherry, and somewhat irregular in shape. 




Fig. 469. — Psammoma, showing calcareous spicules and whorls. 



Psammoma. — This special term has been given to tumors con- 
taining calcareous granules. Occasionally circumscribed fibrous tumors 
containing calcareous granules are found in the brain substance, but these 
are extremely rare (Fig. 469). 

Carcinoma of the substance of the brain is invariably a metastatic 
growth. It appears either as small, round, circumscribed nodules, of 
firm consistency and pale color; or as larger, more or less infiltrating 
masses with softened interior. It usually replaces entirely the nervous 
tissue, either pushing it aside or destroying it, and gives rise, therefore 
to more or less pronounced secondary degeneration. Multiple metas- 
tatic carcinomatous growths, however, may exist in the brain without 
causing clinical symptoms. 



972 



A TEXT-BOOK OF PATHOLOGY 



THE CHOROID PLEXUS 

The choroid plexus consists of a plexus of vessels derived from 
the mesoblast, that are everywhere covered by a layer of cuboidal or 
columnar epithelium. Histologically, it consists of an inner layer of 
endothelial cells and an outer layer of epithelial cells, separated by a 
small amount of areolar fibrous tissue. The structure of the choroid 
plexus, therefore, bears a very close resemblance to the structure of the 
glomeruli of the kidneys, and, as it is obvious that the blood-vessels of 
which it is composed can have no nutritive function, excepting in so far 
as they supply the epithelium that covers them, it has been supposed 
that the choroid plexus is a secretory organ, its object being to secrete 
the cerebrospinal fluid. This theory is sustained by the facts that the 
cerebrospinal fluid differs in composition from the lymph, or from the 
fluid poured out in serous exudations, and that extracts of the choroid 
plexus will stimulate the secretion of the fluid in experimental animals. 
The choroid plexus probably also acts as a barrier to the entrance of 
toxic substances to the spinal fluid, for, while we know little of the passage 
of chemicals through it during health, it is reasonably certain that when 
it becomes damaged its permeability increases. (See cerebrospinal 
fluid, page 974.) 

Hypersecretion.- — In certain cases in which communication between 
the cavities of the brain and the exterior exists — as, for example, through 
the ethmoid plate of the nose — there is distinct hypersecretion of the 
cerebrospinal fluid. In a case described by St. Clair Thomson as 
much as a pint was discharged in twenty-four hours. In these cases, if 
for any reason the flow is checked, symptoms of intracranial pressure 
occur. Regarding the pathological changes in the choroid plexus that 
are associated with this condition we have at present no information. 
Hypersecretion probably also takes place in all inflammatory conditions. 

Inflammation. — In inflammatory conditions, particularly meningitis, 
encephalomyelitis, either separate or combined, and associated with the 
presence of an abnormal quantity of albumin in the cerebrospinal fluid 
more or less inflammation of the choroid plexus is usually found. This 
is indicated particularly by round-cell infiltration about the vessels 
and beneath the epithelium. Sometimes there is a slight amount of 
exudation upon the epithelial surface, and occasionally small foci of 
suppuration can be detected. 

Infectious Diseases. — Among the infectious diseases the only one 
of importance is tuberculosis. In this condition miliary tubercles or 
large cheesy foci are found. 

Chronic inflammation appears to be exceedingly rare, or, what is 
probably more accurate, has rarely been described, for there is every 
reason to believe that the choroid plexus shares in all conditions that 
involve the pia mater. Atheromatous conditions seem to be very 
infrequent, but a certain amount of thickening of the walls of the vessels 
may be observed in old age. A certain amount of overgrowth of con- 
nective tissue, sometimes associated with slight round-cell infiltration, 
is also occasionally found in old people. 

Hemorrhage may take place into the choroid plexus, and is usually 
an agonal phenomenon. 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



973 



Degenerations. — Calcification is the most frequent of the infiltra- 
tions. This may be recognized by the gritty sensation upon cutting 
into the choroid plexus. Microscopically, the calcareous nodules 
appear as minute dark granules that stain purplish with hematoxylin. 
Masses of cholesterin are by no means uncommon; they rarely present 
the form of typical cholesterin plates, but are somewhat irregular in 
outline, of a faint yellowish color, and shine brightly when examined by 
oblique light. Both conditions are common in old people. 

Pigmentary infiltration probably also occurs, certainly in malaria, 
and perhaps in old age. 

Ependymitis of ventricles may be chronic or acute. The acute 
form is always secondary to meningitis, and is characterized by prolifer- 
ation of the ependymal cells and the usual inflammatory changes. 




Fig. 470. — Sclerotic nodule in the floor of the lateral ventricle, with wrinkling of the 

ependyma; X 100 (Sailer). 

Chronic ependymitis is usually associated with sclerosis of the brain. 
The surface is granular or even nodular. The ependyma is thrown into 
folds, and there is great proliferation of the subependvmal neurogliar 
fibers (Fig. 470). 

Tumors. — A great variety of tumors occurs in the plexus. Cysts 
may be either retention or extravasation cysts, or parasitic. The 
retention cysts may be lined with epithelium, and probably represent 
adhesions at the edges of fissures with persistence of secretory activity. 
More commonly they are lined with endothelium and represent dilated 
lymph-spaces. They may be single or multiple, and appear as small 
translucent sacs, filled with a clear, slightly yellowish liquid, or else a 
colloid-like, viscid mass. Parasitic cysts are usually due to Tcenia 
solium. They may be either single, the Cysticercus cellulosa?, which may 
be attached to the plexus or lie free in the ventricular cavity, or multiple, 
forming the so-called Cysticercus racemosa of the brain. 

Among the benign tumors, fibromata, possibly only organized thrombi, 
and lipomata have been described. A dermoid cyst has been reported by 
Lebert. Endotheliomata may spring from the lymphatic spaces. Epi- 
theliomata, or ependymoma, may arise from the epithelial covering. 



974 



A TEXT-BOOK OF PATHOLOGY 



Two varieties have been described: the papillomatous and cylindrical 
cell tumor. These tumors are rarely uniform in character or pure in cell 
content; they are apt to show solid and cystic areas, and to contain 
some nervous tissue elements. They are usually single growths and 
do not give metastases. 

The cerebrospinal, or arachnoid, fluid is a clear, limpid, colorless 
liquid occupying the meshes of the arachnoid, the subdural space, 
and the free cavities of the central nervous system. The amount is 
variously given from 50 to 150 c.c, but only a small portion is obtained 
by spinal puncture. It is faintly alkaline in reaction and salty in taste; 
its specific gravity is about 1007, varying slightly in health and but 
little in disease, except when the liquid is distinctly purulent, it then 
being notably heavier. The fluid is produced by filtration through 
the choroid plexus and by the secretory power of this organ, by the peri- 
vascular tissue of the nervous system, and possibly by the arachnoid 
villi. The undamaged plexus is impervious to foreign substances 
coming via the blood unless they have the power to destroy the in- 
tegrity of the vascular wall: therefore drugs and therapeutic sera do 
not appear to any extent in the fluid. In disease on the other hand 
the permeability of the plexus and meninges is greatly increased. The 
cerebrospinal fluid returns to the circulation via the arachnoid villi, 
and by way of the veins and lymphatics around the vessels and cranial 
nerves. Its accumulation in disease is due to overaction of the sources 
by congestion and to obstruction to its escape by inflammatory lesions 
of the meninges. In health the fluid contains a small quantity of 
globulin, nucleoprotein, albumose, and urea; a reducing body is also 
usually present. Normal fluid contains no enzymes nor fibrin so that 
only pathological fluids show a coagulum. The cells of the fluid are only 
mononuclear, lymphocytic and endothelial, during health, and not over 
10 per cubic millimeter. The fluid, as determined by measurement 
in the spinal column, has a pressure of about 120 to 160 mm. of water 
when the person is recumbent; for the sitting position 50-75 mm must 
be added. It is lower in children than in adults. The functions of the 
cerebrospinal fluid are to act as a mechanical support and protection 
to the central nervous system, and it may be a medium of metabolic 
activity for the superficial parts of the brain, notably in the dissemination 
of pituitary secretion. 

In disease so many modifications are possible that only the most 
characteristic for the various important conditions can be given. So far 
as quantity is concerned, the only change seems to be in the direction of 
imcrease, a condition brought about by inflammatory lesions, decrease of 
blood-pressure, or to venous obstruction. Within the ventricles in- 
crease of the fluid and its pressure are caused by an obstruction to the 
passage of fluid from the ventricles through aqueduct of Sylvius and 
the foramen of Magendie. 

Cerebrospinal meningitis of the epidemic form shows in early stages a 
cloudy fluid, but soon a distinctly yellowish green purulent character 
is assumed. Cells up to many thousands per cubic millimeter are found. 
Micro-organisms are found within the cells and free in the fluid. Protein 
contents are naturally much increased. The pressure may rise to 



DISEASES OF THE BRAIN AND ITS MEMBRANES 



975 



several hundred millimeters of water. Meningitis of pneumococcus 
origin will give gray cloudy fluid with much fibrin, while in influenzal 
cases the fluid is opalescent and yellowish. 

Tuberculous meningitis gives, as a rule, an excessive, clear fluid in 
which a delicate coagulum will form on standing; occasionally the fluid 
is turbid. The pressure is quite high during early stages but later, 
especially at the time paralyses appear, it declines. Protein is in- 
creased about in proportion to the cellular content; mononuclears 
usually predominate, but polynuclears may be numerous. 

Paresis and Tabes. — In these conditions the amount of the cerebro- 
spinal fluid is usually increased, but not always, and the significant 
features are a pronounced increase in mononuclears and an excess of 
globulin. The fluid may also contain the antigen of syphilis and may 
be used in the Wassermann test . 

In psychoses the fluid is usually in excess but without characteristic 
cellular or chemical change. A toxic substance probably alcohol, has 
been detected in the spinal fluid of delirium tremens; there is also a 
decided rise in pressure. 

Poliomyelitis. — In the very early stages the fluid may be slightly 
turbid, but it shortly becomes clear; occasionally spontaneous coagula- 
tion with a very faintly cloudy clot is seen. Protein is increased early 
in the disease and usually remains in excess throughout the attack. No 
great excess of cells is found; polynuclears may be as numerous as mono- 
nuclears. The fluid in poliomyelitis is in great excess, and may be as 
high in pressure as in pyogenic inflammatory diseases. It rarely contains 
the virus. 

Trypanosomiasis gives an excess of clear or slightly turbid spinal 
fluid in which an increase of mononuclears and of the globulin may be 
found; the trypanosomes may also be present. In tricinosis the spiral 
parasite is said to be discoverable very early but it fails to rouse any 
chemical or cellular alterations. 

The Spirochceta pallida has been found in the fluid in cases of acute 
syphilis of the meninges, accompanied by a high lymphocytosis and 
moderate increase of pressure. 

In very many acute infectious disorders there are at times evidences 
of irritation of the meninges to which the term meningismus has been 
applied. There is usually a definite increase in amount and pressure 
of the fluid but no peculiar or characteristic cellular picture. In a 
general way the diseases associated with polynuclears in the blood, 
have it also in the fluid while a similar parallelism exists when lympho- 
cytosis is found in the blood. 

Hydrocephalus. — Excess in quantity of the cerebrospinal fluid in 
the ventricles is known as internal hydrocephalus. In practically all 
cases, in the absence of active inflammation, the fluid in this condition 
is normal in physical and chemical characters. It may be congenital 
and perhaps due to a malformation, but is more often a result of disease. 
Congenital hydrocephalus frequently appears to be due to some defect 
on the part of the parent, and is particularly common in the children 
of drunkards. 



976 



A TEXT-BOOK OF PATHOLOGY 



Congenital hydrocephalus internus is characterized by a gradual 
accumulation of cerebrospinal fluid in the lateral and third ventricles 
of the brain, probably the result of excessive secretion from the choroid 
plexus, with some anomalous formation to prevent its escape or ab- 
sorption (Fig. 471). As a general rule, the fourth ventricle is not in- 
volved. The aqueduct of Sylvius, however, is often dilated. Sometimes 
the fifth ventricle is distended or the septum has atrophied and dis- 
appeared, allowing free communication between the two lateral ventricles. 
Less frequently the infundibulum is distended and forms a small sac at the 
base of the brain. Usually the disease is manifest at the time of birth, 
and the head may even at this period have attained the circumference 
^ of more than 50 cm. Externally, the head 

is spherical and large; the face is small, 
and, with the bulging forehead, gives to these 
patients a characteristic expression. The 
cranial bones are usually more or less sepa- 
rated; frequently the edges of the sutures are 
an inch or more apart. The anterior fontanel 
is large and usually bulging. If the bones 
of such a skull be examined, it will usually 
be found that they are very thin and that 
ossification is incomplete. The dura mater 
is tense, and beneath it may be found the 
greatly flattened convolutions. The brain 
substance seems softer; often there is distinct 
fluctuation, although the brain collapses as 
soon as it is removed from the cranial cavity. 
The distance from the wall of the ventricle 
to the surface is much less than normal, this 
atrophy seeming to affect the white substance 
more than the cortex. The total weight of 
the brain, however, is often normal or nearly 
so, and it is impossible to say that an actual 
ternai hydrocephalus, with atrophy has really taken place. The substance 
marked atrophy of the white 0 f the brain is pale, probably as a result of 
substance (from Bollinger). ^ e pressure, and often softened, particularly 
in the neighborhood of the ventricles, although this is probably only 
an unusually rapid postmortem change. The floor of the ventricles 
may be smooth or slightly roughened, and occasionally distinct nodules 
may be observed. In the latter case there is usually considerable 
proliferation of the neuroglia in the cortex, and just beneath the floor 
of the ventricle a sort of sclerosis of the brain substance. The cerebro- 
spinal fluid is usually clear and not abnormal in consistency. Occa- 
sionally, however, it is somewhat turbid, particularly if there are any 
signs of old inflammatory action. The choroid plexus is often somewhat 
enlarged, pale, and may contain cysts. As the patients increase in age 
there is usually considerable increase in size of the head; nevertheless, 
the convolutions gradually become more rounded and the white sub- 
stance appears to undergo a sort of redevelopment, for the layer of 
brain tissue between the ventricle and the surface becomes thicker. 




DISEASES OF THE BRAIN AND ITS MEMBRANES 



977 



Systemic degenerations of the white fibers are uncommon. There 
may, however, be marked thinning of the corpus callosum and the 
anterior commissure. Cases have been described in which descending 
degeneration along the pyramidal columns was found in the cord. 

Partial hydrocephalus has been described. It is probably, in the 
great majority of cases, of congenital origin. It may affect only one 
ventricle, or even only a part of a ventricle, as, for example, the anterior 
or posterior horn of one of the lateral ventricles. It appears to be the 
result of an obliteration of one of the normal passages by which the 
ventricles communicate with one another. 

External hydrocephalus is the accumulation of fluid that occurs 
in the subarachnoid space to replace brain tissue that has undergone 
atrophy, or to fill the cavities in porencephaly. Occasionally sym- 
metrical collections of liquid are found, as in a brain removed from an 
idiot, in which both temporosphenoidal lobes were excavated and re- 
placed by large cysts. 

Acquired hydrocephalus may be either acute or chronic. The 
acute forms are usually secondary to inflammatory changes in the 
meninges, extending to the choroid plexus and to the ependyma, or are 
caused by some abnormal growth pressing upon the veins of Galen, 
or to obstruction of the aqueduct of Sylvius or the foramen of Magendii. 
In the atrophic brains of the aged dilated ventricles are frequently found. 

Acute acquired internal hydrocephalus is usually the result of acute 
basilar meningitis, either inflammatory or tuberculous. The brain, 
in addition to the changes in the meninges, presents all the character- 
istics of intense intracranial pressure. The convolutions are flattened 
and pale. The brain tissue is usually soft, or at least softens rapidly 
after death, particularly the part that surrounds the distended ven- 
tricles. Upon opening the brain the fluid is usually found under con- 
siderable pressure, and often almost gelatinous in consistency. 
Frequently, microscopical examination of the brain substance will show 
the presence of acute, disseminated, suppurative encephalitis. The ep- 
endyma of the ventricles is injected and often covered with lymph. 
In the tuberculous form it may be roughened, as a result of the presence 
of numerous miliary tubercles. The choroid plexus is injected; in the 
acute forms it also has some lymph upon the surface, and in the tuber- 
culous form may contain miliary tubercles. 

Chronic hydrocephalus is usually a late result of meningitis, particu- 
larly the epidemic form. Occasionally it is the result of gradual com- 
pression of the veins of Galen, or obstruction to the course of the liquid 
from the lateral ventricles to the subdural space, as for example, by a 
tumor of the cerebellum. Perhaps most frequently it is the result of 
a chronic, granular ependymitis. In these cases the distention is more 
pronounced than in the acute form. The ependyma is thickened and 
opaque, and often contains small hard nodules. Occasionally, bands 
of organized fibers may be found in the cavity of the ventricle. 



62 



CHAPTER XIII 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 

The Dura Mater 

Diseases External to the Dura Mater. — Among the minor proc- 
esses that may occur externally to the spinal dura mater is fatty infil- 
tration, sometimes associated with general obesity, but occasionally 
found in patients that are moderately emaciated. , 

Hemorrhage may occur on the external surface of the dura, the 
blood being found distributed in the extradural areolar tissue. The 
usual cause is traumatism, but it may also occur in convulsive condi- 
tions. Ordinarily, the blood remains circumscribed and forms a spinal 
hematoma; rarely, a cyst results. 

Diseases of the Dura Itself. — Most of the pathological processes 
are secondary to some disease of the vertebral column. The most 
important is tuberculosis; this gives rise to external tuberculous pachy- 
meningitis, characterized by a collection of cheesy material which may 
have undergone either softening or necrosis, or else contains pus-cells. 
The dura in the affected region is usually considerably thickened, and 




Fig. 472. — Tuberculous pachymeningitis secondary to spinal caries. 

may have upon its inner surface a slight amount of exudate. The char- 
acter of the lesions is not different from that of tuberculosis in other 
serous membranes (Fig. 472). 

Pachymeningitis cervicalis is a localized tuberculosis or syphilis 
of the dura mater occurring in the cervical region, and characterized 
by considerable thickening, sometimes amounting to % cm. or more. 
The dura is usually adherent to the spinal canal and to the arachnoid 
and pia, the latter showing more or less involvement. The serious 
changes consist of compression of the roots and of the spinal cord, the 
latter especially in the anteroposterior direction. The process may 
extend into the substance of the cord and produce a myelitis of the 
periphery, and occasionally extends deeper and causes more or less 
extensive secondary degenerations. 

Of the acute inflammations the most important is internal hemor- 
rhagic pachymeningitis, a process similar to that occurring in the dura 

978 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 979 

mater of the brain. It consists of a layer of granulation tissue in which 
many of the capillaries have ruptured, giving it a more or less uniform 
reddish appearance; it is somewhat irregular in outline and of varied 
extent, and not infrequently adhesions form between the dura and the 
arachnoid. 

Syphilis occurs either in the form of discrete gummata or as a regular 
and diffuse thickening of the inner layer. 

Tumors of the dura are rare, but when present grow inward, com- 
pressing the cord and giving symptoms of transverse localized disease. 
Tumors from the spinal canal frequently invade the dura. 

Lipoma is the commonest benign tumor. Myxomata and fibromata 
are exceedingly rare. Chondroma has been observed. 

Sarcoma may be of the round-cell, angiomatous, or alveolar type. 
It is usually irregular in outline, spreading like a fungous mass over 
the surface of the membrane, which exhibits fibrous thickening. If 
small and occurring on the anterior aspect, it may produce no symp- 
toms whatever. In this situation it is frequently secondary. In a 
few rare instances melanotic sarcoma has been observed. Not in- 
frequently a granular sarcomatous mass invades the cauda equina 
and infiltrates it for a considerable distance downward. The nerve- 
roots often fail to show any signs of degeneration, and apparently no 
pressure symptoms are produced. In some cases sarcomata of the dura 
produce proliferation of the neuroglia tissue in the adjacent portion 
of the spinal cord. 

Secondary tumors from the intestines or skeleton are occasionally 
seen in the dura. In rare cases echinococcus cysts have been observed 
and even the cysticercus. 

THE PlA-ARACHNOID 
CIRCULATORY DISTURBANCES 

Active hyperemia precedes and accompanies inflammatory changes. 
It is rarely seen postmortem, and in the majority of cases its existence 
can only be inferred. 

Passive hyperemia is very common — that is to say, in many 
cases the veins of the pia mater are found to be tortuous and greatly 
distended with blood. This is usually due to postmortem hypostasis. 

Hemorrhage may occur from traumatism or the rupture of small 
aneurysms, the most frequent place for the latter being the cervical or 
basilar region. 

DEGENERATION 

Calcareous infiltration sometimes occurs, appearing as small, 
hard plates, rarely more than 0.5 cm. in diameter, scattered along the 
whole length of the spinal cord. It is probably always secondary to 
inflammatory processes, as spinal syphilis and tuberculosis. 

INFLAMMATIONS 

Acute inflammation or acute leptomeningitis, is often second- 
ary to cerebral meningitis. It may occur, however, independently as 
a result of local suppurative processes, particularly those of the spinal 



980 



A TEXT-BOOK OF PATHOLOGY 



column. It may be serous or purulent in character, and in the latter 
an exudate is found upon the inner surface of the dura and in the sub- 
arachnoid space, often extending the entire length of the spinal cord. 
The microscopical changes are essentially similar to those found in the 
membranes of the brain. Involvement of the cord is, however, much 
more common. There is usually extensive round-cell infiltration in the 
anterior commissure and small foci of round cells scattered throughout 
the gray and the white matter, especially in the latter. Frequently 
these can be seen to surround a blood-vessel, but this is not always the 
case, and it is not unlikely that purulent material can enter from the 
lymphatics of the pia. The covering and interstices of the nerve-roots 
are commonly infiltrated. If death does not occur, adhesions may form 
between the dura and arachnoid, but these are certainly exceedingly 
uncommon in the cord. 

Chronic leptomeningitis is usually associated with sclerosis of 
the spinal cord; thus, in locomotor ataxia the pia mater over the poste- 
rior column may be opaque and slightly thickened. It may also be 
consecutive to some of the other inflammatory processes, and in this 
form adhesions may be found between the dura and arachnoid (pachy- 
meningitis and arachnitis adhesiva). 

In cases of injury of the spinal column, such as fracture, caries, etc., 
in which continuous pressure is produced upon the dura mater, it be- 
comes thickened and adherent to the bone and to the pia and may 
cause pressure upon the spinal cord. In these cases there is rarely any 
round-cell infiltration in the thickened dura, which consists almost en- 
tirely of fibrous connective tissue and blood-vessels; the latter have 
greatly thickened walls. 

INFECTIOUS DISEASES 

Tuberculosis may occur in the form of miliary nodules or as small 
cheesy masses, usually extending a slight distance from the pia mater 
into the substance of the cord. It is disputed whether an acute lepto- 
meningitis without miliary or cheesy nodules may be caused by this 
organism alone, but, while it is probable that such inflammation may 
occur, this has not as yet been definitely established. Solitary tubercles 
may occur in any part of the spinal cord. They are rarely encapsulated. 
Tuberculous meningitis is hematogenic, or arises by extension. The 
localized form is commonly the result of Pott's disease. A generalized 
form occurs in connection with cerebral meningitis (q. v.) . 

Syphilis appears as a thickening of the membranes with multiple 
gummata, often projecting into the substance of the cord or extending 
to and involving the dura mater. The vascular changes are very char- 
acteristic; nearly all the blood-vessels exhibit the typical round-cell 
infiltration and thickening of the intima which have been described in 
the section on endarteritis syphilitica. There are also a perivascular 
round-cell infiltration and some proliferation of the adventitia. The 
veins may also be involved. The lumen of both sets of vessels is usually 
contracted, and there is a great tendency to the formation of thrombi. 
In these thrombi organization may take place, with the formation of 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



981 



new blood-vessels. The spinal cord may also exhibit various lesions, 
due either to pressure or to direct extension inward from the pia. 

In congenital syphilis the upper part of the spinal cord appears to 
be more involved than the lower part. In syphilitic leptomeningitis 
there are often extensive degenerations of the tracts in the cord. These 
involve particularly the lateral and posterior columns, giving rise to a 
combined sclerosis; and, in addition, there is often a narrow band of 
sclerotic tissue encircling the cord and lying immediately beneath the 
pia. 

Tumors of the pia are principally angiomata, endotheliomata, and 
fibromata; sarcoma and degenerative tumors like myxoma may occur. 
Neurofibroma, chiefly near the nerve-roots, is reported. Secondary 
tumors are carcinoma, sarcoma, and myeloma. They produce symp- 
toms like those noted under the dural tumors. 

ANATOMY OF THE CORD 

The spinal cord is composed, as are the other parts of the central nervous system, 
of gray and white matter, the gray matter occupying the central part and the 
white matter being distributed around it. The cord is of varying size, somewhat 
broader and flatter in the cervical region than elsewhere ; almost circular in the dorsal 
region, and again thicker in the lumbar region. It communicates with the rest of the 
body by means of the spinal nerves, which arise anteriorly and posteriorly as roots. 
It is surrounded by three membranes; the pia, adherent to it; the arachnoid, adherent 
to the pia, but not dipping into the anterior fissure, and the dura mater, which is 
adherent neither to the arachnoid nor to the vertebral column. The gray matter 
is divided into two parts by the anterior commissure and posterior septum, each part 
consisting of an anterior horn, a thick, roundish mass, and a posterior horn, a slenderer 
projection. The lateral halves are united by the gray commissure, in which is the 
central canal lined with cuboidal epithelium and continuous with the fourth ventricle 
above. In the anterior cornua are found the large multipolar ganglion-cells, whose 
axis-cylinders pass out through the anterior roots and end in the muscles; commenc- 
ing in the dorsal region, there is a group of cells in the inner portion of the posterior 
horn, near the gray commissure, which are bipolar and whose axis-cylinders pass 
outward to the cerebellar tract, in which they ascend to the vermiform process of the 
cerebellum. The posterior roots are composed of fibers that originate in the spinal 
ganglia and pass into the cord. These spinal ganglion-cells have a single process, 
which appears to divide into two fibers, one passing outward into the peripheral nerves 
and usually terminating in the sensory corpuscles of the skin, the other passing inward 
through the posterior root to the spinal cord. The white substance of the spinal cord 
is composed of bundles of nerve-fibers that have, for the most part, a common func- 
tion, a common mode of origin and of termination. 

Anatomically, the cord may be divided into three regions: anterior, lateral, and 
posterior, although these do not correspond to regions embryologically distinct. 
According to the manner of development, it should be separated into the anterolateral 
and the posterior regions. 

The most important bundles of fibers in the anterolateral columns are those known 
as the pyramidal tracts, for the reason that they are continuations of the pyramids 
of the medulla. They originate in the motor region of the cerebral cortex and, in the 
first cervical segment, decussate through the representatives of the anterior cornua to 
reach their situation in the lateral columns. This decussation does not occur in all 
of the fibers, many passing down in the direct pyramidal columns and some with- 
out decussation in the lateral columns. These undecussated fibers subsequently 
cross to the other side through the anterior or white commissure. The fibers of the 
pyramidal columns terminate in arborizations which surround, but are not in contact 
with, the ganglion-cells of the anterior cornua. 

The cerebellar tract has already been described. Anterior to it and close to the 
periphery of the cord is the so-called anterolateral column of Gowers. The fibers which 



982 



A TEXT-BOOK OF PATHOLOGY 



form this probably originate in the lateral groups of cells in the anterior cornua and 
in the cells in the middle portion of the spinal cord. The column increases in size 
upward and degenerates in the same direction. It also contains fibers that 
degenerate downward, of whose origin and termination we are ignorant. 

The rest of the anterolateral column is composed of short fibers, uniting different 
segments of the spinal cord. 

The posterior columns are composed of the fibers that enter by the posterior 
roots. These fibers divide into two branches, one ascending and the other descend- 
ing, the latter terminating in the gray matter of the posterior horn. The ascending 
fibers may be divided into two groups, the lateral and median bundles. The fibers 
of the lateral bundle are somewhat finer and evidently belong embryologically to a 
different period, because they acquire their myelin-sheaths later. They pass directly 
into the zone of Lissauer, and thence into the substantia gelatinosa of Rolando, 
and some of them terminate in arborizations about the ganglion-cells in the column 
of Clarke. The fibers of the median bundle are coarser. They pass inward, then 
upward along the inner side of the posterior horns, and then become the column of 
Burdach. The median fibers from the lower part of the cord bend inward and con- 
tinue their course in the column of Goll, terminating finally in the nucleus gracilis 
of the medulla oblongata. The fibers that enter the cord in the cervical region pass 
upward in Burdach's column and terminate in the nucleus cuneatus. Other fibers 
pass forward to the ganglion-cells of the anterior cornua, and have been supposed to 
be concerned in reflex action. Others decussate in the posterior commissure and 
then pass upward in the posterior columns of the opposite side. At somewhat regular 
intervals they give off at right angles fine collateral branches, which pass forward, 
and some of them, at any rate, end in arborizations about the cells of the anterior 
cornua of the gray matter. These are known as the reflex collaterals of Kolliker. 
A small portion of the posterior column just back of the gray commissure appears 
to be composed of fibers uniting the different segments. Physiologically, the spinal 
cord may be regarded as a series of superimposed centers which contain cells sending 
or receiving impulses to or from the periphery, and bands of fibers that unite these 
centers with the brain. The functions of these different tracts have already been 
discussed in the Anatomy of the Brain. An important function of the spinal cord is 
the accomplishment of reflexes. The centers for these reactions are situated in various 
portions, and according as these portions are intact or involved the reflexes persist 
or disappear. By means of the distribution of the sensory and motor disturbances 
and the alterations in the reflexes, accurate localization of a lesion in the cord is 
often possible. 

The lymph-channels of the cord are of some importance in inflammations by 
continuity. The conclusions of Bruce and Dawson upon their anatomy indicate 
that they follow the adventitia of the capillaries, veins, and arterioles toward the 
surface of the cord where they enter the deep layer of the pia, through which they 
probably communicate with the subarachnoid space. "The lymphatic path has 
in the main an outward direction, but there is no doubt that it permits of a current 
inward, or of an invasion by cellular elements, micro-organisms, and toxic substances." 

CONGENITAL ABNORMALITIES 

Total absence of the cord, or amyelia, only exists in associ- 
ation with anencephalus. It is interesting to note that the spinal ganglia 
usually persist. 

Abnormal smallness is known as micromyelia. The cord may 
be normal in structure, all the elements being proportionately reduced, 
but more commonly only certain parts are affected, particularly the 
pyramidal columns, as a result of fetal lesions in the motor tract. 

Double cord or diastematomyelia, is usually localized to one 
portion of the cord, particularly the lumbar region. Occasionally the 
cord is completely divided by a bony septum. In this case the gray 
matter in either half presents the normal arrangement of the gray matter 
in the cord. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



983 



Unusual length of the cord may also occur, the conus terminalis being in these 
cases elongated and extending to the end of the sacrum. The spinal roots may be 
excessive or defective in number on one or both sides. This usually occurs in the 
dorsal region, the commonest condition being the presence of eleven roots on one side. 
The cord may be asymmetrical. This usually involves only the pyramidal columns, 
and is due to incomplete decussation. 

Heterotopia of the gray matter is not infrequent. This may con- 
sist of doubling of one of the horns, abnormal relation of gray and white 
matter, disorganization of one or both horns, or fissures extending into 
the substance. According to van Giessen, the majority, if not all, of 
these cases are the result of injury during removal, and are therefore 
to be regarded as artefacts. This statement is, however, too sweeping. 
Abnormal bundles, producing heterotopia and due to alterations in the 
medulla or even higher in the central nervous system, have been found. 
These appearances may also be produced by tumors or other conditions 
causing pressure. 

Dilatation of the Central Canal. — The central canal may be 
dilated, either locally or throughout its whole length. This condition 
is known as hydromyelia, or hydrorrhachus, and is akin to hydrocephalus, 
with which it is sometimes associated. Hemorrhage may take place 
into these dilated canals and gives rise to hematomyelia (vide infra) . 

Localized collections of liquid in the subarachnoid spaces are some- 
times spoken of as hydrorrhachus externa. 

Spina Bifida. — There may be imperfect closure of the posterior 
processes of the vertebrae, giving rise to clefts, which are known as 
rachischisis. If the membranes of the spinal cord protrude through 
the cleft in an imperfectly closed canal in the form of a sac or hernia, 
the condition is called spina bifida. In some cases the skin is still present 
and is often covered by an abnormally thick growth of hair. In other 
cases the dura or this membrane fused with the pia may be the only 
membrane that enters into the formation of the wall. The membranes 
are- usually thickened, and may be covered with granulations. The 
spinal cord may be normally formed and hang in the sac or be split or 
compressed. Sometimes the dilatation evidently takes place in the 
central canal, for the substance of the spinal cord may be recognized 
adhering to the inner layer of the pia mater. This condition is called 
myelomeningocele. Spinse bifidse usually appear, in the sacral or lower 
lumbar region, although rachischisis may involve the entire length of the 
vertebral canal. Rarely a cystic dilatation of the meninges may take 
place between completely formed vertebral arches. 

HYDROMYELIA AND SYRINGOMYELIA 

Hydromyelia is a condition in which the central canal of the spinal 
cord is dilated. It frequently occurs in circumscribed portions and is 
apparently without clinical significance. More rarely the whole canal 
has a macroscopical lumen throughout its entire length, particularly 
in cases of hydrocephalus, although in the majority of cases of this latter 
disease the spinal cord is not involved. A patulous canal can be distin- 
guished from a pathological cavity by the fact that the canal is lined by the 
normal cuboidal epithelium of the ependyma. Usually there is a con- 
siderable collection of ependymal cells in the neighborhood of the central 



984 



A TEXT-BOOK OF PATHOLOGY 



canal, and this is more apt to be the case if it is dilated or otherwise 
altered than if it is normal. Occasionally the central canal is doubled. 
This rarely happens throughout the whole length of the cord, but is more 
frequently found in a limited portion, especially the lumbar region. 
This doubling is due in some instances to the obliteration of the central 
part Of a dilated canal with its long axis transversely placed. Sometimes 
a slit-like canal shows a dilatation in only one part. At places the lumen 
of the canal may be completely obliterated, leaving nothing but a mass of 
cells in the gray commissure, in the midst of which capillaries may be 
observed. More distinct pathological changes are diverticula that 
occasionally spring from the canal. These seem to be most frequent in 
the cervical and dorsal regions. They usually extend downward, and are 
situated posteriorly to the gray commissure. It is possible that collec- 




Fig. 473. — Hydromyelia (partly diagrammatic). 

tions of epithelial cells from the ependyma under similar circumstances 
may form masses in the posterior column without distinct cavity form- 
ation, although this is doubtful. These changes are particularly signifi- 
cant on account of their relation to the disease known as syringomyelia 
(Fig. 473). 

Syringomyelia. — Pathologically, this is essentially a cavity' in the 
spinal cord that is not lined throughout with the columnar epithelium 
of the ependyma. This cavity may appear as a wide dilatation or as a 
narrow slit. It usually occupies the posterior part of the cord is exceed- 
ingly asymmetrical, sometimes limited entirely to one side, and in these 
cases is ordinarily found in the posterior horn or on its inner side. The 
cord may be unaltered externally. The dura mater is commonly normal. 
The pia and arachnoid are either normal or else thickened slightly, the 
changes being not unlike those found in senility or in cases of chronic 
edema of the membranes. The shape of the cord may be entirely 
normal. This, however, is rare. Usually there is some asymmetry, 
and frequently, particularly if the cavity be large, the cord upon being 
removed and laid upon a flat surface seems to collapse, giving rise to 
the so-called ribbon appearance. Section through the cord shows the 
existence of a larger or smaller cavity filled with the products of lique- 
faction-necrosis, cerebrospinal fluid, or more rarely with blood. Some- 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



985 



times it appears to have been empty, in which case the cord 
probably was collapsed in the spinal canal and the space thus formed was 
filled with cerebrospinal fluid. The solid portion of the cord is usually 
somewhat darker in color, and the distortion of the outline corresponds 
to the extent of the process. The portions of spinal cord not involved 
by the lesion, and below it, commonly show more or less descending 
degeneration. In the portion above the cavity, if it does not extend 
as far as the medulla, some degeneration in the posterior columns is 
often found. In many cases, however, both ascending and descend- 
ing tracts are intact; at least they appear so to the naked eye. Micro- 
scopical examination shows that the cavity is bounded, as a rule by a 
delicate reticulum of hyperplastic neuroglia. Sometimes this is lined 
with what appears to be connective tissue, and is supposed to be an inclu- 
sion of the pia mater; at other times it is lined with ependymal epithe- 
lium. The tissue in the neighborhood is usually hyperplastic neu- 
roglia. The cord in the immediate neighborhood may show curiously 
few changes, the ganglion-cells being perfectly normal and the fibers 
uninjured. If the cavity is extensive and the proliferation of the neu- 
roglia considerable, this is not the case. An entire posterior root may 
be destroyed, or perhaps half or more of the spinal cord will be exten- 
sively degenerated; in these cases secondary degeneration always occurs. 
Not only the pyramidal tracts, but also bundles in the posterior columns 
degenerate downward. In a case that was studied by one of us the 
comma tract of Schultze was beautifully outlined. The nerve-roots are 
also usually involved, and there is descending degeneration along the 
anterior roots, which may be detected also in the nerves. The poste- 
rior roots may show some degeneration, but this is rare and the cells of 
the spinal ganglia are usually intact. Sometimes there is considerable 
vascular proliferation in these portions of the cords not unlike cavernous 
change. There is at times so active a gliosis that a suspicion of glioma- 
tous or sarcomatous change has arisen; the seat of this change is char- 
acteristically in the tissue in the vicinity of the central canal. 

As syringomyelia is particularly a disease of the central portion 
of the spinal cord, the fibers that convey pain and temperature sense 
are essentially involved, and, as a result, one of the characteristic 
changes is the dissociation of sensation — that is to say, persistence of 
tactile sensation with thermo-anesthesia and analgesia. In addition, 
as the cells of the anterior cornua are involved, there is degeneration 
in the muscles that they supply. 

The most widely accepted theory for the origin of this condition is that the process 
is one of gliosis arising from the ependyma of the central canal, since glia tissue is in 
all probability the descendent of ependyma. This proliferation of the ependyma 
and metaplasia to glia tissue is assisted by congenital malformation and vascular 
conditions of congenital or inflammatory nature. The softening proceeds within 
the areas of glia proliferation by pressure and lowered nutrition. Conditions favor- 
ing hydromyelia will, therefore, predispose to syringomyelia. 

CIRCULATORY DISTURBANCES 

Diseases of the walls of the blood=vessels are similar to those 
occurring in the blood-vessels of the other parts of the body. Exten- 
sive atheromatous changes are relatively rare. Perhaps the most fre- 



986 



A TEXT-BOOK OF PATHOLOGY 



quent disease is hyaline degeneration, which is exceedingly common in 
cases of sclerosis, and may occur in early life, even in childhood. It is 
almost invariably present in the cords of persons dying after middle life. 

Attention has been directed more particularly to these changes 
on account of the suggestion by Redlich that they are the anatom- 
ical basis of paralysis agitans. According to him, the character- 
istic changes are endarteritis and periarteritis, with extension of the 
latter process into the surrounding nerve substance and the formation 
of perivascular insular scleroses. In addition, there is often some 
degeneration in the posterior columns and, occasionally in the lateral 
columns in the cervical and lumbar enlargements. The vascular 
changes, curiously enough, appear to be more severe in the posterior 
horns than in the other parts of the cord, and amyloid bodies are nearly 
always present in these regions. However, in examining the cord of a 
typical case of paralysis agitans one of us failed to find these lesions, 
while in another case, equally characteristic clinically, they were quite 
pronounced. 

Miliary aneurysms are very infrequent in the spinal cord. Aneu- 
rysms of the vertebral arteries, however, sometimes involving the com- 
mencement of the spinal branches, have been reported, but are rare. 

Active hyperemia of the spinal cord is rather a clinical hypothesis 
than a pathological entity. Occasionally, however, the gray matter 
seems to be slightly darker than normal, and there is rather free bleeding 
from the vessels cut transversely. In many cases of myelitis the arteries 
and capillaries may be found distended with blood. 

Passive hyperemia is more readily detected in the veins of the 
membranes than in the cord itself. 

Anemia is an important and easily recognized condition. Experi- 
mentally, it has frequently been produced by ligation of the abdominal 
aorta. Cases have occasionally occurred in human beings in which 
this vessel was occluded by a thrombus, giving rise to similar changes. 
The cord, under these circumstances is somewhat swollen, pale, and 
soft; not invariably, however, for cases have been reported in which 
microscopically it was entirely normal. The ganglion-cells, particularly 
those of the anterior cornua, are most distinctly affected. They exhibit 
usually the characteristic features of chromolytic degeneration. Similar 
changes may occur in other portions of the cord, but are exceedingly 
rare, partly on account of the free anastomosis of the blood-vessels, 
partly because if, as sometimes happens, thrombi are formed in the 
vertebral arteries, death occurs before characteristic changes have had 
time to develop. 

Varicose Veins. — Occasionally a group of vessels in one part of 
the spinal cord will be dilated and varicose, forming a sort of plexiform 
angioma. Anigomatous formations are frequently observed in various 
forms of myelitis and sclerosis. 

Hemorrhages may be of two kinds : punctate and massive. 

Punctate hemorrhages are really nothing but pericapillary exudations 
of blood-cells, which can readily be distinguished from the drops of 
blood that form at the cross-section of blood-vessels by the fact that 
they cannot be washed off. It is probable that if death does not occur 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 987 

at once they are in great part absorbed, leaving perhaps a minute scar 
that may be readily overlooked. These minute hemorrhages are per- 
haps more common in the cervical region than elsewhere. They are 
found in the course of infectious diseases, particularly those affecting 
chiefly the nervous system, such as tetanus, and especially hydrophobia. 
Small agonal hemorrhages into the substance of the spinal cord, particu- 
larly in the region of the central canal, are not uncommon. Occa- 
sionally these may be visible to the naked eye; they are, of course, to 
be distinguished from antemortem changes by the regular form of the 
blood-cells and the absence of blood-pigment. They are only impor- 
tant on account of the possibility of their being mistaken for patho- 
logical changes. 

Massive hemorrhages may be infiltrating or circumscribed. In the 
former the blood is found between the nerve-fibers and in the meshes 
of the neuroglia. The nerve substance is usually more or less degener- 
ated, and the lesion corresponds anatomically to the hemorrhagic infarct, 
Circumscribed hemorrhages are usually small when compared to those 
in the brain, a circumstance due, of course, to the restricted area in 
which they can occur. 

They do damage, of course, at once, by the separation of the fibers 
and cells; the greater damage, however, results from the pressure of the 
clot within the closely attached meninges. If the meninges be opened, 
thus relieving the tension, degeneration is much less apt to occur. 

The most common cause of this form of hemorrhage is traumatism 
and it may sometimes occur as a result of concussion without fracture 
of the spinal column. Hemorrhages may also occur in persons with 
diseased arteries as a result of violent effort or emotional disturbance. 

The clots are usually irregularly oval in outline, and are often sur- 
rounded by hyperplastic neuroglia, in the midst of which are found 
compound granular cells, and more or less degenerated nervous tissue. 

In the later stages the formation of fibrous tissue is apparent; capil- 
laries may also be found bending into the substance of the clot, which 
eventually is absorbed, leaving a scar that nearly always contains some 
pigment surrounded by coarse-meshed neuroglia tissue. Rarely the 
pigment is absorbed and a cyst remains limited by hyperplastic glia 
tissue; this lesion may form cavities along the cord and has been called 
false syringomyelia. Occasionally the hemorrhagic focus is restricted to 
the gray substance, the blood being found in cylindrical masses. This 
arrangement is due to the fact that in normal circumstances the gray 
matter is softer than the white, and offers less resistance to the extra- 
vasation of the blood. In this case the infiltrated area soon becomes filled 
with granular cells, the nerve-fibers degenerate, and crystals of hem- 
atoidin appear. 

Hematomyelia. — If the central canal is dilated and contains blood 
the conditions is known as hematomyelia. This may occur as the result 
of traumatism or because of some vascular degeneration. The latter 
form is occasionally associated with syringomyelia, and is found most 
frequently in the cervical portion of the cord. If the hemorrhage 
occurred some time before death, the only traces that persist will be 
discoloration of the ependyma, and perhaps the adjacent tissue. Hemor- 



988 



A TEXT-BOOK OF PATHOLOGY 



rhage may also occur during the death agony, in which case the central 
canal may either be filled with normal blood-cells, or, if it is at all 
dilated, there will be a thin layer of blood-cells upon the surface. The 
most common situation is at the point where the central canal opens into 
the fourth ventricle. 

INFLAMMATION 

Myelitis in the strict sense, is a term signifying an inflammation 
of the substance of the spinal cord. According to this view, it should 
be limited exclusively to forms of spinal disease secondary to hemato- 
genous infection, extension from the pia, or possibly extension from the 
central canal, although the latter can be dismissed as an unknown 
variety. The name has been used, however, to signify any form of 
softening that may occur, whether it be produced by injury or disease 
of the spinal column, by tumors, or by poisons circulating in the blood. 
It has also been applied to secondary changes the result of meningitis 
and to obscure lesions that either commence with a proliferation of the 
neuroglia, or as a primary degeneration or atrophy of the nerve sub- 
stance and secondary increase in the neuroglia tissue. According to the 
distribution of the lesions, myelitis is spoken of as circumscribed, trans- 
verse, or disseminated. 

Hematogenous Purulent Myelitis. — As a rule, the membranes of 
the brain are also infected, and show the characteristic. appearances of 
acute leptomeningitis, with subarachnoid accumulations of pus and 
injection of the vessels. Cross-section of the cord shows here and there 
small reddish or yellowish areas distributed irregularly throughout the 
cord; in longitudinal sections these usually appear as streaks following 
the course of the blood-vessels. The cord often seems to be softer and 
may be darker than normal. The microscopical changes consist of 
accumulations of pus in the pia mater and distention of the vessels, the 
presence of a perivascular round-cell infiltration, slight degeneration of 
the nervous tissue in the neighborhood of the lesions, and alteration of 
the neuroglia, which may show some looseness of its fibers. Alterations 
may be seen in the ganglion-cells, which consist chiefly of irregularity 
in the arrangement of the chromophilic bodies and perhaps somewhat 
diffuse staining. Should, however, ganglion-cells he in the midst of, or 
very close to, the purulent focus, they show a severer type of degenera- 
tion and often lose their protoplasmic processes- In these cases micro- 
organisms are not infrequently found. 

Myelitis secondary to purulent leptomeningitis is not greatly dis- 
similar from this, excepting that there is generally a more marked degen- 
eration in the periphery of the cord. These lesions have been observed, 
particularly by Councilmann, in epidemic cerebrospinal meningitis. 

Transverse myelitis, without local foci, secondary to injury or infec- 
tious disease — that is, the condition generally denominated myelitis — 
presents three stages — the stage of red softening, of yellow softening, and 
of gray degeneration. In the first the membranes of the cord are usually 
somew r hat opaque. The substance of the cord itself may be either 
swollen or shrunken, and is softer than normal in consistency. Upon 
section of the cord the surface is seen to be pink, and there may be 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 989 

minute hemorrhages; the tissue swells so that the surface of the cross- 
section is slightly convex. Microscopically, the most characteristic 
feature is the congestion of the blood-vessels; this is more marked in the 
veins than in the arteries. . There is usually a considerable amount of 
perivascular cellular exudate, the majority of these cells being poly- 
nuclear leukocytes. The myelin-sheaths show here and there degen- 
eration; the axis-cylinders are swollen, granular, and somewhat shrunken. 
The neuroglia cells are sometimes swollen, sometimes irregular in out- 
line and increased in number. The neuroglia fibers in the neighborhood 
of the vessels form a loose, irregular network. The ganglion-cells show 
pronounced alterations, usually similar to those already described as 
occurring in intoxication, such as irregularity in staining, peripheral 
situation of the nucleus, and varicosity or fragmentation of the proto- 
plasmic processes. If the process has lasted any considerable time, the 
most characteristic feature of myelitis, namely, the accumulations of 
granular cells, begins to take place. It is not certain what these cells 
are, but in all probability they represent the wandering connective- 
tissue corpuscles that have absorbed the granular fatty detritus of the 
myelin fibers. Occasionally, hyaloid bodies are present, even in con- 
siderable numbers. In the next stage a pressure-anemia begins to be 
apparent. A cross-section through the freshly removed cord shows that 
it is still somewhat swollen; the color is yellow. The distinction between 
the gray and the white matter is preserved, but the gray matter is dis- 
tinctly shrunken. Microscopically, the blood-vessels are shrunken; 
the perivascular cellular exudate is still present, but many of the cells 
contain fat-droplets. Throughout the whole cord are found compound 
granular cells, giving to it a peculiar and characteristic appearance. 
The nerve-fibers are swollen, granular, or shrunken. The myelin-sheaths 
are filled with droplets of fat, or have partially disappeared. The 
neuroglia may be still looser in its texture. The neuroglia cells are 
more apt to show degenerative changes. In this stage the alterations in 
the ganglion-cells are those of the most pronounced degeneration. In 
the severest grades of this condition the substance of the cord has under- 
gone liquefaction and is reduced to a puriform mass, which it is impossible 
to examine, excepting upon films. It is then found to contain fat-drop- 
lets, granular cells, and detritus. In the stage of gray degeneration there 
is a secondary distention of the blood-vessels, giving it a somewhat redder 
appearance. There is proliferation of the connective tissue, which has 
a tendency to retract and cause concavity of the surface of the section. 
The granular cells are found chiefly in the neighborhood of the blood- 
vessels. The neuroglia tissue is looser and appears to enclose numerous 
vacuoles. The nerve-fibers have in large part disappeared, although a 
few show degenerative changes, and the ganglion-cells are reduced to a 
few masses of pigment or else have disappeared entirely. By this time 
secondary degenerations usually begin to appear above and below the 
lesion, particularly in the sections stained by Marchi's method. 

Pressure-myelitis. — The alterations produced in the cord by slowly 
developing pressure, such as the growth of a tumor in the membranes, 
or gradual bending of the spinal canal, as in Pott's disease, produce 
somewhat characteristic changes. The cord at first becomes anemic, 



990 



A TEXT-BOOK OF PATHOLOGY 



due to the mechanical occlusion of blood-vessels in the affected seg- 
ment. As the pressure increases and the anemia continues degenerations 
ensue in the white matter. These are accompanied by the appearance 
of a moderate number of granular cells and by slight proliferation of 
the neuroglia. It appears that this degeneration affects first the myelin- 
sheaths, and that the axis-cylinders may maintain their vitality for a 
considerable length of time, for regeneration has occurred after the 
cord has been considerably reduced in size by long-continued pressure. 
The gray matter appears to persist for a longer time. This does not 
mean that the ganglion-cells remain absolutely intact, for in the early 
stages of the process they exhibit various degenerative changes. As we 
already know, however, such degenerative changes are not necessarily 
fatal to the vitality of the cell. Later, they begin to shrink, usually 
becoming at first darker, then losing their protoplasmic processes, and 
ultimately undergoing change into small irregular vesicles that are 
frequently pigmented. The neuroglia gradually proliferates, and 
ultimately the cord is converted into a sclerotic mass at the point of 
pressure. This mass is gray in color, seems dry, and often in the process 
of hardening develops numerous irregular fissures. The central canal 
is variously affected. It may be, at different levels, obliterated, dilated, 
doubled, or even tripled. This appearance of doubling or trippling, 
however, is due to the extrusion of diverticula, which pass upward or 
downward more or less parallel to the axis of the cord. The epithelium 
lining the central canal maintains its vitality to a remarkable degree, 
and, even when all other nervous structures have disappeared, stains 
distinctly and is of normal shape. Secondary degenerations, of course, 
occur as soon as the axis-cylinders begin to swell, and are identical with 
those found in other complete transverse lesions. 

Acute Anterior Poliomyelitis. — In this disease, clinically desig- 
nated infantile palsy, the ganglion-cells of the anterior cornua of the 
spinal cord, their neuraxons passing out through the anterior roots, 
and the muscles over which they have trophic influence, are the princi- 
pal parts involved. The disease is undoubtedly due to hematogeneous 
intoxication or infection. It develops after exposure to cold, subse- 
quent to some other infectious disease, such as scarlet fever or measles, 
and occasionally has appeared as an epidemic. Children are almost 
exclusively affected, usually about the period of the second dentition, 
except in the epidemic form, when any age is liable to an attack. The 
nature of the poison that causes it is unknown. (See chapter on Filter- 
able Viruses.) 

Macroscopically the cord presents no characteristic external altera- 
tions. If section is made through the diseased portion, it can be seen 
that the tissues of the cord are somewhat redder than normal, particu- 
larly the anterior cornua of the gray matter, and minute hemorrhages 
may also be observed in this region. The tissue is somewhat softer 
than normal, and the blood-vessels are considerably distended. In 
old cases — that is, those with changes consecutive to the cessation of 
the acute process — the cord may be smaller and somewhat denser. 
Upon section it is readily observed that one or both of the anterior 
cornua are considerably reduced in size. The anterior roots from the 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 991 

diseased area may be considerably shrunken and fibrous. Microscopic- 
ally, in the early stages the most striking appearance is that presented 
by the blood-vessels. These are greatly distended and surrounded by a 
wall of round cells. The vessels in the gray matter of the anterior 
cornua, in the anterior commissure, and in the anterior septum appear 
to be chiefly involved. The posterior half of the cord presents few, if 
any, alterations. The neurogliar tissue seems to be somewhat looser, 
and throughout all the affected tissue there is more or less mononuclear 
cellular infiltration. The ganglion-cells are much altered. They may 
be swollen and colorless, the chromatin granules may be arranged in 
irregular masses, the processes are irregular, the nucleus may stain 
diffusely, and the nucleolus show vacuolar degeneration; the pericellular 
space is either distended by edema or by mononuclear cells. In all 
cases there seems to be a primary round-cell infiltration of the pia mater, 
which also penetrates the cord and follows the connective tissue. In the 
more advanced stages both nucleus and protoplasmic processes have 
disappeared, leaving nothing but the thickened axis-cylinder spring- 
ing from the cell. The perivascular spaces may be somewhat distended, 
and often contain round cells. Even in cases examined a few days after 
the onset it is evident that some of the ganglion-cells have degenerated 
completely and have disappeared, as their number is markedly dimin- 
ished. The fibers of the anterior roots show the ordinary forms of 
degeneration, the presence of globules of fat in the sheaths, and swelling 
or fragmentation of the axis-cylinders. The affected muscles very early 
exhibit fatty degeneration and atrophy of the fibers. In cases examined 
several months after onset considerable atrophy has usually taken place 
in the anterior horns. The perivascular round-cell infiltration is still 
very distinct, and usually compound granular cells are found in consider- 
able numbers in the lesions. The ganglion-cells are fewer, and those 
that remain may be either normal or partially degenerated. Many 
fibers have disappeared from the anterior roots, and the trophic changes 
in the muscles are still more pronounced. In those cases examined very 
late — that is, some years after the development of the process — the 
anterior horns appear to be markedly diminished in size, although this 
alteration is exceedingly unequal, often one horn being involved whilst 
the other is perfectly normal or exhibits only slight alterations. Occa- 
sionally the anterior horns appear paler, but of almost normal size, 
apparently the result of a colloid degeneration of the neuroglia tissues. 
The blood-vessels are dilated and their walls thickened, and they may 
contain some cellular infiltration. In those parts where the process is 
most severe all the ganglion-cells have disappeared; in others a few 
may remain, and these are usually normal. The neuroglia has under- 
gone hyperplasia, and consists of a coarse meshwork containing many 
nuclei. The medullated fibers of the anterior roots are partially or 
completely destroyed. Degeneration of the medullated fibers of the 
pyramidal tract may sometimes be traced for a few segments above the 
affected region; as a rule, it is slight, and involves only a few of the 
fibers. The lesions usually attack several segments of the cord, and are 
most frequent in the lumbar region, although any part may be affected, 
even the cells of the medulla. 



992 



A TEXT-BOOK OF PATHOLOGY 



The pathogenesis of the disease cannot be said to be settled, but it 
seems that virus arrives in the spinal cord by way of the anterior spinal 
artery and its accompanying lymph-channels. Within the cord it seems 
probable that spread occurs along the lymphatics. 

The clinical course of the disease is sufficient evidence of the fact 
that at least some of the cells recover their functions completely. After 
the paralysis has reached its greatest extent a very considerable degree 
of recovery may ensue, and only certain groups of muscles remain af- 
fected. Some of these degenerate and contract, giving rise to various 
deformities in the limbs. 

Landry's ascending paralysis is an acute spreading general muscular 
palsy due usually to an ascending myelitis, alone or combined with 
degenerative peripheral neuritis. The histological change in the cord 
may be that of poliomyelitis or a total ascending myelitis. The disease 
appears as a sequel to some of the acute infections, such as enteric fever, 
or without apparent antecedent cause; for such attacks many bacteria 
have been held responsible, but the cause is not yet settled. During 
an epidemic of poliomyelitis it is common to meet ascending and ful- 
minating cases of the Landry type. 

Inflammation of this class, that is, chiefly affecting the motor cells, 
may either ascend to or primarily involve the bulb or basal ganglia and 
cause superior poliomyelitis or polio-encephalitis. Pathologically the 
changes are the same, but there is relatively less tendency to gross 
degenerations. The lesions affect, of course, the ganglia of the cranial 
nerves. (See Bulbar Palsy.) 

Tuberculosis, aside from tuberculous meningomyelitis, is rare, but 
may occur as miliary tubercles or by coalescing of these into larger gran- 
ulomata. They cause transverse myelitis. Syphilis of the cord is said 
to appear as an acute degenerative myelitis in the secondary stage, and 
may occur as secondary to luetic meningitis. The most important 
results of syphilis are the fibrotic and degenerative lesions like tabes. 

PRIMARY DEGENERATIONS OF THE CORD 

Primary degeneration of the spinal cord is characterized by the more 
or less complete destruction of certain systems of fibers, affecting their 
whole length, without solution of continuity in any part of their course 
or distinct degenerative changes in the ganglion-cells from which they 
arise. Certain groups of fibers appear to be more frequently affected 
than others; these are particularly the columns concerned in the conduc- 
tion of impulses from or to the brain. They may be classified as follows : 
(1) The sensory neurons of the cord, which are composed of the unipolar 
cells of the spinal ganglia, and their neuraxons. They pass from the 
posterior roots into the spinal cord, and enter first the column of Burdach, 
subsequently bending into the column of Goll, and ending in the nuclei 
of Goll and Burdach in the medulla. (2) The central motor neurons, 
commencing in the pyramidal layer of the motor cortex, passing down 
through the internal capsule, the pyramids, and the pyramidal columns 
of the cord. (3) The peripheral motor neurons, commencing in the 
ganglion-cells of the anterior cornua, passing out from the anterior 
groups, and terminating in the muscles. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



993 



The most important primary degeneration is tabes dorsalis, or posterior 
sclerosis; it involves almost exclusively the sensory neuron. Involvement 
of the peripheral motor neuron gives rise to the disease known as pro- 
gressive spinal muscular atrophy; degeneration of both motor neurons, to 
amyotrophic lateral sclerosis. 

Posterior Sclerosis 

Degeneration of the posterior columns, when occurring independ- 
ently of distinct lesions of the posterior roots or section of the spinal 
cord — that is, as a definite form of disease — is known as tabes dorsalis, 
and corresponds clinically to locomotor ataxia. 

The fibers of the posterior roots appear to originate in the spinal ganglia. Upon 
entering the cord they divide into the ascending and descending branches, both of 
which give off collaterals. They may be divided into two groups, the lateral and the 
median bundles. The lateral fibers are somewhat finer and evidently belong embry- 
ologically to a different group, because they acquire their myelin-sheaths later and 
pass directly into the zone of Lissauer, thence into the substantia gelatinosa of 
Rolando, and some of them terminate in arborization about the cells of the columns 
of Clarke. The median bundles, which consist of coarser fibers, pass inward, then 
upward to the inner side of the posterior roots, then bend in and form the columns 
of Burdach, and, finally, those from the lower regions of the cord enter the columns 
of Gall and terminate in the nucleus and the medulla. Experimental degeneration 
caused by section of the posterior roots in animals, or destruction of the posterior 
roots as a result of pathological processes in human beings, causes ascending 
degeneration of the posterior column that corresponds very closely in many respects 
to the lesions of tabes dorsalis (Fig. 474). 




Etiology. — It now seems to be well established that syphilis occurs 
more frequently in the previous history of cases of tabes and of general 
paresis than in the previous history of other forms of nervous disease. 
According to various sets of statistics, it varies from 50 to 90 per cent, 
in all cases (Erb). The theory that syphilis is the important factor in 
the causation of tabes has received considerable support from the find- 
ings of Noguchi. This observer was able to detect the Spirochceta pallida 
in the cord of 12 out of 40 cases of tabes. The Wassermann reaction 
is positive in a large majority of instances. Nevertheless, a certain 
number of cases of tabes occur in persons who give no history of syph- 

63 



994 



A TEXT-BOOK OF PATHOLOGY 



ilis, have never had any symptoms of the disease, and present no signs 
of it at the time of examination. Reference is suggested to the discus- 
sion of paresis and syphilis of the nervous system where matter germane 
to this subject is also given. 

There has been considerable discussion as to whether this is due to 
systemic disease attacking primarily certain columns or tracts of fibers in 
the spinal cord, or to a condition secondary to disease of the posterior 
roots. 

Trepinski has combated the latter view, as a result of the comparison 
of the areas of degeneration in certain cases of locomotor ataxia with the 
areas of myelination in the cords of human fetuses. He believes that 
tabes is strictly a systemic disease, and Schaffer partially agrees with him. 
Obersteiner, however, after a careful review of their work, still adheres to 
the theory that the posterior roots are primarily affected. Edinger has sug- 
gested that those portions of the central nervous system that are sub- 
jected to excessive work are more likely than the others to feel the action 
of any toxin that may exist in the body — such, for example, as the toxin 
of syphilis. Siebert has slightly modified this theory, suggesting that 
at the point where the posterior roots enter the spinal cord they are 
most likely to be subjected to injurious overgrowth of the neuroglia 
that may be produced by the presence of toxins, exposure to cold, etc., 
while Marie believes that at this point a lymphangitis first makes its 
appearance. Hitzig believes that toxins may exist in the body for long 
periods of time, and so alter the blood as to cause it to produce, in the more 
susceptible portions of the nervous system, sclerotic changes. Ober- 
steiner has suggested that in all probability tabes is due to a variety of 
conditions, although he admits that syphilis is by far the most important. 

Pathological Anatomy. — The macroscopical lesions are as follows : 
The dura shows no changes; the pia mater in the segment between the 
posterior roots is somewhat thickened and opaque, a change which 
cannot usually be observed in the lateral and anterior regions. The 
posterior roots may be enlarged. In the advanced cases, however, they 
seem to be somewhat thinner and more translucent. On section through 
the cord the gray matter, especially that of the septum and anterior 
horns, appears to be normal. The anterior and lateral regions of the 
white matter are similarly intact. In the most advanced cases the white 
matter between the posterior roots is darker than normal and seems to be 
shrunken. Its consistency is somewhat softer than that of the normal 
cord, and the fact that it becomes depressed after section shows that there 
is some tendency to retraction. In early cases these changes may be 
slight; in fact, in cords removed from patients suffering from general 
paresis, in which the earliest stages are usually observed, there may be no 
macroscopical changes found. In these early stages sections stained by 
some myelin method exhibit the following changes : In the lumbar region 
the columns of Goll are degenerated, excepting the anterior portion; in the 
dorsal region there'are usually two areas of degeneration in the column of 
Burdach ; in the cervical region a portion of Goll's column is involved, and 
there are usually two areas on either side in the column of Burdach near 
the posterior horns. In nearly all cases there is usually more or less 
degeneration of the posterior roots. In the more advanced cases the 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



995 



portion of the posterior columns immediately behind the posterior com- 
missure contains normal fibers, but all the rest of the posterior column and 
Lissauer's zone are degenerated. In the cervical portion the degenera- 
tion of the column of Goll is most pronounced, and there is only a small 
number of normal fibers anteriorly and on either side lying close to the 
posterior roots. The degeneration extends upward through the medulla 
as far as the nuclei of Goll and Burdach. It occasionally happens that 
one portion of the cord seems to be more severely affected than the 
others; as a general rule, this is the lumbar region or the dorsal and 
lumbar regions, whilst the cervical portion shows fewer changes. Occa- 
sionally, however, the cervical portion of the cord will be particularly 
involved and the other regions more or less intact. In these cases the 
columns of Goll show only slight degeneration, whilst in the cervical 



Fig. 475. — Sclerotic and contracted posterior columns in posterior sclerosis (Karg and 

Schmorl) . 

portion the column of Burdach is markedly degenerated. As the fibers 
turn toward the center healthy fibers from the posterior roots of the 
cervical segments are usually less involved, so that the degenerated 
area lies near the posterior median septum, in the region usually called 
the middle root-zone. These degenerated areas are characterized by 
destruction of the myelin-sheaths and the axis-cylinders, their places 
being taken by proliferated neuroglia, which is characterized by the 
appearance of thicker and somewhat wavy fibers. In the late stages this 
hyperplastic neuroglia may undergo considerable contraction (Fig. 475). 
Proliferation of the neuroglia cells may be observed in the earlier 
stages, but in the later stages this has largely disappeared. The degen- 
eration of the fibers is in all respects similar to that of the ordinary 
secondary degeneration. Accumulation of the peculiar amyloid bodies 
is usually observed. The gray matter of the cord is little affected, the 
cells in particular rarely showing distinct traces of degeneration. The 
fibers that normally pass through the gray matter often disappear com- 




996 



A TEXT-BOOK OF PATHOLOGY 



pletely. This is true especially of the fine fibers of Lissauer's zone and 
those that form the plexus around the cells of the column of Clarke. 
The reflex collaterals also frequently disappear, and this is supposed to 
explain the loss of the reflexes, which is a common symptom of the dis- 
ease. The vessels usually exhibit some thickening of the adventitia 
and occasionally an accumulation of granular cells in the adventitia, or 
beneath the ependyma. Hyaline degeneration is found occasionally. 
The pia mater, corresponding to its macroscopical appearance, shows 
some thickening of the fibers, although this is absent in the earlier cases. 

The most interesting subject connected with this disease is the con- 
dition of the peripheral nerves, the spinal ganglia, and the posterior 
roots. Degeneration of the peripheral cutaneous nerves is frequently 
observed, the changes consisting of thickening of the perineurium and 
the connective-tissue trabecule, more or less degeneration of the myelin- 
sheaths, and occasionally swelling of the axis-cylinders. 

The results of the examination of the spinal ganglia have been 
very contradictory, and some authors find them intact, while others 
describe contraction and irregularity in the outlines of the cells. In no 
case, however, have the changes been sufficiently pronounced to account 
for the extensive degeneration in the posterior columns. The posterior 
roots are invariably degenerated. Some of the fibers are completely 
destroyed, others show disappearance of the myelin-sheaths and altera- 
tion of the axis-cylinders. Nageotte claims to have discovered a round- 
cell infiltration in the membranes surrounding the roots that causes 
a pressure degeneration. Redlich and Obersteiner believe that the 
changes are most marked after the entrance of the fibers into the cord, 
and explain this by supposing that there has been a slight constriction 
at the point where they pierce the pia mater. At times the basal ganglia 
and the cranial nerve centers are involved in a degeneration compar- 
able with that in the root ganglia and in such instances peripheral 
cranial nerve damage also exists. This seems to affect especially the 
oculomotive, pharyngeal and pneumogastric centers. 

Friedreich's Ataxia . 

Friedreich's ataxia is a disease characterized by inco-ordination of 
the gait, the first symptoms coming on usually during puberty. It 
belongs to the hereditary type of diseases, occurs in successive genera- 
tions of the same family, and appears to have no other causation. The 
most constant change is hypoplasia of the spinal cord. This hypoplasia 
may be regular, so that the whole cord is three-fourths or even less of 
its normal diameter, or it may seem irregular in the latter instance 
being, perhaps, more pronounced in the cervical and upper dorsal 
regions. Hypoplasia of the cerebellum is a frequent associated lesion. 
The two conditions are, however, rarely equal, and, according as one or 
the other preponderated, Marie described spinal and cerebellar forms 
of hereditary ataxia. The next most common lesion is degeneration 
in the posterior columns. This is particularly marked in the column 
of Goll, but, in severe cases, may also involve the column of Burdach. 
No degeneration at all may be found, such a case has been reported by 
Nonne, but in these instances the larger fibers are usually absent. 



DISEASES OF THE SPINAL COED AND ITS MEMBRANES 997 

Degeneration in Clarke's columns is not uncommon. In regard to the 
degenerative areas found in the lateral columns there is much difference 
of opinion. The majority of authors believe that they represent de- 
generation of the pyramidal columns, although it is certain that none 
of the clinical symptoms associated with this lesion are present. The 
degeneration is usually most pronounced in the lower part of the cord, 
diminishes in intensity upward, and disappears near the normal decus- 
sation of the pyramidal columns. According to Marie, the degener- 
ated areas usually lie to the outer side of the normal situation of the 
pyramidal columns. In all these degenerated areas there is consider- 
able proliferation of the neuroglia tissue, the fibers being especially 
increased, indicating the likelihood that the change is secondary. 
Other secondary changes are the thickening and partial adhesion of the 
pia mater, particularly that part in contact with the posterior columns 
of the spinal cord, and also the thickening of the walls of the blood- 
vessels, such as is usually found in sclerotic nervous tissue. Degenera- 
tion is also found in the posterior roots, which are smaller than normal. 
In regard to the condition of the peripheral nerves there is some differ- 
ence of opinion, but it seems certain that, in some cases at least, there 
is a degeneration of the sensory fibers. The disease partakes, therefore, 
of the nature of a combined sclerosis. Some authors hold that it is 
due primarily to a hypoplasia of the third primary vesicle and of the 
neural canal — that is to say, the medulla, cerebellum, and cord. The 
disease, however, appears to be slowly progressive, and it is not evident 
in infancy. This may be explained by assuming that the hypoplastic 
central nervous system is sufficient for the needs of the child, and that 
as the organism develops it becomes relatively insufficient. This, how- 
ever, would not enable us to understand why such extensive secondary 
degenerations are sometimes present. 

Amyotrophic Lateral Sclerosis 

Amyotrophic lateral sclerosis is a disease which, theoretically, should 
present the following pathological changes: Degeneration in the pyra- 
midal columns, atrophy of the ganglion-cells of the anterior cornua, 
degeneration of the nerve-fibers in the anterior roots and of the motor 
fibers in the peripheral nerves, and degenerative atrophy of the muscles. 
The lesions that are actually found, however, are very various. Common 
to almost all cases is the atrophy of the motor cells of the spinal cord and 
degeneration of their neuraxons, and the presence of compound granular 
cells, but there is no other sign of inflammatory reaction. The degen- 
eration of the ganglion-cells is usually extensive, and the muscles exhibit 
the changes characteristic of progressive spinal muscular atrophy — ■ 
that is, swelling of the fibers, increase of the number of the nuclei, 
indistinctness of the striation, and increase in the amount of connective 
tissue, with, in the later stages, extreme atrophy of the fibers. The 
degree to which the pyramidal columns are affected is not constant; at 
times the degeneration is pronounced and extends as far as the internal 
capsule. Indeed, distinct alterations have been reported in the motor 
cortex of the brain — that is to say, degeneration of the ganglion-cells 
and the presence, in more or less considerable number, of compound 



998 



A TEXT-BOOK OF PATHOLOGY 



granular cells. In other cases the degeneration may cease at a lower 
point, and in at least one case was not found at all. It has been sup- 
posed that in such cases there is only a slight alteration in the nutrition 
of the ganglion-cells, and that the degenerative changes commence at 
the peripheral portion of the neuraxon and advance cellipetally. The 
changes found in the pyramidal columns are, of course, similar to those 
occurring in the other primary degenerations. 




Fig. 476. — Multiple sclerosis. Second cervical cord. The spinal roots stain well and are 

not affected by the disease. 



Fig. 477. — Optic nerve, showing degeneration in central parts. Photographs from the 

case illustrated in Fig. 478.) 

Chronic anterior poliomyelitis, or progressive spinal muscular 
atrophy, is strictly a degeneration of the peripheral motor neuron, and 
while it at times seems to be inherited or familial, it is probably only a 
part of a general neuropathic tendency, for syphilis so often occurs in 
the history that it assumes an important etiological role. It is character- 
ized by gradual atrophy of the ganglion-cells of the anterior cornua and by 
diminution of the size of the cornua themselves. No lesions that dis- 
tinctly indicate the existence of an inflammatory process are present. 
The cells gradually grow smaller, become pigmented, and may ultimately 
disappear. There is degeneration of the fibers in the anterior roots and 
degenerative atrophy of the muscles. The clinical course is slowly but 
irregularly progressive. The condition in many respects resembles 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



999 





Fig. 478. — Transverse sections of the medulla and cord from a case of multiple sclerosis. 
Stained" by Weigert's method. (Normal tissue colored dark, degenerated areas white.) 
1. Medulla. 2. Lower medulla. 3. Third cervical. 4. Fifth cervical. 5. Second dorsal. 
6. Sixth dorsal. 7. Twelfth dorsal. 8. First lumbar. The irregular areas of degeneration 
in different segments of the cord are not associated with secondary degeneration below or 
above the different lesions, except the degeneration in the posterior columns from the 
second dorsal up to the medulla (Burr and McCarthy). 



1000 



A TEXT-BOOK OF PATHOLOGY 



amyotrophic lateral sclerosis, and cases have been recorded in which 
other degenerations were found, particularly in Clarke's column and in 
the posterior columns. The lesions apparently commence in the cervical 
region, and may later extend to other parts of the cord, and even to the 
motor nuclei of the medulla. This last causes so-called bulbar, or glossio- 
labiolaryngeal palsy, which follows the clinical and pathological char- 
acters of the rest of these affections with limitation of the lesions to the 
medulla, with perhaps an added degeneration of the pyramidal tracts. 
There is a form of chronic poliomyelitis in which distinct lesions of the 
vessels are present, and which is apparently only a slow form of the 
ordinary acute poliomyelitis. 

Combined sclerosis, giving rise to ataxic paraplegia, has been de- 
scribed in a great number of instances, and a characteristic symptom- 
atology has been ascribed to the condition. Usually the parts affected 
are the posterior columns and the lateral areas including the pyramidal 
and direct cerebellar tracts, but the posterior root area is not greatly 
involved; the gray matter is not often markedly degenerated. The 
lesions do not vary greatly in appearance from those of the other forms 
of primary degeneration, only differing from tabes in the pronounced 
vascular changes, large prominent axones and overgrowth of spider 
cells. The areas are gray, somewhat shrunken, and contain an ex- 
cess of neuroglia, granular cells, and amyloid bodies. The nature of the 
process is still undecided. The frequency with which a certain definite 
combination occurs has led some neuropathologists to believe that it is 
a morbid entity. Others, however, contend that the parts of the cord 
affected are those least able, on account of their poor blood-supply, to 
resist noxious influences, and that, therefore, the disease is only the 
reaction of the weaker parts of the spinal cord to a general morbific 
agent. The disseminated or multiple scleroses are commonly associated 
with similar lesions in the brain, and haye been described under that 
heading (p. 964). 

Lateral sclerosis, with exclusive involvement of the lateral columns 
connected with the motor cortex or upper neuron, is very rare in a pure 
form. There is retained muscle tone because the trophic cells in the 
gray matter of the cord are not attacked. At first there is spasticity 
and, later, paralysis of the affected muscles. 

Degenerations in the white matter of the spinal cord have 
been described in various forms of chronic anemia, especially pernicious 
anemia. Two varieties can be distinguished, those in which the areas 
of sclerosis are disseminated irregularly through the cord, and those 
in which the degeneration is systemic in nature and follows more or 
less closely the area of distribution of the fibers of the posterior root. 
In the latter case the posterior columns are affected most severely, and 
the lesions are most pronounced in the cervical region. Degeneration, 
however, may also be found in the lateral columns, either involving 
only a small patch of fibers, or so extensive as to give rise to the appear- 
ance of combined sclerosis. The degeneration appears to occur prima- 
rily in the nerve-fibers, with secondary proliferation of the neuroglia. 
Vascular changes, particularly minute hemorrhages and thickening of 
the vessel walls, are also found, and when present the nerve-fibers in the 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 



1001 



immediate vicinity of the vessels are often degenerated. These changes 
are not, however, found in all cases of progressive pernicious anemia, a 
number of cases being now on record in which the spinal cord showed 
no trace of degeneration. No satisfactory explanation has hitherto 
been given to account for them. It has been suggested that the anemias 
with spinal lesions belong to a different group, but this is, of course, a 




1 2 3 

Fig. 479. — Sections from a case of ataxic paraplegia, showing system degeneration of 
the posterior column, lateral (crossed), pyramidal, and direct cerebellar tract: l.'Cervical; 
2, lumbar; 3, sacral (Burr and McCarthy). 




3 

Fig. 480. — Descending degeneration of direct and crossed pyramidal tracts following 
hemorrhage into the medulla: 1, Dorsal region; 2, lumbar region; 3, cervical region (Mc- 
Carthy and Pearce) . 

\k The lesions presented in the above sections are confined to the motor system, and 
caused a spastic type of paralysis without sensory derangement. 

mere hypothesis. The absence of degeneration in the posterior roots 
seems to exclude a peripheral neuritis, although it is possible that in 
case of slight disease of a spinal ganglion the terminations of its nerve- 
fibers in the medulla would exhibit the first trace of degeneration, and 
this, in fact, corresponds with the condition found in some of the cases. 
Similar changes have also been found in other conditions, especially 



1002 



A TEXT-BOOK OF PATHOLOGY 





3. Diffuse degeneration of cord in intense anemia associated with chronic parenchymatous 

nephritis (cervical cord). 

Fig. 481. — 1, 2, and 3 present the diffuse toxic lesions met with in anemic and cachectic 
conditions. The degeneration is diffuse, not confined to any particular tract of the cord, 
but usually predominating in the posterolateral areas. It is not infrequently referred to 
as posterolateral sclerosis. No. 1 is from an early case, and shows the relation of the 
degeneration to the arterial supply of the posterior columns. 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 1003 

the chronic cachexias, such as tuberculosis, diabetes, and carcinoma. 
Changes occurring in the spinal cord in ergotism and pellagra have been 
described. In the former the areas of degeneration are said to be chiefly 
in the posterior columns, limited, excepting in the cervical regions, to 
Burdach's column, and there are lesions in the posterior roots. In 
pellagra degeneration is found in Goll's column, particularly in Bur- 
dach's column, and usually in the lateral columns also. There are 
also partial disappearance of the cells of the anterior cornua and small 
degenerative foci in the anterior columns. Changes limited to the poste- 
rior column have also been noted after diphtheria and leprosy. In old 
age small, irregular areas of degeneration, particularly in the posterior 
median column, and sometimes at the periphery of the spinal cord, may 
be observed. 




Fig. 482. — Sclerosis of the white substance of the cord. 



SECONDARY DEGENERATIONS OF THE CORD 

Secondary degenerations of the spinal cord occur after any lesion 
interrupting the course of one or more of the columns of fibers, and also 
after any disease of the ganglion-cells that nourish these fibers. They 
have been divided into ascending and descending, according to the 
direction in which the degeneration proceeds. It will be clear from the 
description already given of the course of the columns of the cord that 
the chief variety of descending degeneration will be that of the pyra- 
midal columns. This may occur as a result of injury to the motor cortex, 
or of interruption of the motor fibers in any part of their course from 
the cortex to the conus terminalis. If the lesion is unilateral and above 
the decussation, ordinarily only one pyramidal column is distinctly 
affected — that is to say, the anterior pyramidal tract of the same side 
and the lateral pyramidal tract of the opposite side. Careful micro- 



1004 



A TEXT-BOOK OF PATHOLOGY 



scopical investigations, however, have shown that certain fibers that do 
not decussate pass down the spinal cord in the lateral columns. In 
cases of long-standing secondary degeneration of the pyramidal columns 



4 9® 




Fig. 483. — Acute gliomatous degeneration of the spinal cord, showing relative size of cord 

in different localities. 

a certain amount of simple atrophy of the ganglion-cells of the anterior 
cornua has been observed. Descending degeneration has also been 
observed in the posterior columns. In the upper portion of the cord 




Fig. 484. — Highly magnified section of the cord from the same case. The white areas 
correspond to an active proliferation of the neuroglia cells with destruction of the myelin- 
sheaths. There was no secondary degeneration below the cervical cord. The disease ran 
an acute course and presented an ascending type of paralysis (McCarthy and Pearce). 

it assumes the form of two small areas that project from a point slightly 
posterior to the gray commissure and extend backward and outward. 
This has been called the comma degeneration of Schultze. In the lower 
part of the cord these descending fibers appear to approach the posterior 



DISEASES OF THE SPINAL CORD AND ITS MEMBRANES 1005 

commissure and form the oval field of Flechsig. Descending degenera- 
tion for a short distance below a total transverse lesion may be found 
in all the columns. Ascending degeneration occurs chiefly in the poste- 
rior columns, and is described in connection with tabes dorsalis. In 
case of isolated injury to one of the posterior roots, there may be traced 
upward a slender band of degeneration that gradually approaches the 
posterior septum. Ascending degeneration also occurs in the direct 
cerebellar tract, and may often be found to be associated with disease 
of the ganglion-cells in Clarke's columns. It extends as far as the 
restiform bodies in the medulla. Ascending degeneration also occurs 
in the anterolateral tract of Gowers. After total transverse lesion 
secondary alterations may usually be detected in the remote portions 
of the cord in the course of from five to seven days. These alterations 
consist of a swelling of the axis-cylinders and, within a very short time, 
fatty degeneration of the myelin-sheaths. Granular cells appear early 
in the tissue. In the course of a month the degenerative changes are 
quite pronounced, and may readily be detected by Weigert's method. 
The myelin-sheaths have disappeared wholly or in part; the axis cylinders 
have also vanished, although some varicose fibers may be found here 
and there in the lesion. Compound granular cells largely fill the field, 
but there is also a distinct hyperplasia of the neuroglia tissue, giving 
the area, macroscopically, a somewhat grayish appearance. Still later, 
contraction begins to occur and the appearances seen in the primary 
degenerations are found. 

TUMORS 

Glioma. — Of the primary tumors of the spinal cord, the most fre- 
quent and important is glioma. This is usually infiltrating in type 
and elongated, extending for a distance of several segments along the 
cord, and sometimes involving the nerve-roots, causing them to swell 
and become harder. It may give rise to curious distortions in shape, 
and an apparent hypertrophy; this latter is probably the result of the 
compression in a longitudinal direction of some portion of the cord, 
so that in a given section more ganglion-cells are found than would 
normally be present. 

Proliferation of the neurogliar tissue of the cord, causing increase 
in size of the segments affected' — often without, however, distinctly 
injuring the normal tissue of the cord — may be produced by pressure 
on the outside or by interference with the circulation. It occurs in 
cases of tumor of the membranes or of the spinal column, in disease of 
the spinal column, and in pachymeningitis. The neuroglia tissue fre- 
quently contains, in addition to the increase in the number of fibers, 
huge multipolar cells that have been described in true gliomata by 
Stroebe. 

Sarcoma alone, or containing gliomatous or mucoid tissue, or of 
the type known as angiosarcoma, may also appear. 

Carcinoma and sarcoma may also appear as metastatic growths. 

Cysts are exceedingly rare, but both the echinococcus and the 
Cysticercus cellulosce have been reported. 



CHAPTER XIV 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 

The Ganglia of the Cranial and Spinal Nerves 

The ganglia of the spinal nerves may be diseased as a result 
of extension of pathological processes, usually tuberculosis, from the 
surrounding bony structures. It is probable that they are also subject 
to inflammatory changes. Spiller and Keen have reported the results 
of the examination of a number of Gasserian ganglia removed on ac- 
count of persistent trifacial neuralgia, in which they found degeneration 
— in some cases total — of the myelin-sheaths and the nerve-fibers in the 
ganglia. In one case the degenerated nerve tissue was replaced by 
connective tissue, giving rise to marked sclerosis. Occasionally the 
cells in the ganglia had undergone atrophy, and in all instances the 
vessels were distinctly sclerotic, the lumen being sometimes completely 
obliterated. The authors believe that these changes are not primary, 
but secondary to lesions in the peripheral sensory nerves. 

The spinal ganglia may also be diseased. Slight degenerative 
changes have been noted in locomotor ataxia and as a result of periph- 
eral neuritis. In this case the walls of the ganglia show swelling and 
granulation of the chromatin bodies, and are often somewhat shrunken. 
More frequently the ganglia are involved as a result of disease of the 
surrounding bones; particularly caries or sarcoma of the spine may 
produce pressure, resulting in atrophy, or, in the case of the former, 
areas of tuberculous softening. The ganglia of the spinal nerves are 
sometimes found diseased in cases of herpes zoster, there being hemorrhage 
into the sheath, on which membrane there may be round cell infiltration. 
This may go on to hyperplasia apparently of nerve elements, glia-like 
cells and connective tissue. Degeneration of the nerve fibers connected 
with such ganglia is the rule. Tetanus and hydrophobia practically 
always produce chromatolytic degeneration of the essential ganglion 
cells, to which may be added round cell infiltration or even hemorrhage. 

The Nerves 
circulatory disturbances 

Hyperemia of the nerve-trunks attends acute inflammations. The 
vessels of the perineurium may be intensely injected. 

Hemorrhages may result from acute congestion or from traumatic 
injuries. They take the form of punctate ecchymoses in the perineurium 
or endoneurium. 

Edema of the nerve-trunks may occur in the nerves traversing areas 
of inflammation. 

1006 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 1007 

ATROPHY AND DEGENERATION 

Atrophy of the nerves occurs in consequence of pressure upon the 
nerve or as a result of disease (neuritis) of the nerves. It may also 
result from disease of the central nervous system, causing disturbance 
or destruction of the nuclei of origin of the peripheral nerves. Occa- 
sionally atrophy arises without definite cause in old age. The changes 
in the nerve are similar to those following section of the nerve, and are 
described under the heading Degeneration. 

Degeneration. — Injury of a nerve in its course produces various 
manifestations in the nerve-fibers corresponding more or less to the 
nature of the destructive agencies. It is obvious that if the nerve be 
divided by a clean incision, the degenerative changes below the point 
of incision will be less extensive than if the destructive agent is severe, 
such as in cauterization, the crushing of the nerve-trunk with extensive 
disintegration, or the removal of a section of some length. Still milder 
changes, however, may be produced by a ligature that is not drawn 
tightly enough to destroy completely all the nerve-fibers. Degenerative 
changes are less pronounced if there is prompt coaptation of the injured 
ends, or if the continuity of the nerve is not entirely destroyed. 

If a nerve is examined immediately after injury, there will be found 
only deformity of the nerve-fibers. This consists in dislocation of the 
myelin and perhaps fibrillation of the axis-cylinder, so that it seems 
to be crushed into and diffused throughout the white substance of the 
nerve-fiber. Within a few hours the cells in the myelin-sheath begin to 
exhibit signs of degeneration, the chromatin swells, stains more feebly, 
and may undergo fragmentation. At the end of eighteen hours the axis- 
cylinder is usually slightly swollen and its outline becomes irregular. 
These changes, however, are by no means uniform throughout the whole 
nerve, some parts perhaps being almost normal and others extensively 
degenerated. At the end of thirty-six hours the myelin substance has 
undergone fatty degeneration, with the formation of small globules. 
These changes are found on both sides of the lesion, on the proximal 
side extending to the first node of Ranvier, and on the peripheral side 
extending considerably beyond this. At first the changes in both frag- 
ments are approximately equal, but those in the peripheral end rapidly 
progress and soon dominate the field. The changes in the peripheral 
fragment, however, are more pronounced near the lesion and diminish 
toward the periphery. In the central end there are nearly always a few 
fibers that degenerate as far as the spinal cord, but these are the excep- 
tion. 

REGENERATION AFTER INJURY OF A NERVE 

The first sign of regeneration is proliferation of the cells of the sheaths. 
Their nuclei exhibit karyokinetic figures, and there appears to be an 
increase in their protoplasmic substance. At the same time the cells of 
the connective tissue also undergo multiplication and, to a certain 
extent, act as phagocytes, absorbing the fatty detritus. The protoplasm 
of the cells of the sheath gradually elongates and occupies the situation 
of the myelin substance and the old axis-cylinder. There appears 
to be some doubt whether these changes are more pronounced in the 



1008 



A TEXT-BOOK OF PATHOLOGY 



proximal or distal fragments; at any rate, the protoplasm of the cells 
of the sheaths on both sides of the lesion seem to possess phagocytic 
properties and to absorb some of the fat and detritus resulting from the 
degenerative changes. The protoplasmic mass usually closes the free 
ends of the nerve-fibers, and assumes a somewhat conical form, not 
unlike a node of Ranvier. This mass appears to be continuous with the 
partially degenerated end of the axis-cylinder. Toward the end of the 
first week the elongated protoplasmic masses in the end of the nerve- 
fibers become somewhat differentiated. In the interior may be seen a 
delicate fibrillated structure that appears to be continuous with the 
axis-cylinder of the nerve; outside of this is a delicate membrane, but 
both of these structures lie within .the old myelin-sheath, in as far as 
it is preserved. It is probable that mildly damaged axis-cylinders, or 
those with a moderate grade of chromatolysis, can regenerate, but when 
the injury is severe or the nerve-fiber completely severed and separated 
it is not likely that union of the segments results. Both the proximal 
and peripheral fragments of the axis-cylinder degenerate and a new one 
must grow from the cell. Axis-cylinder regeneration must, of course, 
be preceded or accompanied by processes in the sheath and neurilemma. 
As the new nerve-fibers increase in length they gradually pass through 
the injured area and come in contact with the proximal area of the 
peripheral fragment. In this the cells of the sheath have undergone 
proliferation and have formed protoplasmic masses at the ends of the 
fiber. Differentiation in this protoplasmic mass does not, however, 
appear to occur until the new axis-cylinder reaches it. Gradually the 
nerve approximates more and more closely to the normal appearance, 
the axis-cylinder becoming more distinct and the myelin-sheath thicker 
until it can be said to be re-established. In the course of the absorption 
of the fatty and other detritus, cells that are filled with fat-droplets 
accumulate in the connective tissue of the nerve and between the fibers, 
which are probably ordinary compound granular cells. It is question- 
able, however, whether they are derived from the endothelium of the 
lymph-spaces or from the leukocytes, or whether they represent the 
excess of the proliferated cells of the sheath. Somewhat later, con- 
centric masses may be found that resemble very closely the amyloid 
or hyaloid bodies of the central nervous system. 

INFLAMMATIONS 

Neuritis may be either acute or chronic. It has also been classified 
as parenchymatous and interstitial; the former comprising the degenera- 
tions of the nerve-fibers without involvement of the connective tissue, 
and the latter comprising all those forms associated with the character- 
istic signs of an inflammatory process in the connective tissue of the 
nerve. 

Acute interstitial inflammation, or neuritis proper, may be caused 
by direct extension from an inflammatory focus in the surrounding 
tissue or by trauma, or as the result of some as yet unknown poison 
which is generally supposed to be infective in nature. It may also 
occur in the course of acute infectious diseases, or as an independent 
condition, as in beri-beri. The inflammatory changes occur in the 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 



1009 



perineurium and the endoneurium. The nerve is swollen, soft, and 
pinkish in color. Microscopically, both the perineurium and the 
trabecule of connective tissue are increased in size, the blood-vessels are 
distended, and there is extensive round-cell infiltration. In the acute 




Fig. 485. — Neuritis: longitudinal section, showing degenerated nerve-fibers (black); 

Azoulay's method; X 300. 

forms partially degenerated fibers with fatty myelin-sheaths and swollen 
axis-cylinders are found very early. The primary change unques- 
tionably occurs in the connective tissue, and the nerve-fibers are in- 
volved secondarily, the myelin-sheaths being the parts first affected. 




Fig. 486. — Chronic hypertrophic interstitial neuritis; X 100 (case of Dejerine). 

Chronic interstitial neuritis may follow the acute form or com- 
mence as an independent condition. The nerve is harder than normal, 
the connective tissue is increased, the walls of the blood-vessels are 
thickened and their lumina may be partially obliterated. More or 
less round-cell infiltration is found in the hyperplastic connective tissue, 
and the nerve-fibers show extensive degeneration, many of them having 
disappeared, and the few that remain presenting marked morbid changes. 

64 



1010 



A TEXT-BOOK OF PATHOLOGY 



Often there is a distinct proliferation of the cells in the neurilemma. 
This form of neuritis in particular is associated with muscular degenera- 
tion, and appears to give rise to the type known as the neural form of 
progressive muscular atrophy. Associated changes are often found in 
the spinal cord, and consist of an ascending degeneration on the posterior 
columns and more or less alteration of the ganglion-cells. In a variety 
of this disease, described by Dejerine under the name of chronic hyper- 
trophic interstitial neuritis, there is an actual overgrowth of the con- 
nective tissue, the nerve-trunks forming huge, firm cords, several times 
the normal thickness, that may readily be felt beneath the skin. This 
disease is apparently due to some hereditary familial influence. Micro- 
scopically, the changes consist of an enormous proliferation of the 
connective tissue with round-cell infiltration, partly about the sclerotic 
blood-vessels, and pronounced degeneration of the nerve-fibers. The 
muscles undergo degenerative atrophy, and there are secondary degen- 
erations in the spinal cord. 

Suppurative neuritis is nearly always secondary to suppuration in 
the tissue surrounding the nerve. It is characterized by the presence 
of small foci of pus in the connective tissue and softening of the nerve- 
trunk. The nerve-fibers degenerate very rapidly. 

Parenchymatous neuritis is characterized by a primary degenera- 
tion of the nerve-fibers, the alterations in the connective tissue being 
secondary. It is always due to some toxic or infectious substance cir- 
culating in the fluids of the body. The most common causes are lead, 
arsenic, alcohol, and diphtheria; but it also occurs as a result of other 
poisons and infectious diseases, and in the course of tabes dorsalis. The 
nerve-trunk becomes slighter, firmer, and grayer. Inflammatory changes 
are slight or absent, while the degeneration of the nerve-fibers is pro- 
nounced. Changes have frequently been found in the cells in the ante- 
rior cornua of the spinal cord. 

Polyneuritis does not differ from the isolated form, excepting that a 
number of nerve-trunks in various parts of the body, usually the limbs, 
are affected at the same time. It is most frequently of the parenchy- 
matous type. 

INFECTIOUS DISEASES 

Tuberculosis of the nerve-trunks is due to direct extension. It 
most commonly affects the roots of the nerves, and occurs in the course 
of tuberculous spinal or cerebral pachymeningitis. The connective tissue 
is first affected, and may contain small cheesy foci, in which epithelioid 
and giant cells are found. The nerve-fibers degenerate secondarily. 

Syphilis also occurs, chiefly in the nerve-roots. It causes over- 
growth of the connective tissue, particularly in the perineurium, with 
pressure upon and degeneration of the nerve-fibers. Gummata are 
sometimes observed upon the cranial nerves. 

Leprosy is characterized by the presence, in the connective tissue 
of the nerve-fibers, of large epithelioid cells containing vacuoles more or 
less filled with lepra bacilli. The bacilli cause a certain amount of 
hyperplasia of the connective tissue, which presses upon and eventually 
destroys the nerve-fibers. The disease affects the small cutaneous 



DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 



1011 



nerves almost exclusively, and causes anesthesia and trophic changes 
in the skin. 

TUMORS 

Neuroma. — The tumors embraced by this term have been suffi- 
ciently described under the heading Neuroma, in Part I. 

Sarcoma is a rare tumor of nerve-trunks. It takes its origin from 
the connective tissues of the nerve. 

Muscle=fibers are sometimes found in intramuscular nerve-trunks. 
They usually exhibit proliferation of the nuclei, but the striations remain 
distinct. Their position has been ascribed to errors of development, 
but it is not certain that they are without function. 



CHAPTER XV 



THE EYE 

ANATOMY 

The Conjunctiva. — -This is a sac lined with stratified epithelium 
covering the exposed portion of the eyeball and reflected to the lids, at 
the margin of which it becomes continuous with the skin. When this 
sac is dissected off and spread out it is as large as the palm of the hand. 
Upon the inner surface of the lids and upon the ball there is squamous, 
near the canthus, columnar epithelium. In the latter situation goblet- 
cells abound. Beneath the epithelium is a loose areolar and adenoid 
layer and then a thick connective-tissue layer, the so-called tarsal car- 
tilage which contains the Meibomian glands. The subepithelial layer 
upon both lids and ball is loose but highly vascular. 

The lachrymal apparatus consists of a compound racemose gland 
lying in the upper outer portion of the orbit, discharging tears through 
two ducts into the lachrymal sac at the internal canthus, by the lachry- 
mal puncta near the caruncle. The tears are expressed from this sac by 
the contraction of the palpebral sphincter and forced into the nasal 
duct. They are spread over the conjunctival surface by nictitation. 

The cornea is a transparent avascular epithelial structure continuous 
at its margin with the sclera. From without inward there is first a 
squamous epithelial layer continuous with the epithelium of the con- 
junctiva, covering the acellular outer capsule, or Bowman's membrane. 
The body of the cornea is composed of lamellated epithelium com- 
parable to the horny epidermis, between the layers of which course 
lymph-channels; the interstitial branched cornea cells lie in lacunae. A 
hyaline internal capsule (Descemet's membrane), lined on the surface 
of the anterior chamber by a single layer of endothelium, constitutes 
the innermost part of the cornea. The cornea is without blood-vessels, 
nutrition being derived from vascular plexuses at its juncture with the 
sclera. The two internal layers join with the structures of the uveal 
tract. 

The sclera is the stiff external capsule of the eyeball, composed of 
variously arranged bundles of white connective tissue with some yellow 
elastic fibers. 

The lens is a transparent convex epithelial body lying immediately 
behind the iris, surrounded by an acellular capsule thickest anteriorly. 
The body is formed of homogeneous fibers which grow from the capsule 
of the equator and the portions just anterior to this zone, the origin 
of these fibers being a layer of transparent polygonal cells lying below 
the lens capsule. The older fibers are pressed toward the center to 
form a nucleus. The lens is held in position by fibers from the ciliary 
body. 

1012 



THE EYE 



1013 



The vitreous humor is a soft, gelatinous, clear, colorless tissue occupy- 
ing the center of the inner eye. It contains a few leukocytes j and 
branching cells, the processes of the latter being attached to the delicate 
vitreous capsule to form a supporting framework. 

The iris, ciliary body, and choroid form the uveal tract. The first 
consists of an anterior and posterior layer of endothelium beneath which 
is a hyaline layer and a central muscle. The endothelium in front is 
continuous with Descemet's membrane, that posteriorly extends into the 
choroid over the ciliary processes. The central layer contains radiate and 
annular muscle-fibers which find their origin and support in the ciliary 
body. This latter structure is a fibromuscular area containing cavernous 
lymph-spaces for the entrance and exit of the aqueous humor which is 
produced by the ciliary processes. The aqueous humor, a fluid occupying 
the spaces in front of the lens, is a modified lymph without leukocytic 
content, containing a very low percentage of protein and sugar. The 
last is in greater amount than in the blood-serum, and varies directly 
as this latter, except in diabetes, when the sugar content is relatively 
very high. The choroid is the posterior extension of the ciliary body and 
extends to the opening for the optic nerve. The anterior part is supplied 
with blood by the ciliary branches of the vessels supplying the ocular 
muscles, the posterior part by the vessels in the optic nerve, and these 
two sets anastomose. 

The Retina. — This layer of the eye is the specialized "end-organ of 
the optic nerve. It spreads from the nerve-head to the ciliary body. 
It consists from the choroid inward of a pigmented layer upon which 
lies the neuro-epithelial layer of rods, cones, and fibers, which latter is 
separated from the nuclear, ganglion, and nerve-fiber layer by a dense 
neurofibrillar layer. The retina is limited internally by a condensation 
of nerve-fibers arising in the deeper layers. This membrane is supplied 
with blood by a vessel entering with the optic nerve, which is the sole 
avenue for circulation; it gives off terminal branches that do not 
anastomose with arterioles in other coats. 

The eye lies in the anterior part of the orbit supported by fat and 
muscles. 

CONGENITAL ABNORMALITIES 

Anophthalmia is complete absence of the eye, a rare condition; while 
microphthalmia, abnormal smallness of one or both eyes, is more com- 
mon. Abnormalities due to formations in defectu comprise: synoph- 
thalmia, or cyclopia, a condition in which the prosencephalon fails to 
divide correctly, a single orbit and eye resulting; cryptophthalmia, in 
which the bulb is hidden by failure of the lids to divide. The lids show 
as the most frequent abnormalities: coloboma, an angular defect with 
its base on the free margin; congenital ptosis, and epicanthus, a fold of 
skin passing across the inner canthus from the upper to the lower lid. 

CONJUNCTIVA 

Circulatory Disturbances. — Anemia of the conjunctiva aloneYis 
an unusual condition, but pallor is common in general anemia. 

Hyperemia is common, and has as its chief cause external mechanical 



1014 



A TEXT-BOOK OF PATHOLOGY 



irritation, foreign, bodies, or gases. It may be a sign of errors of refrac- 
tion, depending upon physical changes in the eye. It is present as an 
early stage of inflammation. 

Hemorrhage beneath the membrane may occur from traumatism, 
or by undue muscular effort in the presence of diseased vessel walls. 

Edema occurs as part of general edema, in inflammation of deeper 
ocular tissues, in certain oculomotor paralyses, as a result of local venous 
obstruction, and in infections of neighboring sinuses. 

Degenerations of the conjunctiva are rare, but homogeneous 
metamorphoses have occurred in edematous hyperplastic lesions of the 
epithelial, areolar, and adenoid layers, to which the names colloid and 
hyaline or even amyloid degeneration have been given. 

Inflammations. — Conjunctivitis may be primary or secondary; the 
latter arising by extension, or occasionally by infection via the blood- 
stream. Prolonged irritation by mechanical or chemical agents may 
occasion a true inflammation, but to these factors is almost invariably 
added the action of bacteria, of which many different forms have been 
noted. The principal ones are Morax-Axenf eld's organism, Koch- 
Weeks' bacillus, gonococcus, pneumococcus, diphtheria and pseudodiph- 
theria bacillus, Micrococcus catarrhalis, streptococcus, Bacterium xerosis, 
and Bacillus coli. The pathological changes are congestion and edema 
of the subepithelial layer, followed by hyperplasia of the adenoid tissue 
and infiltration. The epithelium is swollen, softened, becomes opaque 
and desquamates, leaving erosions or ulcerations. The process may be 
catarrhal, or exudative — serous, purulent, or pseudomembranous. There 
are several special forms of inflammation hypertrophic in character, 
such as trachoma, which may be classified as subacute or chronic. 

Acute Catarrhal Conjunctivitis. — In this condition there is swelling, 
redness, and a profuse thin discharge, arising to some extent from the 
diseased membrane, but chiefly from the overproduction of tears. The 
redness is greater at or near the canthi. The process may go over into 
acute purulent conjunctivitis, in which the discharge is purulent almost 
from its inception. The gonococcus is the commonest cause of the 
frank purulent conjunctivitis, particularly in the newborn. The con- 
junctiva and lids in this case are much swollen, and hemorrhages may 
occur, and there is a profuse yellow or greenish discharge. This form 
of inflammation frequently spreads to the cornea or uveal tract. 

Pseudomembranous conjunctivitis is usually due to the diphtheria 
organism, but may be caused by other germs. There is much infiltra- 
tion and induration of the subepithelial tissues, and upon the surface a 
patchy or continuous membrane may form, beneath which ulcers 
arise. 

Special Forms. — Spring catarrh, or vernal conjunctivitis, is a 

chronic recurring hypertrophic inflammation of unknown cause, char- 
acterized by the production of rather flat excrescences upon a smooth, 
hard conjunctiva. The appearance of the surface is as if a thin film of 
milk were spread upon it, a condition said to be due to hyalinization 
below the epithelium. The excrescences are made up of hyperplastic 
epithelium and connective tissue, the latter being quite homogeneous or 
hyaline; in this overgrowth eosinophiles are common. Ulcerations sel- 



THE EYE 



1015 



dom appear in this disease. The secretion is tenacious, yellowish, 
and may be very profuse. 

Follicular conjunctivitis is a subacute or chronic, slightly com- 
municable hypertrophic inflammation characterized by hyperplasia of 
lymphatic tissue producing elevated granules or follicles, usually follow- 
ing the course of the conjunctival folds. This seldom leads to any cica- 
trization, although there is a sort of capsule about the lymph-follicles. 

Trachoma is a chronic communicable hypertrophic conjunctivitis 
characterized by the production of papillary granulations, connective 
tissue overgrowth, and cicatrization, with signs of mild exudative in- 
flammation. These growths appear chiefly upon the lid and at the 
fornix, and contain the so-called " trachoma bodies," nodules of hyper- 
plastic lymphatic tissue surrounded by a fibrous and vascular capsule. 




Fig. 487. — Trachoma, showing round, opaque bodies in upper and lower lids. "Sago- 
grain" type. From a photograph. Frequent type seen in children (Henry T. Brooks). 

The marginal zones of the " bodies" are small and lymphoid, while in 
the center there are large lymphoid cells with granular nuclei, and 
frequently the trachoma "cell inclusion," a hyaline body with a bit 
of chromatic material in it. By some these are said to be like dip- 
lococci. Most observers now put them among Prowaczek's Chlamy- 
dozoa, while some place them among the Protozoa. Many doubt their 
etiological relation, as they have been seen in gonorrheal conjunctivitis. 
Influenza bacilli or closely associated species have been found in 
trachoma. At all events, the cause of the disease is not yet known, 
and most observers believe that the infective agent belongs to the 
filterable viruses. Attempts at cultivation resulted in the develop- 
ment of minute bodies of indefinite morphology. The virus is present 
in the tears, and seems infective at any time in the course of the disease. 
It is infective for monkeys. Exposure to a temperature of 56°C. for 
thirty minutes or to drying for one hour destroys the virus. 

The " trachoma bodies" undergo cicatrization and involve the 
whole lid, and sometimes the bulbar layer, even to the production of 
entropion in the former, or pannus (granulation tissue) in the cornea. 



1016 



A TEXT-BOOK OF PATHOLOGY 



P annus is a hyperplastic vascularizing growth of the surface of 
the cornea due to superficial ulcerative processes. The chief causes 
are trachoma and phylctenular disease. The lesion proceeds from the 
limbus inward, lying between the epithelium and Bowman's mem- 
brane, and consisting of cellular infiltration and capillaries, the former 
preceding the latter. When Bowman's membrane is destroyed the 
corneal matrix is infiltrated and opacity results. 



a/ 




Fig. 488. — Trachoma of the retrotarsal fold: a, Follicle; b, diffuse infiltration; c, Henle's 
gland with goblet-cells; d, lymph-vessel Jilled with leukocytes; X 30 (Holden). 

Parinaud's conjunctivitis is a severe condition with considerable 
swelling and papillary granulations on the tarsal layer, associated 
with signs and symptoms of general infection. The disease has been 
ascribed to a leptothrix, to be found in areas of necrosis in the sub- 
epithelial tissues. An enlargement of the preauricular glands occurs 
so often in this condition that it acquires a diagnostic significance. 

" Pink-eye" is an acute catarrhal and. mucous conjunctivitis due to 
the Koch- Weeks' bacillus. 

Angular conjunctivitis is a contagious condition due to the diplo- 
bacillus of Morax and Axenfeld, characterized by scanty discharge, 
congestion of the caruncle, and, microscopically, by epithelial multipli- 
cation and desquamation on the tarsal side, with ingrowth thereof at 
the edge of the cornea. 

Phlyctenular conjunctivitis is now believed to be an atypical tuber- 
culous process, and is commonly found in association with tuberculosis 
elsewhere. It is also frequently associated with eczema. There are 
small papules formed by the accumulation of lymphocytes under the 
epithelium; these may become pustular, or break down to become 
ulcers. The condition is commonest on the bulbar layer, and the 
cornea is frequently involved. 

Xerosis is a condition of chronic atrophic inflammation and cica- 
trization of the bulbar conjunctiva. The two layers may be bound 
together, and there is frequently a dry scaly membrane on the free 
surfaces. The lesion may follow granular or exudative conjunctivitis 
especially when adhesive cicatrization has replaced superficial defects 
but a primary form seems to occur, alleged to be due to the xerosis 



THE EYE 



1017 



bacillus although this is quite doubtful; the latter type is favored by 
malnutrition or prolonged exposure to sunlight. 

Tuberculosis is usually secondary to tuberculosis in the vicinity, 
but may be primary, as a miliary tubercle or small ulcer. Occasionally 
caseous masses occur, or a hypertrophic lesion like lupus may arise. 

Syphilis. — Characteristic lesions of all three stages have been seen 
in the conjunctiva. 



Fig. 489. — Phlyctenular conjunctivitis (Children's Hospital; (de Schweinitz). 



Pinguecula. — This is a pale yellow triangular chronic thickening 
of the conjunctiva at the margin of the cornea. This is not a mass of 
fat, but a proliferation of yellow elastic tissue, and a hyaline degeneration 
of this and fibrous tissue. 




Fig. 490. — Symblepharon, the sequel of purulent conjunctivitis (from a patient in the 
Philadelphia -Hospital) (de Schweinitz). 



Pteryium is a hypertrophy of the conjunctiva in triangular shape, 
proceeding from the palpebral fissure toward the center of the cornea. It 
is probably due to continued local irritation. Destruction of Bowman's 
membrane and opacity of the cornea results. The fold is made up of 
epithelia, beneath which are lymphoid cells and new blood-vessels. 

Symblepharon is the adhesion between the bulbar and tarsal 
conjunctiva due to continued irritation or chronic inflammation. It is 
a frequent sequel of burns. 



1018 



A TEXT-BOOK OF PATHOLOGY 



Tumors. — Fibromata, papillomata, and lipomata are among the 
common benign growths, and teratomata have been seen. Angiomata 
are common in early life, and may be either simple nsevi or of a sar- 
comatous nature. Sarcomata are not common, but develop from pig- 
mented spots at the edge of the cornea. They are exceedingly vascu- 
lar. The most interesting one is the alveolar sarcoma, or endothelioma, 
which some observers consider epithelial in nature. Epithelioma is the 
commonest tumor in this locality, and is a rapidly growing squamous 
cell growth. Carcinoma may arise from the caruncle. 

Cysts may be lymphangiectatic, or as the results of obstruction to 
glands. Occasionally cysts arise by invagination of epithelium in the 
submucous tissue by reason of inflammation or injury. Such folded-in 
cells continue to secrete fluid and cause cystomata. Cysticercus and 
filarial cysts have been observed. 

LACHRYMAL ORGANS 

The lachrymal sac may be the seat of acute inflammation (dacryo- 
cystitis) by extension through the ducts, by injury, or rarely, primarily. 
Inflammation, either acute or chronic, may obstruct the flow of tears 
and distend the sac. Chronic inflammation around the canthus is 
usually associated with inflammation of the nasal duct and obstruction 
of tears. Inflammation of the nasal duct may be an extension process 
from the nose. Occlusion of the duct is temporary in acute inflam- 
mations, but stenosis may occur as the result of long-standing nasal dis- 
ease. Obstruction to the proper outflow through the nasal duct causes 
an accumulation of tears in the sac thus forming an excellent place for 
organisms to grow, and supplying a culture wherewith to aggravate any 
coexisting conjunctivitis, especially if it be ulcerative. Dacryo-adenitis, 
or inflammation of the lachrymal gland, is of any form, and arises from 
injury or by extension from the conjunctiva upward along the canaliculi. 
This body is sometimes the seat of mixed tumors which w T hile of slight 
malignancy, jeopardize the bulb and should be removed. 

CORNEA 

Keratitis, or inflammation of the cornea, is usually primary, but is 
occasionally secondary to conjunctival conditions. It assumes two 
forms, ulcerative or superficial, and non-ulcerative or interstital. The 
latter always causes opacity, varying directly according to the severity 
of the infiltration. Ulceration always results in scar formation, as 
do the higher grades of infiltration. Milder grades of the latter may be 
removed without leaving any serious visual defect. 

The microscopical changes in keratitis are swelling and degenera- 
tion of the corneal corpuscles, about which there may be some prolif- 
eration of these cells and an infiltration of a few leukocytes. At the 
margin of the cornea there is always vascular injection and very early 
appearance of new capillaries growing in the direction of the lesion. 

Infiltration may go on to suppuration and perforation. When ulcer- 
ations or suppurations perforate, there is an escape of aqueous and re- 
lease of pressure with forward dislocation of the iris or even of the lens. 
The iris may adhere to the edges of the rupture (anterior synechia), and 



THE EYE 



1019 



the contact of the lens with the lesion in the cornea may cause anterior 
polar cataract. Perforation of an infected corneal lesion may lead to 
pus in the anterior chamber, hypopyon. Healing of deep corneal defects 
occurs by fibrous tissue, leaving opacities. In healing the cornea some- 
times is flattened instead of having its normal curvature, a facet being 
formed; again, a protrusion may occur where the newly formed tissue 
is not able to resist the intra-ocular pressure — staphyloma. Keratitis 
may lead to panophthalmitis. 

Interstitial Keratitis. — This condition, commonly due to general dis- 
eases like syphilis and gout, is characterized by the formation of opaque 
mottlings, or a complete ground-glass appearance of the cornea. It is 
caused by a cellular infiltrate without tendency to abscess formation. 
One variety, the marginal, is densest around the scleral insertion, 
and, another form, the vascular, shows a production of new blood- 
vessels (pannus) growing in from the periphery. The epithelium may 
be eroded or hypertrophic. 




Fig. 491. — Perforating ulcer of the cornea with incarceration of iris (from a photomicro- 
graph) (de Schweinitz). 

Bullous keratitis is a condition in which crops of vesicles appear 
associated with considerable pain. Herpes of the cornea is of the same 
nature, but the vesicles are smaller and the cornea may be anesthetic; 
one variety is due to a disease of the fifth cranial nerve. The lesion is a 
dropsical collection in the outer layers of the structure, usually beneath 
Bowman's membrane. Another condition associated with the disease 
of this nerve, with its consequent loss of sensibility of the cornea, is the 
so-called neuroparalytic keratitis, an ulcerative process limited to the 
cornea and prone to suppuration. 

Ulcerative keratitis may be secondary, or arise as the result of infil- 
tration in the cornea itself > The ulcers may originate in a superficial 



1020 



A TEXT-BOOK OF PATHOLOGY 



traumatic loss of tissue upon which bacteria are implanted, or by the 
sloughing off of the epithelium over an infiltrated or edematous patch in 
the cornea. About such an area, a zone of leucocytes shortly appears 
from which a purulent exudation may be derived. The process may 
continue inward until Descemet 's membrane is reached, being occasion- 
ally stopped at this layer. More commonly destruction of this tissue 
occurs and a complete perforation is produced. When only the anterior 
epithelium and Bowman's membrane are involved the defect may be 
completely healed without maculse, the epithelium growing over first, 
the corneal corpuscles making fibers later. Except in the most severe 
grades there is only a pericorneal congestion and little tendency to 
pannus. 

Phlyctenular keratitis, associated with the similar disease of the 
conjunctiva, is characterized by the production of papules composed 
of lymphoid cells, which tend to soften and form ulcers which spread 
toward the corneal center, surrounded and followed by new blood- 
vessels. They heal from the margin, but opacity always results. 
Perforation or extension by continuity may occur. 

Suppurative keratitis may be diffuse or localized. In either case ul- 
ceration with perforation is likely to occur. Serpiginous ulcer, due 
frequently to the pneumococcus, is perhaps the most common va- 
riety. The ulcer spreads superficially rather than in depth, but per- 
foration is not uncommon. Discrete abscesses may occur in the 
cornea. 

Keratomalacia is an acute degenerative (fatty) change of the corneal 
epithelium, usually associated with inflammation, occurring in debili- 
tated children. Sluggish ulcers may arise. 

Syphilis may appear as an acute or subacute infiltrative lesion, and 
gumma is known in this locality. 

Tuberculosis is usually secondary to adjacent tuberculosis, and 
appears as an infiltrative and sclerosing process. 

Leprosy appears as a nodular keratoconjunctivitis with a histology 
comparable to that of leprosy of the skin. 

Arcus senilis is a hyaline degeneration of the cornea in annular 
form near the periphery, but separated clearly from the sclera. It 
usually begins above and extends laterally. I.t is a pale gray band at 
first, but later becomes opaque, silvery, or gray white. It is said to be 
due to faulty nutrition when the circumferential vessels are diseased. 

Wounds of the cornea may be superficial, leading to simple destruc- 
tion of tissue, which is repaired without scar or followed by ulceration 
and opacities; or penetrating, in which case deeper structures are usually 
involved and the humors are infected or may escape. Wounds leading 
to ulceration if associated with extensive fibrous tissue repair may lead 
to pterygium or, rarely, to symblepharon. 

Tumors are exceedingly rare in the cornea. Papilloma and myo- 
fibroma have been reported. 

Cysts arise in the cornea under the same conditions as in the con- 
junctiva. 

The Anterior Chamber. — Inflammation of Descemet's membrane 
may arise by extension from inflammation of contiguous structures 



THE EYE 



1021 



and presents the changes observed in other serous membranes. Pus 
(hypopyon) arises in the anterior chamber from any sort of infected 
corneal ulcer, wound, etc. 

SCLERA 

Episcleritis . is an acute superficial hypertrophic and infiltrative 
inflammation of the exposed part of the sclera, characterized by low 
dark red granulations or papules, consisting of lymphoid and poly- 
nuclear cells and accompanied by small hemorrhages and edema. This 
heals without cicatrization. The conjunctiva is movable over these 
excrescences and is 1 injected. 

Scleritis is a deep, diffuse, infiltrative, overproductive inflammation 
of the sclera, usually of the exposed part, arising, after exposure, in 
rheumatic, gouty, and syphilitic individuals. It assumes a nodular form 
associated with hemorrhage and edema. Healing occurs by cicatriza- 
tion which leads to thinning and weakening, in consequence of which 
scleral staphyloma results. One syphilitic form grows as a pericorneal 
band, consisting, microscopically, of young granulation tissue. 

The importance of injury to the sclera depends upon whether or 
not a puncture has been effected with disturbance of relation of the 
various intra-ocular structures, and the introduction of germs. In 
the presence of these unfavorable factors there may be escape of the 
ocular contents or suppuration while if recovery occurs healing will take 
place by scar tissue of course, and lead to destruction of the ciliary body 
or lens and to weakness of the ball membranes. Tension by scar tissue 
upon the ciliary body may cause increased intra-ocular pressure. The 
sclera may be ruptured by a blow upon the eye. 

Tuberculosis, syphilis, tumors, and cysts are exceedingly rare in the 
sclera. 

THE CRYSTALLINE LENS 

Congenital abnormalities of the lens take the forms of cataract, 
false position, or abnormal curvature, or it may be involved in a colo- 
boma. Opacity of the lens (cataract) is the principal acquired patho- 
logical change. This is due to hyperplasia of the capsular epithelium 
or degeneration of the internal fibers. When due to the former it is 
called capsular, when to the latter, lenticular, cataract; both may be 
involved, capsulo-lenticular. 

Capsular cataract is usually encountered near the middle of the 
anterior surface, and is ascribed to some form of insult from the front 
of the eye, in response to which the lens capsule proliferates, the epi- 
thelium first becoming reduplicated, then stratified. An opaque degen- 
eration of the epithelial fibers accompanies or follows the capsular 
change. Posterior capsular cataract is either congenital, due to the 
remains of the hyaloid artery, or secondary, due to long-standing dis- 
ease of the posterior segment of the eyeball, especially in the choroid. 

Lenticular cataract is a degeneration involving in part or wholly the 
fibrillar structure of the lens, rendering it opaque. The traumatic 
variety is understood, but those due to constitutional disease, inflam- 
mations in contiguous structures, or senility are vague in etiology. 



1022 



A TEXT-BOOK OF PATHOLOGY 



It is said that the essential feature in all cataracts is an altered tension 
in the capsule and nucleus, which permits invasion of the fibrous struc- 
ture by the aqueous humor. The first change seems to be a shrinking 
of the lens, shortly followed by swelling as the fluid penetrates. This 
fluid collects in globular masses as do also the remains of degenerated 
fibers. The capsule may be in natural condition or proliferating. 
The interior of the lens may soften to a liquid mass in which the nucleus 
may float or sink (Morgagnian cataract). After the lens has softened 
some shrinking is noticeable, due probably to beginning absorption. 

There are various forms of cataract recognized by ophthalmologists, 
depending upon the arrangement of the opaque areas. Their path- 
ology is essentially the same however. 

A cataract of the lens fiber may arise from any trauma which so 
affects the capsule as to permit the invasion of the aqueous. It may 
be a part of or accompany an inflammation of contiguous tissues. 

Dislocation, or luxation, of the lens may occur from trauma or from 
disease. In the former case the lens may penetrate the vitreous or 
anterior chamber, or, by rupture of the iris and of the insertion of the 
cornea, to a position under the conjunctiva. Pathological luxation may 
be due to degeneration of its suspensory ligament, or in atrophy after 
cataract. 

THE VITREOUS HUMOR 

Hemorrhage into the vitreous arises only from injury or disease of 
surrounding tissues. In the latter it may arise from simple inflam- 
mation, but more often it is the result of dyscrasia or diseased vessel 
walls. 

Chemical changes in the vitreous are due to disease of the choroid 
or retina. They comprise infiltrates of phosphates, fat, cholesterol, or 
osseous matter. The last supervenes sometimes upon overgrowth of 
connective tissue from chronic retinitis or choroiditis. Opacities usually 
arise as a result of these chemical changes. Degenerative changes take 
the form of fibrillation and liquefaction. The mass soon shrinks by 
loss of fluid. 

Inflammation is secondary to disease in retina, choroid, and ciliary 
body. Microscopically, there is mild leukocytic infiltration with coarse 
fibrillation. After inflammation or hemorrhage into this humor, new 
blood vessels may arise from the choroid and traverse the central area. 

The vitreous may escape in punctured wounds, permitting hemor- 
rhage and detachment of the retina. Foreign bodies, filaria, and cysti- 
cercus cysts have been found in the vitreous. 

THE IRIS 

Congenital abnormalities of the iris take many forms, affecting 
its continuity or pigmentation. Affections of the continuity embrace 
obstruction of the pupil by persistence of the anterior vascular capsule 
of the lens which occupies the pupillary space in the embryo; dy scoria, 
irregularity of the pupil and distortion of the iris muscles; polycoria, 
the existence of several openings in the iris; corectopia, or incorrect 
position and shape of the pupil; and coloboma, taking the form of a 



THE EYE 



1023 



linear defect extending from the pupil even to the ciliary body. Occa- 
sionally the coloboma may be very extensive or the iris absent entirely, 
this is aniridia or iriderenia. 

Abnormalities of pigmentation consist of its absence, albinism; or 
excess, melanosis; or of mixtures of colors, especially eyes of different 
colors, known as heterochromia. 

Atrophy of the iris occurs as the result of recurrent acute attacks of 
inflammation, or by interference with its blood-supply, as from prolonged 
intra-ocular pressure or traction upon the ciliary body. It may occur 
as a result of senility. The pathological changes embrace fibrous and 
hyaline deposits particularly in and around the blood walls, irregularity 
or loss of pigment, and at times a hypertrophy of the endothelium 
reflected from Descemet 's membrane, a sort of replacement hyperplasia. 

Hyperemia of the uveal tract may be an early stage of inflam- 
mation, or the result of disease in adjacent tissues. 

Anemia is merely a part of general anemia. 

Inflammations of the iris may be acute or chronic, but are always 
exudative in character. The acute may be serous, purulent, simple 
plastic, or combinations of these. 

In serous iritis the membrane is swollen, congested, and there is a 
watery exudate in the anterior chamber which may or may not contain 
shreds of lymph. This condition is prone to spread to the ciliary body 
and choroid, thence to the vitreous, which may develop opacities. 

In plastic iritis, the most frequent form and usually associated with 
inflammation in the rest of the uveal tract, the process is of greater in- 
tensity, fibrinous exudate appears, and tabs of lymph are found upon the 
iris and Pescemet's membrane; synechia may be found. Synechia may 
attach the iris to the anterior surface of the lens around the pupillary 
opening (annular synechia), or the whole iris may become fast (total pos- 
terior synechia). The exudate is at times extensive enough to span the 
pupil. Under these conditions of synechia and closure of the pupil the 
iris becomes fixed, and outflow of the aqueous humor from the ciliary 
processes and posterior chamber through the pupil into the anterior 
chamber is hindered. Then increased intra-ocular pressure arises. 
This inflammation practically always involves also the rest of the uveal 
tract. 

Purulent iritis may succeed upon the foregoing, and in its spread and 
results differs little from it except that it is more rapid and extensive. 
Pus in the anterior chamber (hypopyon) is an almost constant feature. 

The pathogenesis of these forms of iritis is essentially the same. 
The process begins as a congestion and infiltration, usually in the loose 
layer of the iris, causing hyperplasia or rupture of the endothelium, 
with a collection of exudate upon this surface that may extend back- 
ward to the ciliary body and choroid. There is injection of the peri- 
corneal zone. Where the condition is repeated or if of a low grade and 
not purulent, distortion and atrophy of the membrane arise so that 
irregularity of shape and pigmentation are seen. 

Primary iritis would be due to direct introduction of the virus but as 
this is extremely rare, most cases are explained upon the ground of ex- 
tension from nearby structures or metastasis; such indeed is probably 



1024 



A TEXT-BOOK OF PATHOLOGY 



the usual genesis of all inflammation within the eye. Iritis can commonly 
be traced to rheumatism, gout, syphilis, gonococcal infection, diabetes 
and tuberculosis while a certain number of cases remain to be explained 
on the basis of focal infection, maybe of tonsil, of genito-urinary or 
gastro-intestinal tract or of teeth; iritis may occur in acute sepsis. 

Tuberculosis of the iris is probably always secondary, and appears 
as a diffuse seroplastic thickening, as miliary tubercles, or as a large 
caseous mass. The miliary form appears as disseminated yellow dots 
which soon coalesce and extend to the ciliary body. Caseous tubercu- 
losis takes the form of a rapidly growing tumor-like mass composed of 
fused tubercles, which tends to grow outward and rupture the eyeball. 
Tuberculosis of the iris is usually unilateral. It is a disease of 
youth. 

Syphilis of the iris appears as a secondary or tertiary manifestation 
in the form of an acute seroplastic inflammation, or as gumma. The 
former consists of specific arteritis and peri-arteritis with round-cell infil- 
tration and fibrinous exudate, all of which processes are usually combined 
in nodular fashion near the free edge of the iris. Gummata are commonly 
found on the pupillary or ciliary borders and do not differ from gummata 
elsewhere. 

Tumors. — Primary tumors are exceedingly rare, melanosarcoma 
being the principal variety. Occasionally angiomata are seen in the 
form of naevi, which may be pigmented and give rise to sarcoma. It 
is said that endo- and perithelioma may arise from them. 

Cysts. — Parasitic and dermoid cysts have been reported. Some- 
times cysts arise from bits of epithelium which have been forced into 
the iris by violence, as is the case with the cornea. 

THE CILIARY BODY 

Atrophy of the ciliary body is secondary to inflammation, and 
occurs in old age. The processes become flattened and the secretory 
functions disturbed. 

Inflammation, or cyclitis, is seldom a solitary process, usually 
being a part of or secondary to iritis, as iridocyclitis and is caused by the 
same factors. The process is commonly plastic, although it may be 
purulent. The condition affects the substance of the body and the ex- 
posed part within the posterior chamber. The organization of the fibrin- 
ous exudate causes the anterior walls of the posterior chamber to adhere to 
the lens (synechia) , and the inflammatory process invades the lens cap- 
sule and vitreous. In severe cases the last-named structures are infil- 
trated, degenerated, and contain opacities. The lens may be dislocated 
and the uveal tract drawn inward from the sclera by traction of fibrous 
tissue. The retina may be detached. These lesions cause such disturb- 
ance of nutrition that the bulb begins to soften and phthisis bulbi results. 

A chronic form of iridocyclitis, sometimes called serous uveitis, 
affects the anterior portion of the eye by extending to Descemet's 
membrane and filling the anterior chamber with a fluid containing bits 
of fibrinous and cellular exudate. Microscopically the lesion is a 
hyperplasia of the ciliary epithelium with round cell infiltration of the 
iris and corneal insertion. 



THE EYE 



1025 



Tuberculosis assumes the same forms as in the iris. 

Syphilis of the ciliary body alone is rare, but gummata are reported. 

Tumors. — Glioma is the commonest tumor and arises from the 
retinal segment of the ciliary body. Sarcoma, either simple or melanotic, 
sometimes occurs. 

Cysts are very common, and are said to be due to epithelial inclu- 
sions. 




Fig. 492. — Traumatic iridocyclitis. Diffuse infiltration of the iris and ciliary body (de 

Schweinitz) . 

THE CHOROID 

Hemorrhage in the choroid is common because of the high vascu- 
larity of the membrane. Minute hemorrhages occur under various 
conditions, but their exact cause is not known. They may lead to 
atrophy of the membrane. Large hemorrhage is due to trauma. 

Atrophy of the choroid may be due to hemorrhage, inflammation, 
or nutritional disturbances. Sometimes collections of so-called "colloid " 
matter are found among the elastic fibers. 

Wounds and ruptures are serious because they usually cause sepa- 
ration of the retina and escape of the vitreous to a position beneath 
the sclera. The choroid may be detached from the sclera by hemor- 
rhage or exudation. 

Inflammation.— In considering inflammation of the choroid it is 
difficult to separate this membrane from the ciliary body and iris in 
front, and the retina within. Disease arising in any one of these parts 
may extend to the others (uveitis), and when all these contiguous struc- 
tures are invaded the chances of full repair are small. The bulb and 
its surrounding tissues are swollen and infiltrated. 



1026 



A TEXT-BOOK OF PATHOLOGY 



Choroiditis is an exudative process, serous, plastic, or suppura- 
tive in type. Its causes, aside from involvement by extension, are 
auto-intoxication, gout, rheumatism, syphilis, tuberculosis, and, occa- 
sionally, the acute infections, like erysipelas or typhoid fever. It is 
commonly associated with inflammation of the retina, although one 
coat may be affected without the other. 

Serous choroiditis appears suddenly, with swelling of the membrane 
and opacity of the vitreous. 

Purulent choroiditis follows the same course, but the exudate as a 
cloudy mass soon infiltrates the ciliary body and iris, and collects in the 
anterior chamber. The vitreous and retina are shortly involved. 

Chronic choroiditis may be diffuse or disseminated. The dissemi- 
nated forms occasion rounded irregular patches of infiltration over the 
fundus which spread and coalesce; the retina over them becomes hazy. 
These infiltrations may dissolve, leaving in their place pale areas of 
fibrosis which soon take up pigment. These areas may spread by de- 
generation and connective-tissue growth even after the active inflam- 
mation has ceased. They may have calcareous deposits in them. 
Retinal atrophy over them may result. 

Diffuse choroiditis is characterized by the appearance of large yellow 
coalescing plaques of exudate over which the retina is edematous. 
Atrophy of vessels and retinal elements, even of the optic nerve, results. 

In acute and chronic cases of choroiditis contiguous structures are 
usually involved. After choroiditis, especially of recurrent nature, 
the internal surface tends to form granulation tissue with exuberant 
growth into the vitreous, with, first, hypertrophy, then atrophy, of the 
retina. The type of infiltrating cell in both acute and chronic in- 
flammation, except, of course, the suppurative, is that of the lympho- 
cyte series. 

Tuberculosis of the choroid is commonly of the miliary variety, 
but a diffuse infiltrative or large caseous tuberculosis is reported. 
Miliary lesions seem to occur mostly on the outer surface, while the in- 
filtrative or caseous processes prefer the inner layers. 

Syphilis usually causes a serous or plastic choroiditis, but the cho- ■ 
roid is seldom involved without the retina. 

Tumors. — Sarcoma is the most important, and is usually of the 
melanotic variety, a very malignant growth giving many metastases. 
Among the varieties met with there may be melanotic, simple, alveolar, 
or angiosarcoma, and, related to the last, peri- and endothelioma. 

Carcinoma occurs only as a secondary growth, as does glioma. 

THE RETINA 

Anemia is due to general anemia or obstruction of the central retinal 
artery by thrombosis or sclerosis. Fatty degeneration may follow it. 
Blindness results at once from any sudden stoppage of the artery, such 
as from embolism or spasm. 

Active hyperemia is due to long-continued irritation, inflammation, 
or high arterial tension. 

Passive hyperemia is due to: (a) conditions in the eye itself, glau- 
coma, choked disk; (6) conditions in the orbit, cellulitis, tumors; and 



THE EYE 



1027 



(c) conditions away from the eye, heart disease, cranial growth, sinus 
thrombosis. Grossly, there is lengthening, distention, and tortuosity 
of the arteries and veins of the eye-ground. Hemorrhage from such 
vessels may occur. 

Hemorrhage. — Retinal hemorrhage occurs from hyperemia, trauma, 
and vascular disease; in the last are included thrombosis, angiosclerosis, 
and acute angitis. The diseases in which hemorrhage is apt to occur 
are nephritis, diabetes, gout, rheumatism, general arteriosclerosis, 
anemia, leukemia, purpura, acute infections, and certain poisonings. 
The hemorrhages appear as radiating red splotches in the neurofibrillar 
layer, or they may take the form of irregular extravasations into or 
beneath the retina, or even into the vitreous. The blood may be ab- 
sorbed and leave areas which undergo fatty degeneration, spots of blood- 
pigment remaining. Larger hemorrhages may leave an organized clot. 

Atrophy is a consequence of prolonged inflammation leading to 
disturbance of nutrition, or is a senile change. A similar change in the 
choroid is usually found. The microscopical alteration consists in a 
shrinkage of the cellular layer with separation of the rods and cones. 
The cells and fibers show some fatty metamorphosis, and fibrous tissue 
increases, particularly between the retina and choroid. Pigment is 
decreased. 

Detachment of the retina is the separation of the membrane by 
splitting between the pigmented layer and that of rods and cones. It 
is a serious progressive condition due to injury, to shrinkage of the 
vitreous, to rapid lengthening of the antero-posterior diameter of the 
bulb, or to disease of the retina whereby fluid diffuses into its deeper 
layers. These factors are favored by inflammations, tumors or scars 
within the eye. The membrane remains uncertainly suspended in the 
vitreous chamber. 

Inflammation. — As is the case of inflammation elsewhere in the 
inner eye, retinitis is infiltrative and exudative. The simplest form is 
little more than a marked edema of the retina, but deserves to be placed 
among the inflammations because there may be cellular infiltration 
associated with edema. Regeneration may in favorable cases be com- 
plete after this mildest grade. Serous retinitis may proceed to 

Purulent retinitis, a condition usually due to perforating wounds, 
but which also arises metastatically. The process is a swelling with 
infiltration of pus throughout the retina, which is soon detached, and 
then the vitreous and anterior segment of the eye are attacked. Hem- 
orrhage frequently occurs. Panophthalmitis always supervenes. 

Albuminuric retinitis, a characteristic change in nephritis, is really 
a neuroretinitis. There is swelling, reddening, and obscurity of the 
nerve-head, around which spot are radiating linear hemorrhages and 
pale anemic coalescing areas, which are hyaline or fatty degenerations. 
The vessels are distended and tortuous. The minute changes are those 
of chronic retinitis and marked sclerosis of the vessels. Degeneration 
of the nerve-fibers also occurs. 

Diabetic retinitis is a hemorrhagic process. The optic nerve-head 
is less apt to be swollen, and the retina in general is more normal in 



1028 



A TEXT-BOOK OF PATHOLOGY 



appearance than in the preceding, save for irregular or linear hem- 
orrhages. There is, nevertheless, a mild chronic retinitis. 

Chronic retinitis assumes many forms for the clinician, but the his- 
tological changes are essentially the same in all. There is cellular infil- 
tration of the vitreous layers with fibrous tissue growth inward from 
the parts near the choroid. In the infiltrate are endothelial cells of 
obscure origin, probably from the adventitia of blood-vessels, which tis- 
sue is actively hyperplastic. Giant cells are common. In the organiza- 
tion of chronic retinitis the choroid may become adherent and the inner 
retinal fibrillary layers become wrinkled and proliferative, even to 
the extent of showing granulation tissue. The fibrous layer of the retina 
may also undergo liquefaction or fatty degeneration. In diffuse retinitis 
these changes are more or less evenly distributed, but there is a dis- 
seminated form in which patches of chronic inflammation occur, and 
in this variety the internal overgrowth of tissue is commonest. 

Retinitis pigmentosa, or pigmentary degeneration of the retina, is a 
chronic progressive atrophic process beginning at the equator or ante- 
rior thereto and proceeding backward, characterized by the deposit in the 
outer layers of the membrane of black pigment in splotches with exten- 
sive radiations. The retina about the optic disk is the last part to be 
affected. Under the microscope there is found obliterating endarteritis, 

with hyaline degeneration and deposit of 
pigment in the vessel walls, and disappear- 
ance of the normal pigment. The late stage 
will show disappearance of the nodes and cones, 
fibrous tissue overgrowth about the ganglion 
cells and nerves, and distortion of the optic 
head. 

Tuberculosis of the retina is usually sec- 
ondary to adjacent tuberculosis. It is of 
the miliary variety. 

Syphilis of the retina in an acute or chronic 
form assumes the vascular proliferative char- 
acter peculiar to this infection. 
Fig. 493.— Glioma of retina Tumors. — Glioma is the only primary 
(patient in the University Hos- tumor certainly arising in the retina. It is 

pital) (de Schwemitz) . _ f .„ . , 7 

commonly met with m children, and may be 
due to congenital defect. It is a progressive tumor usually growing 
forward through the eyeball and presenting a sloughing cauliflower-like 
mass externally. This tumor is prone to give metastasis to bones and 
glands, is very cellular and rich in blood-vessels, and most often 
originates from the inner nuclear layer of the retina. 

Angiomata and fibromata are reported/but their origin is not certain. 

SYMPATHETIC OPHTHALMITIS 

This is the term applied to inflammation of one eye after disease or 
injury to the uveal tract, retina or nerve head of its fellow. The period 
at which this occurs varies from about two to six weeks but may be longer. 
Sympathetic ophthalmitis usually takes the form of a subacute remitting 
or recurrent plastic or serofibrinous uveitis, but certain cases begin as a 




THE EYE 1029 

papillo-retinitis or iritis. Inasmuch as inflammation of any one of the 
divisions mentioned may spread to the others, a panophthalmitis usually 
results. Pathologically the secondary lesion is similar to the primary 
but is perhaps more infiltrative and hyperplastic. Posterior synechia, 
corneal opacity, staphyloma, or glaucoma may ensue. Sympathetic 
ophthalmia may follow perforating wounds in the ciliary region, especi- 
ally if a foreign body be retained; old retinitis with calcification acting 
as a foreign body; long-standing iridocyclitis; luxation of lens; pressure of 
an artificial eye; or irritation of the optic nerve stump by fibrous tissue 
after enucleation. The definite cause is not known, but is variously 
ascribed to some special micro-organism, to reflex nerve irritation and 
to a toxin which has a special affinity for the uveal tissue, but all of these 
suggestions fail to explain the genesis or the various incubation periods. 
Recently it has been shown that the uveal pigment may act as an antigen 
and, when once disturbed in an eye, give rise to a state of sensitization 
against itself whereupon the uveal tract of the opposite eye is involved in 
an anaphylactic reaction. It has been suggested that a tuberculous or 
syphilitic taint may predispose to sympathetic ophthalmitis. 




I - 

Fig. 494. — Section of optic nerve-head containing a deep glaucomatous excavation, 
the so-called kettle-shaped excavation: r, Retina; ch, choroid; s, sclera; c, cup or excava- 
tion, pushing back lamina cribrosa (de Schweinitz). 

GLAUCOMA 

The normal intra-ocular tension is maintained by the proper secre- 
tion and escape of the aqueous humor. If its escape be hindered, pres- 
sure rises and glaucoma results. The condition may be considered 
primary when no demonstrable cause exists, and secondary when trau- 
matic or inflammatory disease of the bulb has preceded it. The sec- 
ondary form is due to synechise obstructing the aqueous current be- 
tween the posterior and anterior, chambers, to inflammatory lesions 
of the ciliary body, or to obstruction at the iridocorneal juncture, in- 
cluding the spaces of Fontana or Schlemm's canal. Such lesions either 



1030 



A TEXT-BOOK OF PATHOLOGY 



render the aqueous humor too viscid to filter easily or hinder absorption. 
Primary glaucoma may arise in the apparently healthy eye. Arterial 
disease seems to favor its development. The eye in acute glaucoma is 
swollen, cloudy, injected, lusterless, and the pupil shows a green appear- 
ance. Pathologically the lesions in such eyes are similar in the acute or 
chronic, primary or secondary forms insofar as the glaucomatous process 
is concerned. They consist of cellular infiltration of the uveal tract and 
retina upon which atrophy succeeds in the latter stages. These changes 
will be modified of course by any preexisting lesions that led to the in- 
creased tension. In chronic glaucoma there is progressively increasing 
hardness of the eye, atrophy of the retina, and "cupping of the disk," 
a condition due to posterior staphjdomatous protrusion at the lamina 
cribrosa with degeneration of the optic nerve. 




Fig. 495.: — Ophthalmoscopical picture of papillitis and semidiagrammatical representation 
of a longitudinal section of the nerve-head (de Schweinitz). 

THE OPTIC NERVE 

Hyperemia is found under the conditions given for Hyperemia of 
the Retina. 

Inflammation. — Inflammations affect either the retinal portion of 
the nerve (papillitis) or the extra- or retrobulbar portions. The causes 
of this disease are metastatic in infections, or involvement by continuity 
from the retina, meninges, or orbital tissue. There is also a congestive 
form in cases of vascular obstruction, such as by intracranial new growths 
or increase in the quantity and pressure of the cerebrospinal fluid ; in this 
case there is simple edema and hyperemia. 



THE EYE 



1031 



Papillitis, papillo-edema, or choked disk, is a swelling of the retinal 
end of the optic nerve with indistinctness of its outlines. There may 
be small hemorrhages, sometimes in radial linear arrangement. The 
nerve-head is turbid when infiltration is marked, and minute examina- 
tion reveals edema, round-cell infiltration, and granular degeneration 
of the nerve-fibers. In inflammation of the trunk of the nerve infiltra- 
tion is the same, but one finds proliferation of the endothelial lining of 
the intraneural spaces and degeneration and atrophy of the nerve- 
fibers. The form of papillitis dependent upon increased intracranial 
pressure partakes chiefly of the nature of atrophy, although both this 
and the atrophies of the nerve-head which accompany constitutional 
disease usually pass through a low inflammatory process similar to that 
just given. Atrophy of the optic nerve from conditions not arising 
within the eyeball may be due to pressure by lesions in the orbital 
tissues, or from diseases like paresis and tabes, and poisoning from 
quinin or tobacco. The degenerations and atrophies depend upon the 
production of areas of ischemia because of disease of the blood vessels 
and upon selective action of poisons for certain nerve elements. 

Tuberculosis affects the optic nerve as miliary tubercles in the 
sheath. 

Syphilis takes the form of gumma or neuritis. 

Tumors. — The primary tumors of the nerve are divided into the 
intra- and extradural forms. The former comprise myxoma, fibroma, 
psammoma, endothelioma, and sarcoma. Extradural tumors are 
fibroma, endothelioma, and sarcoma. 

THE ORBIT 

Abnormalities of Position of the Bulb. — The most important 
condition under this heading is exophthalmos or proptosis. This is due 
to swelling of the areolar supporting tissue within the orbit, as from 
inflammation, venous congestion, hemorrhage, or tumors. The results 
are stretching of the muscles and consequent incorrect position of the 
eye in the visual axis; stretching of the optic nerve if the protrusion of the 
ball is greater than the slight amount of slack that the curve in the nerve 
can give, upon which optic neuritis may ensue. If the lids be unable to 
close there may arise conjunctivitis and keratitis with ulceration due to 
the dryness and lack of protection from dust. In exophthalmic goiter 
the proptosis is variously ascribed to a spasm of the muscle of Muller, 
orbital hyperemia, and irritation of the sympathetics. In postorbital 
aneurysmal varices there may be a pulsating proptosis. 

Enophthalmos is sinking in of the bulb when the posterior orbital 
tissues are absorbed, or from a fracture of the skull involving the orbit. 

Inflammations affect the orbital tissue as cellulitis or abscess, and 
arise from injury, extension, or metastasis. Periostitis of the orbital 
bones may arise under the usual causes for this disease. 

Tumors arise from the optic nerve, as above; from the perios- 
teum, fibromata, exostoses, and chloroma; from the ball-supporting 
tissue, angioma, lymphoma, and sarcoma, including endothelioma. 
Epithelioma may arise in the lids. - 



1032 



A TEXT-BOOK OF PATHOLOGY 



THE LIDS 

Edema may be traumatic or accompany ocular inflammation, 
cardio-renal disease, anterior cranial sinusitis or intracranial sinus throm- 
bosis. It occurs in angioneurotic edema and exophthalmic goiter. 

Ptosis is incomplete elevation of the upper lid, and may be due to 
congenital absence of muscle power, or to muscle impairment by palsies 
of the third cranial nerve. 

Inflammation. — Blepharitis, inflammation of the lids, may be a 
simple catarrhal process, but the more chronic cases assume the form 
of a productive conjunctivitis and dermatitis. By organization and 
fibrosis in severe cases the ciliary margin is destroyed and the tear puncta 
either obstructed or rendered useless by thickening or eversion of the lid. 
A chronic conjunctivitis and keratitis may ensue. 

Stye, or hordeolum, is a small abscess in a hair-follicle. A chronic 
granuloma of the Meibomian glands with histology like a tubercle, but 
not of tuberculous nature, is called chalazion. 

Tumors. — Epithelioma, carcinoma, and, occasionally, sarcoma have 
been seen. Of the benign tumors, papilloma, fibroma, and adenoma are 
reported. The glandular tumors arise from sebaceous and Meibomian 
glands. 



CHAPTER XVI 



THE EAR 

ANATOMY 

The external ear consists of the auricle and external auditory canal. 
The former is composed of skin and yellow elastic cartilage. The 
canal is cartilaginous in the outer part, lies within the temporal bone 
for the inner part, and is lined with skin containing sudoriferous and 
sebaceous glands which secrete cerumen. 

The tympanic membrane separates the external and middle ears. 
Externally, this curtain is covered by skin, internally, by a mucous 
membrane between which layers there is a fibrous layer into which the 
malleus is inserted. At the superior portion of the tympanic membrane 
there is an umbrella-shaped section of thinner tissue, Shrapnell's mem- 
brane, supported on either side by strong fibrous folds. Within the 

Elevation ot tympanomastoid semicircular Mastoid antrum 

canal in aditus ad antrum \ Cer 
Oval window 
Canal for tensor tympani muscle 

Osseous Eusta- 
chian tube 
Facial canal at 
point of turn- 
ing backward 
Carotid can a 
Annulus tympanicus 

External auditory meatus 
Glenoid 



Fig. 496. — Section of temporal bone in plane of mastoid antrum. Aditus, tympanum, and 
Eustachian tube, showing direct connection of all these spaces (Barnhill and Wales) . 

membrane, situated in the petrous portion of the temporal bone, is the 
tympanum, or middle ear. Behind it lies the mastoid portion of the 
temporal bone with the cells of which there is a communication; be- 
low it is the roof of the jugular fossa. From the anterior part of the 
floor of the tympanum the Eustachian tube passes downward, for- 
ward, and inward to the^'pharynx, through the canalis musculo-tubularis, 
which also carries the tensor tympani muscle. There is a natural isthmus 
of the tube 2.5 cm. from the pharyngeal ostium. The Eustachian tube 
is lined by ciliated epithelium. Suspended in the tympanum, the chain 
of ossicles is inserted externally into the external tympanic membrane, 
internally into the oval window. The cavity is lined by cuboidal epi- 
thelium. The internal ear consists of a vestibule into which the oval 
window opens, semicircular canals, and cochlea; this is also called the 
labyrinth, and consists of a membranous part lying in a bony cavity of 
the same shape and arrangement. The semicircular canals are disposed 

1033 




1034 



A TEXT-BOOK OF PATHOLOGY 



in the three geometric planes, and the lining is mucous membrane rich in 
branches of the auditory nerve and covered with ciliated epithelium. 
The cochlea, a conical spiral body, lies before the vestibule and contains 
the organ of Corti, the special end-organ of hearing. The auditory, or 
eighth cranial nerve, passes into the ear by the internal auditory meatus 
and divides into branches which go to the cochlea, vestibulum, and 
semicircular canals. 

CONGENITAL DEFECTS 

The defects in formation of the ear are of little pathological impor- 
tance, aside from absence or atresia of the meatus, absence of the exter- 
nal tympanic membrane or Eustachian tube, and hypoplasia of the 
functional structures like the ossicles and internal ear. Whole sections 
are sometimes missing. 

THE EXTERNAL EAR 

Hyperemia and hemorrhage are of slight importance, and are due to 

inflammation or injury. 

Hematoma auris occurs as a diffuse hemorrhagic extravasation be- 
tween the cartilage and its covering, and is due to trauma or certain 
dyscrasias. It occurs frequently in the insane, commonly on the left 
side, a fact which suggests that trauma may be its cause. Fibrosis, or 
degeneration of the cartilage, may result. 

Deposits of uratic or calcium salts are sometimes seen in the car- 
tilage or its covering. Within the auditory canal one frequently sees 
collections of cerumen and desquamated epithelium, even to the extent 
of forming hard tenacious masses. This is of little importance unless 
of long standing, under which conditions the skin may show dermatitic 
changes, and that portion over the drum may become eroded. Foreign 
bodies are frequently found in the external auditory canal. They 
may cause inflammation, but are more important because of the reflex 
nervous phenomena they occasion. Flies may lay their eggs and maggots 
grow within the canal. 

Inflammations. — Perichondritis is an exudative process in which 
the perichondrium is lifted from the cartilage. It may be localized or 
diffuse. Degenerations of the cartilage may ensue. 

Purulent auriculitis may follow the last, but is more apt to assume 
the form of boil or abscess, beginning in a sweat or sebaceous gland. 

The more diffuse non-purulent inflammations of the outer ear usually 
assume the form of a dermatitis of the canal, which may be of simple 
infiltrative or pseudomembranous nature. During and following 
influenza there is observed at times a bullous inflammation, assuming 
a serous or hemorrhagic form, in the osseous sector of the external 
canal involving usually the skin but occasionally stretching [ to the 
drum head. Suppurative processes do occur, but usually after trauma. 

Frost-bite of the auricle presents an edematous or bloody swelling 
which may proceed to ulceration or gangrene. 

Tuberculosis occurs as nodular fibrous tubercles without tendency to 
coalesce, but they do ulcerate late in the disease. 



THE EAR 



1035 



Syphilis occurs as primary lesions, secondary ulcerations in the 
canal, or gummata. 

Mycosis. — Moulds of the genera Aspergillus, Mucor, Oldium, and 
others grow in the external canal when moisture and a mild dermatitis 
make favorable soil for their development. The growth may be super- 
ficial, or may penetrate the skin or even to the middle ear. 

THE TYMPANIC MEMBRANE 

Hemorrhage occurs through traumatism, or spontaneously in 
certain general infections, or in hemophilia, scurvy, and purpura. 

Atrophy is the result of long-continued irritation by cerumen, 
concretions, inflammation, or by increased intra-aural tension by morbid 
collections. The whole membrane or only its fibrous layer is affected. 




Fig. 497. — Normal drum membrane 
as viewed through a speculum by 
reflected light (Barnhill and Wales). 



Fig. 498. — Bulging drum-head with 
beginning necrosis at the point of 
greatest pressure (Barnhill and Wales) . 



Rupture occurs by direct or indirect injury. Those due to indirect 
force, blows, explosions, etc., are usually in the anterior or superior 
parts. The drum may be perforated from within outward by inflam- 
mation in the tympanum, or by pressure necrosis; in the first case the 
membrane itself may be involved. Healing is accomplished by cica- 
trization, in which the fibrous layer may not be replaced and in which 
calcification not infrequently appears. 

Inflammation. — Acute inflammation is either an infiltrative or 
catarrhal condition. The membrane is swollen, opaque, and may show 
small dots of greater accumulation of the exudate. It is due to ex- 
tension from other inflammations or direct injury. 

Chronic inflammation is secondary to acute, or to prolonged or 
repeated otitis media. There is diffuse or irregular fibrous thickening 
and nodular granulation tissue. 

Tuberculosis occurs'as miliary lesions or caseous masses. 

Syphilis takes the form of mucous patches or gummata. 

TUMORS OF THE EXTERNAL EAR 

Polypi are the commonest masses in this situation, and are usually 
due to overgrowth after inflammation. Various degenerations occur in 
them. Warts have been seen in the canal or on the drum-head. Ecchon- 
droses or exostoses grow from the perichondrium or periosteum, and may 
be sessile or pedunculated. A curious and not uncommon form is annu- 
lar; it often follows prolonged inflammation and is said to be due at 
times to too frequent cold bathing. 



1036 



A TEXT-BOOK OF PATHOLOGY 



True neoplasms of this area embrace fibroma, osteoma, chondroma, 
sarcoma, and carcinoma, the last being basal cell in type when from 
the auricle and usually glandular when arising within the canal; large 
fungoid ulcerating masses of epithelioma sometimes grow from the 
pinna. Various angiomata are known. 

Upon the inner surface of the tympanic membrane cholesteatoma 
has been found. 

Sebaceous and dermoid cysts occur along the canal. 

THE MIDDLE EAR 

Hemorrhage is due to acute inflammation, trauma, caries of bone in- 
volving vascular channels, and it may occur spontaneously in nephritis. 

Passive hyperemia occurs in heart and lung disease, from pressure 
upon the jugular vein, or when the air is absorbed from the cavity after 
closure of the Eustachian canal. 




Desquamated epithelium 

Fig. 499. — Section of drum membrane; case of chronic otitis media suppurativa (prepared 
by Dr. H. C. Low) (Barnhill and Wales). 

Inflammation, or Otitis Media. — This disease process appears in 
acute and chronic types, and assumes a catarrhal, purulent, or fibrosing 
form. The etiology must^ consider the three ways in which the tym- 
panum j can be infected. Extension from the pharynx and retro- 
pharyngeal tissue occurs through the Eustachian tube from various 
inflammatory foci. Bacteria may be forced up the canal by douch- 
ing or sneezing. Adenoids favor the collection of microbes near the 
tube openings in the pharynx (see Eustachian Tube). The cavity may 
be infected through the tympanum by injury or extension, while in the[in- 
fectious diseases otitis media may be caused by germs brought in the 
blood-stream. Staphylococci, streptococci, and pneumococci are the 
commonest pus formers, but a single kind of organism is seldom present. 

Catarrhal otitis media, in its acute form, produces a reddened, swollen, 
and infiltrated mucosa, and a turbid mucous exudate. The drum 



THE EAR 



1037 



is congested and bulges. In the chronic form, either as a successor 
of the acute, or arising as a result of repeated irritations in rheumatic 
and gouty subjects, the mucosa is irregularly thickened and may show 
exuberant fibrous and epithelial granulations. The drum-head is prac- 
tically always stiffened and the ossicles limited in their movements. 

Purulent Otitis Media. — The acute purulent variety is commonly 
secondary to the catarrhal and there is really no sharp line between 
the two. The exudate becomes purulent, the infiltrate involves the 
drum-head, which softens and may slough, and the ossicles loosen or 
may be necrosed in the severe cases. Extension may take place through 
the petrososquamosal suture, along the lymphatics or small veins of 
the skull, or by ulcerative osteitis directly through the bone to the 
meninges or blood sinuses when the mucosa is ulcerated, or it may 
burrow to the external surface. The mastoid cells are always somewhat 
involved in otitis media, the lesion being a mucocatarrhal or suppurative 
process upon which membranous or osseous ulceration may supervene. 
In the last case the pus, unless relieved surgically, burrows externally, 
or internally to the lateral sinus and meninges ; septicemia nearly always 
accompanies this state of affairs. 

Chronic purulent middle-ear inflammation is a sequel of repeated 
acute attacks. The mucosa is considerably thickened by round and 
polynu clear cell infiltration and subepithelial granulation tissue. The 
cavity is filled with pus and blood, which, when the drainage is poor, 
may become inspissated. The tympanic membrane is practically 
always perforated and over its granulated edges, epithelium from the 
canal attempts to grow into the middle ear apparently in an effort to 
heal the defect. The lining of the cavity is irregular, being here polypoid 
from exuberant granulations covered with epithelium, there showing 
spongy hemorrhagic granulation tissue, at still another place presenting 
ulcerated mucosa or exposed bone. Sequestra may separate, con- 
sisting of ossicles or pieces of the wall, their presence helping to keep 
up the nflammation. In the drier cases warty excrescences may form or 
collections of epithelia and necrotic debris may produce a cholesteotoma. 
The bony casement of the tympanum is attacked by necrosis which 
may penetrate into the inner ear with extensive disintegration of the 
whole labyrinth. The ossicles are at first loosened, then become necrotic. 
The penultimate stage is an enlargement due to the necrosis, while the 
last phase is one of total necrosis and extension to the mastoid cells, 
blood sinuses, or meninges in the unfavorable cases, and fibrosis with 
bony overgrowth, middle-ear exostoses, in the more favorable ones. The 
cavity decreases in size in the last instance. 

In addition to the above chronic otitides there are varieties of fibrotic 
change of the soft parts within the tympanum which may be classed 
as inflammations because they are progressive, although unattended 
with much swelling, congestion, or infiltration. These changes may 
follow acute inflammation, but may also arise insidiously. One form 
is the polypoid proliferative variety, in which the fungoid masses are 
covered with cylindrical or ciliated epithelium. Adhesive otitis is due 
to the bridging of the cavity by bands of hyperplastic fibrous tissue . 
The bands sometimes cut off sections of the cavity, in which fluid collects, 



1038 



A TEXT-BOOK OF PATHOLOGY 



the cystic variety. Sclerotic otitis is an atrophic variety with interstitial 
induration, stiffening or ankylosis of the bone chain, periostitis, or 
exostosis in cases of long duration. 

Tuberculosis of the tympanum takes the form of an infiltrative 
ulcerative caseous lesion which follows the pathological course outlined 
for chronic purulent otitis media. It is always secondary. 

Syphilis appears in the tympanum as an acute or chronic inflam- 
mation in the secondary or teritary stages. 

Tumors. — Polypi, the result of inflammation, are the commonest 
new growths. They may attain considerable size and protrude exter- 
nally. They are covered with epithelium which may show any form of 
metaplasia. Histologically, such masses present angiomatous, myxo- 
matous, fibromatous, or adenomatous characters. 

Malignant new growths are uncommon, but sarcoma and carci- 
noma are the most frequent. 

Cholesteatoma. — In some cases of chronic purulent otitis media 
there arises a mass made up of squamous epithelium and cheesy mat- 
ter. It is probably the result of metaplasia of the normal columnar 
epithelium into flat cells, which assume a lamellated arrangement. 
This so-called cholesteatoma is looked upon by most pathologists as 
due to prolonged irritation and not as a neoplasm. 

THE EUSTACHIAN TUBE 

Inflammation, usually the catarrhal type, is rarely primary, but 
originates as an extension process from the middle ear or the pharynx. 
The tube is closed by swelling of its wall and the collection of exudate, 
thus preventing the passage of air from the pharynx, so that decreased 
pressure exists in the tympanum from absorption of the air therein. 
Continued or recurrent inflammations lead to stenosis of the tube, 
damage to the ear, and deafness. 

Obstruction of the Eustachian tube also results from hypertrophic 
mucous membrane about its opening in the pharynx, or by negative 
pressure when the nasopharynx is' obstructed by adenoids. This de- 
creased pressure draws the mucosa of the tube downward and collapses 
the lumen at the same time. 

THE INTERNAL EAR 

Circulatory disturbances of this part of the ear are similar to 
those given for the tympanum. Hemorrhage is, however, more serious, 
as it almost always leads to nerve-fiber degeneration, even though 
quickly absorbed. 

In acute infections, leukemia, and pernicious anemia the hemor- 
rhages are small, while in trauma they may be rapidly spreading and 
destructive. Hemorrhagic extravasation occurs in Meniere's disease, 
partly, however, of inflammatory origin. 

Inflammations in the internal ear are secondary to disease in the 
middle ear or cranium by extension, or to conditions elsewhere, the blood 
then bringing the bacteria. The processes are usually acute and follow 
the pathological changes given for the tympanum, except that to these 



THE EAR 



1039 



features must be added alteration of the special sense organs, which 
easily undergo degeneration and are probably never replaced. Caries 
and necrosis of the bone frequently occur. When the process is more 
fibrous one thinks of its probable syphilitic origin. The suppuration 
in the internal ear spreads to the tympanum or to the skull, to the 
latter traversing the internal auditory canal along the sheath of the 
auditory nerve. This is also the course followed in reverse, when menin- 
gitic inflammation invades the middle and internal ear. 



CHAPTER XVII 



THE SKIN 
ANATOMY 

The skin consists of two layers: the epidermis, composed of stratified 
epithelium; and the cutis, a layer divided into corium, or true skin, and 
the supporting connective tissue below. Some epithelial structures, 
hair-follicles, sebaceous and sweat-glands, lie in the cutis and subcu- 
taneous tissues. The epidermis consists from without inward of a horny 
layer of flat translucent cells beneath which is a clear layer of shining 
cells containing an albuminous substance, eleidin. The next deeper 
layer is composed of the granular cells of the rete Malpighii, in which 
lie granules of keratohyalin. Below this are the polygonal cells of 
the prickle-cell layer lying upon the deepest, or basal cells; these last 
are ovoid or short cylindrical epithelia. In all the layers of the rete 
protoplasmic bridges pass from one cell to another. The basal epithe- 
lium is the youngest and grows outward to form the upper rows. It 
rests upon a hyalin basement-membrane, separating the epidermis 
from the corium. The corium is divided into the papillary and reticular 
layers. The epithelium follows the curves made by the papillae of the 
upper layer. The stalk of the papillae is made up of delicate elastic and 
collagen fibers and blood-vessels, while deeper down the connective 
tissue runs in stout bundles. The subcutis is a looser adipose and 
connective-tissue layer of quite irregular thickness. 

Hair-follicles lie in the corium or subcutis surrounded by a thick 
fibrous mantle, within which is a hyalin basement-membrane carrying 
cuboidal epithelium. In the epidermis and to the openings of the 
sebaceous glands, all layers of epithelium follow the line of the hair- 
follicle. Sebaceous glands open upon the hair-follicle in the malpighian 
layer. These glands are racemose in form and the cells correspond to 
the deep epidermal cells. At the base of the hair-follicle is a papilla of 
connective tissue upon which rests the group of epithelial cells which 
form the matrix of the hair. 

The sweat-glands are long tubular structures with a coiled internal 
extremity and a spiral passage through the epidermis. 

The blood- and lymph-vessels of the true skin are very numerous 
and anastomose freely. The nails are stratified layers of horny epi- 
thelium arising in a bed made of large papillae and a wide basal epi- 
thelial layer. The pigment of the skin lies in the deep layers of the 
rete of the epidermis and in the corium. It is iron-free melanin, and 
made by chromatophores in the corium. 

It is impossible, within the space allotted to the subject in this book, 
to give more than the general characters of diseases of the skin. The 

1040 



THE SKIN 



1041 



subject has been greatly studied, but microscopical examination reveals 
much less than the clinical observation would warrant one to expect. 
The skin is in close relationship with some of the internal organs, and is 
so extensive and in such an exposed position that its lesions are numer- 
ous and varied. They are here considered from the standpoint of 
general pathology, with little reference to the clinical manifestations. 

CONGENITAL ABNORMALITIES 

Nevus is the most important congenital defect, although not the 
only one, since whole sections of skin surface may be missing. Nevi 
appear in the following forms: 

Simple angiomatous telangiectasis, wine stain, a flat or slightly raised 
red or purple stationary growth. 

Cavernous angioma, a cystic angioma of blue color. 

Pigmented nevi consist of angiomatous, fibrous, and epithelial hy- 
perplasia, carrying pigment both in epithelial and cuticular layers. 
They may be flat or raised, minute or very extensive, smooth, hairy, 
or uneven. Microscopically, one finds masses or columns of large some- 
times multinucleated cells lying in the corium, about and within which 
pigment may be found. There has been much debate about the identity 
of these elements but perhaps most weight lies with the argument that 
they are epithelia derived from the basal layer of the rete; they have 
no protoplasmic bridges. These nsevi are important because sometimes 
they become rapidly malignant in growth and metastasize. 

' Sebaceous nevi are flat or slightly raised yellow areas, commonly 
on hairy parts, the result of increase in the sebaceous glands. 

Atypical epithelial growths of basal or glandular cells, congenital 
in origin, sometimes form raised cystic or solid benign epithelioma ade- 
noides. Lymphangiomata of congenital origin sometimes occur in 
the skin. 

ATROPHY, HYPERTROPHY, AND DEGENERATIONS 

Atrophy of the skin occurs as primary atrophic dermatitis, in 
senility, as the result of lowered nutrition as in neuritis, after prolonged 
undue stretching, and, secondarily, in constitutional diseases like diabetes 
or tuberculosis. The epithelial layer becomes thin, the lower cells are 
irregularly pigmented, the papillae are flattened, the hair-follicles short- 
ened, the hairs become wooly or cease to form, the sebaceous glands dis- 
tend and empty their secretion into the hair-follicles so that both cavities 
distend to a cyst or wen. The collagen or even the elastic fibers of the 
corium undergo hyalin or granular degeneration. Sweat-glands are 
usually well preserved. 

Hypertrophy of the skin may affect either layer or both, but in 
any case one layer has more prominent changes than the other. In 
hypertrophy of the epidermis there is a condition termed hyperkera- 
tosis in which there is reduced desquamation of the horny layer, the 
cells adhering closely to one another, and the whole layer is firmly ap- 
plied to the rete, the cells of which may show active proliferation. The 
commonest epidermal hypertrophy is the callosity, due to pressure 
or rubbing, in which the granular layer of epithelium increases and 

66 



1042 



A TEXT-BOOK OF PATHOLOGY 



assumes a dense homogeneous yellow appearance. On the other hand, 
the rete cells may be pressed down, distort the papillae and upon them 
collect into softened masses, or corns. Cutaneous horns, not infre- 
quently of congenital origin, are due to hyperkeratosis together with 
downgrowth of the basal epithelium, so called acanthosis, into the corium, 
the papillary layer of which is distorted and may show branching. 

A large number of clinical forms of keratosis are recognized by der- 
matologists but they seem to have a closely similar histological basis. 
The essential feature of all is the destruction of the normal proportions 
of the various epidermal layers, the horny and basal divisions being 
excessive. In nearly all varieties there seems a tendency toward malig- 
nant new growths. Within the corium, low grade inflammatory reaction 
exists, indicated by excessive mast and plasma cells. The glands seem 
involved to the extent that their excretory ducts are obstructed by, or 
included in, the hyperkeratosis or acanthosis. 

Ichthyosis is a congenital or acquired condition characterized by 
the occurrence of large plates of horny epithelial crust or scales. Under 
the microscope one finds great widening of the horny layer with plugs of 
homogeneous epithelial cells filling the outer part of the hair-follicles. 
There is often excess of pigment in the epithelium lying upon the corium, 
but the granular epithelial layers may be missing. Not infrequently 
perivascular infiltrations and a mild fibrous thickening exist in the 
corium, which in congenital or long-standing cases leads to atrophy. 
In congenital ichthyosis the body is covered with dry folded or scaly 
skin, traversed by deep fissures, giving the appearance of crocodile skin. 
In the acquired form the skin is dry, shining, pigmented, and covered 
with friable crusts or scales separated by cracks. 

Warts, or verrucae, are composed of hyperplasias of horny and prickle 
cells with a slight increase in the corium, while in condylomata there are 
thickenings of both layers. Perhaps the most pronounced part in these 
formations is taken by the papillary layer, which may grow out like long 
villi, the surface being covered with very much thickened epithelium. 
The process is both a hyperplasia and hypertrophy, principally of the rete 
mucosum and of the papillary layer of the cutis. The connective tissue 
in both these growths is very rich in blood-vessels. Some leukocytic 
infiltration appears. Both these hypertrophies are said to be contagious, 
and this surely seems true of the condylomata, as they are frequently 
associated with venereal disease and appear most often around the 
genitals. 

The pathology of those conditions affecting the outer layer, or both, 
having been discussed, it remains to consider the hypertrophies most 
prominent in the corium. The principal features are increase in the 
elements natural to the membrane, but to this is added fibrotic changes 
which naturally follow increase of blood, or succeed upon continued 
irritation. 

Scleroderma is a diffuse or disseminated hypertrophy of the skin 
of unknown cause, but thought to be associated with nervous or thyroid 
disease. The skin is hard, firm, and stretched. Under the microscope 
one finds increase of connective tissue arranged in bands. The skin 
muscles, and subcutaneous tissues are involved. The blood-vessels 



THE SKIN 1043 

show chronic thickening of all their walls, including obliterating end- 
arteritis. Atrophy soon arrives and leaves a dry, lifeless surface. The 
epidermis does not suffer. In the congenital forms, called sclerema, these 
lesions are associated with edema, while in the fatty form the corium 
has a yellow fatty appearance which may or may not be due to true fat. 

Elephantiasis is a chronic thickening of the corium and deeper tissues 
of unknown origin in some cases, while others are due to filaria in the 
lymph-vessels (tropical form), to passive congestion, chronic dermatitides, 
like eczema, and to mechanical lymph and blood stasis. The skin is 
greatly increased in its whole depth, stiff, and cannot be folded, which 
pachydermatous condition gives the disease its name. Marked dis- 
figuration of legs or other parts is common. The disease is especially 
common in the scrotum. Connective tissue increase from the epiderm 
to the muscles is found by histological study. Elastic fibers are decreased 
in number. The vessels are fibrosed and thrombotic. Glandular struc- 
tures soon atrophy. 

Necrosis of the skin may be due to injury, or disease'of nerves or the 
spinal cord, and is exemplified in pressure sores (decubitus). There is 
at first redness and swelling, followed shortly by dense infiltration and 
dry hardness of the part. Shortly, blisters or blebs form, and the deeper 
tissues degenerate. An ulcer soon appears with swollen reddened edges, 
a slough is cast off, and healing occurs by scar formation. The latter 
part of the process may be considered as gangrene. Gangrene of the 
severer grades, aside from the cases arising from nervous diseases, may 
follow injury, such as freezing and burning, especially where blood-supply 
is cut off and cannot be established by collateral means. In diabetes 
and ergotism the cause is not clear. In these cases multiple areas of 
gangrene are common. Senile gangrene of the foot begins in the skin. 
Some gangrenes, like noma, result from the introduction of masses of 
bacteria, mostly anaerobic, through wounds. 

Symmetrical gangrene of Raynaud is multiple and appears upon 
corresponding parts of both sides of the body (fingers, ears). It is 
probably due to combined nerve and vascular defect. Perforating 
ulcer of the foot is a form of local gangrene depending upon neuro- 
trophic disturbances. 

Regeneration of the superficial skin takes place perfectly when the 
defect has not been deeper than the papillary layer. The rete, from the 
edges of the defect, grows together until it covers the surface. If, 
however, the corium has been damaged, scar tissue results, and the 
defect is replaced by a fibrous tissue poor in vessels and cells. The elastic 
tissue may be imperfectly replaced, but the glandular structures are 
missing. If the fibrous tissue be excessive, a prominent hypertrophic 
scar remains. Atrophic skin is replaced by scar tissue, but traces of 
the essential tegument ary structures remain. 

VARIATIONS IN PIGMENTATIONS 

Increase of the pigment affecting a large part of the body occurs in 
Addison's disease and upon exposed parts after exposure to the sun. 
Local increase of pigment is found in freckles, in chloasma or "liver 
spots." Presence of abnormal pigmentation is seen in jaundice and 



1044 



A TEXT-BOOK OF PATHOLOGY 



certain poisonings like that from silver. Increase of pigment may be 
seen after the absorption of hemorrhagic extravasations, the coloring 
matter being then hemosiderin. In cases not due to hemorrhage, to 
foreign chemicals or to jaundice, it is probable that the variations of 
pigmentation depend upon the amount and manner in which melanin is 
laid down, for it does not seem that new coloring matter is deposited in 
places or cells not customarily containing it. 

Decrease of the general pigment is exemplified by albinism. Local 
decrease is seen in vitiligo and in scars. 

CIRCULATORY DISTURBANCES 

Anemia may be general or local. The former is seen in anemia, 
hemorrhage, and shock. Local anemias are due to cold, vasomotor 
neuroses like Raynaud's disease, or obstruction to the circulation. 

Hyperemia. — Active hyperemia is the result of irritation, excessive 
warmth or cold, or of internal vasomotor conditions due to toxic or 
infectious causes. Small local hyperemias are called roseola; general 
reddening is erythema. 




Fig. 500. — Urticaria — section of a wheal: e, Epidermis, practically no alteration; c, 
corium, showing acute inflammatory changes, swollen and infiltrated with serous exuda- 
tion, with the blood-vessels (v, v, v), especially those accompanying the sweat-ducts (s, 
s, s, s), dilated and surrounded by and containing numerous polynu clear leukocytes; 
lymphatic vessels (I, I) and spaces also enlarged, containing granular matter; numerous 
mast-cells {m, m) scattered through the corium (courtesy of Dr. T. C. Gilchrist). 



Passive hyperemia, cyanosis, or blue skin, may be general in cases 
of venous obstruction near the heart, and in circulatory disease due 
to heart and lung disorders. It is then most marked in the extremities 
and face. Prolonged pressure hyperemia may lead to edema, or to des- 
quamative, sclerosing, or atrophic dermatitis. 

Hemorrhage into- the skin takes the form of petechia, ecchymoses, 
vibices (linear), and hematoma. It may occur in the corium 'alone 
or find its way to the epidermis. Its characteristic is that it produces a 
dark red or purple stain that cannot be pressed away. Hemorrhage is 
met with after some injuries, in infectious diseases, and in the various 
purpuras. 



THE SKIN 



1045 



Edema of the skin is the doughy condition arising when the venous 
circulation is cut off, the lymph flow obstructed, or the vessel wall and 
tissue tension changed, as in nephritis. It occurs also in what is called 
neuropathic, angioneurotic, or toxic edema (Quincke's edema) , the cause of 
which is not known. Urticaria is a local edema due to irritation or as a 
part of the last-mentioned group, and takes the form of circumscribed 
cellular edema of the corium, showing upon the surface as firm, flat, pale 
elevations with a pink margin (hives, dermatographia). These lesions, 
with hyperemia and erythema multiform, comprise a group of skin erup- 
tions often seen as indicators of certain susceptibilities (see anaphylaxis), 
and internists have lately sought to explain some of them as expressions 
of disturbed function on the part of the ductless glands. Edema may 
also occur within the epithelial cells causing them to be vacuolated or, 
when extensive, to consist of a large clear area with the nucleus pushed to 
one side, so-called " balloon cells." This dropsy is seen under many 
conditions but especially in eczema. 

INFLAMMATION (DERMATITIS) 

The inflammations of the skin are exudative in character for the 
most part, but are accompanied by certain hyperplastic, degenerative, 
and desquamative processes in the epidermis which lend to them at 
times a catarrhal appearance. Changes in one layer without concom- 
itant alterations in the other are rare. Following the plan noted in an 
earlier paragraph, there will be given here the pathological manifesta- 
tions in the various layers without dwelling long upon the clinical ap- 
pearances, the most important objective factor in the study of dis- 
eases of the skin at the present day. 

The causes of dermatitis are numerous and varied. They embrace 
injuries of various kinds by heat or cold; chemical and mechanical 
agents; intoxications by exogenous or endogenous substances; infective 
vegetable and animal organisms, and they may be the result of altered 
nutrition from faulty innervation or blood-supply. The cause of many 
dermatitides has not been discovered. 

The evidences of inflammation of the skin fall into certain fairly 
well-defined classes, and it is perhaps well that the reader be familiar 
with the terms given to the eruptions and their pathological meaning. 

Erythema is diffuse reddening of the skin with or without swelling, 
and subject to great variations. 

Macules are non-elevated, clearly outlined areas, presenting any 
color known to the skin. The size is usually small. 

Papules are elevated areas of various shapes, usually small and 
with clear margins. A mixture of these last two is known as a maculo- 
papule. 

Tubercles are sharply outlined firm swellings larger than papules, 
and sometimes warty in appearance. 

Vesicles are localized collections of clear fluid, the size of macules or 
papules, within the epidermis or between it and the corium. 

Bullae, or blebs, are large vesicles arising by separation of large 
areas of epidermis from its base by fluid, or by coalescing of vesicles. 



1046 



A TEXT-BOOK OF PATHOLOGY 



Pustules are vesicles containing pus. If very large, they are called 
ecthyma. 

Crusts are masses of dried exudate and epithelium. 
Scales are sheets of dead epithelium. 

The simplest inflammations of the skin, such as are found in scar- 
latina, in food-poisoning, or in idiopathic erythema, take the form of 
congestions of the corium, with varying grades of transudate or even 
cellular exudation. This may be confined to the corium and epidermis, 
but in the more severe grades, as scarlatina, it penetrates to the sub- 
cutis. These conditions are for the most part devoid of exudate upon 
the skin surface, but are followed at times by scale formation. The rete 
malpighii shows some swelling of the cells and a very slight intercellular 
edema. The inflammation may be diffuse, as in measles or food-poison- 
ing, or localized, as in erythema nodosum. 




Fig. 501. — Pemphigus — a beginning bleb (a) between corium and the epidermis, the 
bared papillae (6) forming the base; acute inflammatory- changes in the papillary layer of 
the corium, with marked serous exudation, particularly about the vessels; reticular part 
of the corium and the sweat-glands (s, s 3 , S4, s 5 ) are practically normal, except where the 
sweat-ducts (si, s*) are involved in the bleb-formation: d, corneous layer; e, rete; v, v, 
blood-vessels; c, cell masses at base; /, about the natural size of bleb examined (courtesy 
of A Dr. T. Caspar Gilchrist). 

The next higher grade of inflammation is indicated by more intense 
edematous and cellular infiltration of the upper layers of the corium, 
with penetration of the fluid to the malpighian epidermal layer. The 
fluid pushes aside the cells of the basal and prickle cell layers, where it 
may form vesicles, being held in place by the horny layer through which 
the fluid cannot pass. The deep epithelium becomes necrotic and softens, 
a process which may be due to the actual cause of the dermatitis in 
some cases, and is, therefore, primary. The vesicles may dry and cover 
themselves with a crust, or break and leave a weeping surface. The his- 
tological changes in the corium are cellular, edematous swelling of the 



THE SKIN 



1047 



papillary layer, congestion, and perivascular collections of round cells. 
For examples of this process one can turn at first to herpes in any of its 
various forms. This condition presents patches of small vesicles tightly 
filled with clear or slightly cloudy fluid, surrounded by an areola of 
swollen injected skin. The vesicles are situated in the deep layers of the 
rete. The cause of herpes is not known, but the disease is thought to be 
due to nerve irritation or an infectious agent. A more extensive vesicular 
process is found in pemphigus. Here one finds large bullae upon normal 
or slightly swollen bases, with clear or slightly cloudy contents. The 
cysts arise by exudation between the corium and the epidermis, although 
at times some epithelium is seen lying upon the papillae. The blebs 
become purulent, burst, or dry and form crusts. The cause of the 
various forms of pemphigus is not known, but it frequently appears upon 
syphilitic newborn children. 

Frankly infectious forms of vesicular dermatitis are varicella, variola, 
and impetigo. The first and the last form their vesicles fairly high in 
the epithelial layer, while the variola virus causes an early degenera- 
tion of the basal cells of the rete malpighii, to which suppuration is 
soon added. Impetigo is a disease due to some pyogenic organism; 
the vesicles are always purulent, and leave crusts upon a granulating 
surface. In all these conditions there is a frank exudative process in the 
corium, composed of polynuclears when pus producers are active and of 
round and plasma in the less infective varieties. 

Severe insults to the skin, like burning, freezing, and concentration of 
light rays, produce an exudative dermatitis with fluid collections in the 
epidermis. This result is due both to exudation and damage to the 
epithelium itself. The vesicles, or blebs, are filled with serum, which 
may escape by rupture of the horny layer, thus leaving a weeping 
surface. In the severer burns this stage is short, a slough forming very 
early. In freezing, the same lesions may appear, but gangrene is more 
apt to occur. 

Eczema.' — This affection of the skin with its protean manifestations 
belongs in the exudative class because, with the exceptions of the very 
destructive or very old cases, the lesions, under the microscope, are 
essentially the same as in the immediately preceding groups. Clinically, 
the disease has innumerable modifications, but it commonly begins as 
an erythematous or vesicular dermatitis. The infiltration and swelling 
of the papillary layer are marked, especially about the enlarged blood- 
vessels and lymph-channels. Vesicles occur in the usual manner by 
destruction of the deeper epithelium by pressure, but even if distinct 
collections have not occurred there still is an excess of fluid present 
in the epidermis. This fluid finally finds its way to the surface and the 
superficial cells are removed in crusts. To replace the lost surface cells 
the deeper layers actively push out and new superficial layers are formed 
which retain their nuclei but do not contain the normal keratin (parakera- 
tosis). This leaves a surface covered with cells of the malpighian layer, a 
softer, pinker, more sensitive, and probably weeping area. The deeper 
layers may show acanthosis especially in the protracted cases, and it 
is common to find intracellular edema. In chronic cases, however, 
especially of the dry varieties, there is a hyperkeratosis, a condition in 



1048 



A TEXT-BOOK OF PATHOLOGY 




Fig. 502. — Eczema seborrhoicum, section of a small papule in the type commonly 
known as "seborrhcea corporis.'" A hyperplastic horny layer and dense inflammatory 
cell-infiltration in more or less of the entire corium, with slight edema (courtesy of Dr. 
Geo. T. Elliot). 




Fig. 503. — Eczema — sluggish, deep-seated, vesicular type, with scattered lesions and 
somewhat thickened corneous layer, commonly seen on the fingers; section from palmar 
surface of a finger (low magnification) : a, a, Represents a vesicle in the earliest observable 
stage; the mucous layer in the lighter part shows molecular changes, and corresponds to 
the area of "inflammation in the papillary layer of the corium below. The papillae show 
marked serous exudation, dilated blood-vessels, and invasion of leukocytes (courtesy of 
Dr. A. R. Robinson). 



THE SKIN 



1049 



which the excessively produced epithelial cells are not desquamated, 
but remain as crusts or scales. The papillae are variously altered also 
by fibrosis in chronic cases. The cause of eczema is unknown. It 
has been ascribed to infection and endogenous or exogenous intoxication; 
in certain cases it has been thought to be an expression of susceptibility 
to certain food stuffs. 

The consideration given to the imperfect formation of the horny 
epithelium in eczema leads to a discussion of those inflammations in 




Fig. 504. — Psoriasis (recent papule). Note increased thickness of the horny layer 
of the epidermis and its arrangement in lamellae with retention of nuclei in the lower 
layers. The rete mucosum is widened and there is a moderate exudate of lymphoid cells 
in the papillae of the corium most noticeable at left of section. (Hartzell "Diseases of 
The Skin"). 

which, by reason of faulty nourishment of the epithelium from the 
corium or functional disarrangement of the deeper layer of the epidermis, 
an abnormal or excessive production of horny epithelium (para- or 
hyperkeratosis) takes place and expresses itself in cast-off scales of various 
dimensions. In those conditions where the frank inflammatory lesions 
recede, less fluid passes through the rete malpighii, but, nevertheless, 
some degree of acanthosis is always present. This may be simple compact 
hyperplasia or a separation and degeneration of some of the cells, and 



1050 



A TEXT-BOOK OF PATHOLOGY 



irregular hyperplasia to make up for the cast-off superficial layers. 
Irregular horny layers are produced and cast off because of the lesions 
below, which consist of fibrous changes of the papillary layer, or even 
deeper. In this class fall psoriasis and lupus erythmatosus. In psoriasis 
the horny layer is increased in thickness, and the cells separated by 
leukocytes, organisms, and air, to the last of which the silvery sheen of 
the crusts is ascribed. The rete cells are separated and hyperplastic and 
fluid lies between them. Keratohyalin is lacking. Distinct thickening 
occurs in the corium and the papillae are irregular. 

To this exfoliative class belongs also pityriasis rubra, a condition in 
which the corium changes are equal in importance to the epithelial, and 
which goes on to atrophy. 

In lupus erythematosus the corium shows at first vascular dilatation, 
then obliterative endangitis with marked plasma cell and lympho- 
cytic infiltration about the vessels and sebaceous glands; the last are 
hyperplastic and filled with secretion. A hyaline deneration occurs in 
the collagen and elastic tissue, connective tissue cells decline in numbers, 
and atrophic cicatrization results. Moderate hyperkeratosis occurs while 
the basal layer of the rete is slightly active at first, but later becomes 
atrophic. 

Papular eruptions are known in many skin diseases. As would be 
expected, the chief seat of the swelling is in the corium, where a local- 
ized cell and fluid infiltrate occurs. To this may be added a hyperplasia 
of the epithelial layer, the cells of which are separated by fluid or leuko- 
cytes. True vesicle formation may occur on top of a papule. In other 
cases the papule may be caused by an increase in the rete epithelium 
alone, either on the free surface or at the openings of glands. Prurigo 
and lichen belong to this class of pathological changes in pure form, 
but it should be remembered that papules may occur in almost any 
dermatitis. 

Inflammation Chiefly Affecting Hair-follicles and Sebaceous Glands. — 
These two structures are usually involved together by reason of their 
close anatomical association. An obstruction to the outlet of the 
follicle dams back secretion, and bacteria, sinking in along the hair, 
easily invade the gland. Obstruction can take place when accu- 
mulations of epithelial cells and sebaceous material become dried 
about the hair. This may hold back the secretion until it becomes 
hardened into a comedone. If this retained secretion becomes infected 
by pus cocci, various lesions arise. In some, as sycosis, the hair-follicle 
and its surroundings show the most effect, while in acne of the simpler 
variety the disease is fairly well limited to the sebaceous gland. 

Acne vulgaris is an adenitis or folliculitis, expressed by small pus- 
tules and a mild concomitant dermatitis, due to bacterial infection, prob- 
ably with staphylococci and the Bacillus acne of Unna acting together. 
Some persons seem to have a special disposition to it, especially at 
puberty. It may occur after the use of bromids and iodids. Sycosis 
is the invasion of staphylococci into the perifollicular tissue so that a 
more definite dermatitis accompanies the folliculitis. The lesions while 
usually most pronounced high in the corium at first may penetrate to 
the depths of the glands and cutis. In both these diseases, if active 
suppuration occur healing is b} r scar tissue. 



THE SKIN 1051 




Fig. 505. — Lichen planus — section from a chronic patch (moderately high magnifica- 
tion) : a, b, c, Show respectively the corneous layer, granular layer, and rete — all consider- 
ably thickened; e, e, microscopical cavities, with serous exudate; d, corium, infiltrated with 
exuded round cells, and with marked increase in the size of the connective-tissue corpuscles 
(courtesy of Dr. A. R. Robinson). 




Fig. 506. — Acne rosacea: a, Enlarged sebaceous glands; b, their distended ducts; c, in- 
creased vascularization (Aschoff). 



1052 



A TEXT-BOOK OF PATHOLOGY 



Acne rosacea is a diffuse sclerosing dermatitis with increased seba- 
ceous secretion from hypertrophic glands which may or may not show 
inflammatory changes. It occurs commonly on the nose and. cheeks 
as a red, irregular, uneven, or nodular patch. Vessels are large and dis- 
tended; fibrous tissue is increased and may constrict the sebaceous 
gland ducts. 

Furuncle is a localized suppuration of the skin starting in a sebaceous 
gland, and characterized by the formation of a central necrotic slough 
and a densely infiltrated wall separating it from the healthy tissue: 
This wall is not sharply defined, but fades into healthy parts. The 
cavity, after evacuation, heals by granulation. Furuncles are due to 
the pus cocci penetrating the follicles, especially when favored by slight 
injury. 

Carbuncle is a compound furuncle formation characterized by soft 
necrotizing spread and multiple sloughing openings in the skin. This 
is due to staphylococci or streptococci. General lowered vitality favors 
the inflammation, and furuncles appear as skin complications in diabetes, 
marasmus, and the like. 




Fig. 507. — Vesicles on surface of pustule due to the anthrax bacillus (Mallory). 

Malignant pustule, or anthrax, is a localized suppurative and gan- 
grenous process. There occurs rather superficially a dark red or brown 
edematous and indurated swelling which soon softens in the center, 
but underneath there is a firm slough. The minute pictures show a 
purulent collection containing anthrax bacilli in the deeper epithelial 
layers, elevating the epidermis from the papillae. The inflammatory 
process in these last three conditions is one of fibrinous, purulent, and 
liquefactive character. 

Inflammations Chiefly Affecting the Corium and Subcutis. — Diffuse 
inflammations take the form of infiltrations, which range from simple 



THE SKIN 



1053 



edema with congestion to suppuration. They all tend to spread, 
but in so doing are preceded by a zone of congestion or dense infil- 
tration. The simplest of these processes is erysipelas, an acute 
or subacute infection due to streptococci. There is congestion and 
serous or serofibrinous infiltration of the corium with hydropic degenera- 
tion of the rete, often going on to vesicle formation. Cellulitis is next in 
severity, affecting chiefly the subcutaneous tissue, although the true skin 
is almost always infiltrated. In this lesion there is extensive fibrinous and 
cellular exudate. It is commonly the result of infection through the 
lymphatics. Phlegmon is the name given to a true suppuration in the 
corium and subcutis. It is a rapidly spreading purulent infiltration, 
which may break outward and discharge, or penetrate the muscles 
inward. 

Ulcers of the skin, be they infectious, like soft chancre, or due to 
metastasis through lymph-or blood-stream, begin by serous or sero- 
cellular infiltrate of the deeper epidermis with extension outward and 
laterally. Of course, whole sections may be discharged when phlegmon 
has isolated an island of skin by cutting off its nutrition. 

SPECIFIC INFLAMMATIONS 

Under this heading come the class of infectious granulomata and 
mycotic diseases. The etiology and histopathology of the former have 
already been discussed (see Chapter V), and it remains to be pointed out 
here how they appear in the skin. 

Tuberculosis of the skin, or lupus, may be primary or secondary, 
in the former case being directly inoculated into wounds. It occurs in 
many forms, as flat thickenings, as uneven, slightly raised areas, 
or as excrescences, or even verrucae. The tuberculous process as- 
sumes the diffuse fibrous form, with here and there giant cells, and 
an occasional fully formed miliary tubercle but epitheloid cells are scarce 
and true caseation very rarely exists. The seat of the lesion is the 
corium, the supporting fibers of which layer degenerate. There are 
numerous lymphocytes and mast cells about the infiltrate. The epi- 
dermis is little affected, except in the warty inoculation form, when 
it may be thickened in the horny layer. In some of the moist forms a 
parakeratosis is found and occasionally columns of basal cells may 
be seen extending in an irregular manner between the distorted papillae. 
Tubercle bacilli are difficult to discover in the lesions of lupus. General 
fibrosis of the lesion is a common method of healing, and scar tissue is 
extensive and disfiguring. The common form is known as lupus vulgaris, 
which appears usually upon the face. The primary inoculation, or 
warty form, is lupus verrucosa, seen oftenest upon pathologists, veteri- 
narians, and butchers. Two forms of ulcerative tuberculosis of the skin in 
early life are the miliary and scrofuloderma, the latter being common near 
caseous glands, and seeming to be an infiltration with fibrosis and atrophy 
due to the adjacent lesion. 

Syphilis. — The primary lesion, or chancre, occurs usually on the 
genitals, but may be implanted anywhere. It appears as a hard mass, 
occupying all layers of the skin, and shows a tendency to early ulcera- 
tion. The firmness is due to a dense infiltration and proliferation in the 



1054 



A TEXT-BOOK OF PATHOLOGY 



whole corium, being diffuse in the papillae, and close about the blood- 
and lymph-vessels lower down. Multiplication of connective-tissue 
cells soon appears. The Spirochaetas are found everywhere, but espe- 
cially near the vessels and in their walls. 

The secondary lesions may assume any form of eruption known to 
the skin. They have a tendency to be pigmented and polymorphous. 
Early in the disease the eruption is symmetrical, but later it is com- 
monly localized. Histologically, there is an infiltrate of small round 
cells in the papillary layer and increase of connective-tissue cells here 
and there deeper in the corium. Exudates of fluid character may appear 
either in the papillary layer or rete malpighii. 

Gumma, or the tertiary lesion, appears as a firm swelling, rather 
deep in the skin, which shows a tendency to soften and ulcerate outward. 
(See Histology of Gumma.) Spirochceta pallida are numerous in the 
secondary lesions, especially those giving a moist surface (condyloma 
latum), but they are found with difficulty in gummata. 

Yaws produces a dense infiltration of the corium with round and 
plasma cells, the epiderm showing a distinct tendency to acanthotic 
growth downward between hyperplastic papillae. The blood vessels 
are not involved as they are in syphilis, nor are there any giant cells. 

Leprosy. — The lesions of leprosy take place in the corium and 
subcutaneous tissue, and seem to have a predilection for nerves and their 
surroundings. They compress glandular structures. Connective tissue 
overgrowth is common in later stages. 

Actinomycosis and glanders occur in the skin by direct inocula- 
tion, or by extension. The process is one of necrotizing cellulitis sur- 
rounded by granulation. 

Mycosis fungoides has been described (see page 208). 

Mycoses of the skin are caused by moulds (hyphomycetes), which 
invade the epidermis and the structures arising therefrom, especially 
the hair-follicles. Some moulds enter the hair shaft, others surround 
the hair while still others remain in the follicle or deep epiderm, or may 
even invade the corium. Many biological varieties of these hyphomyces 
have been described but as their peculiarities are too intricate for a book 
of this sort, the reader is referred to works upon mycology and 
dermatology. Blastomycetes also produce a dermatitis, but penetrate 
to the corium or are brought thither by the blood or lymph. 

Favus is an inflammatory mould disease presenting yellow concave 
crusts, or scutula, which are made up of the mycelium of the moulds 
and epithelium. These are well fastened to the deep horny layer. 
The mould, Achorion schonleinii, may penetrate the hair shaft and hair- 
follicle. In the epidermis is found a leukocytic infiltration. 

Tinea, or ringworm, is a dermatomycosis due to members of the 
genus Trichophyton. 

Tinea tonsurans gives a dirty gray crust of mould and epithelium 
upon hairy parts. The hairs are broken by the growth of mould within 
and around the hair. The base of the eruption is round and consists 
of swollen, slightly indurated skin, which may or may not be inflamed. 

Tinea circinata is probably a result of the same infection as the last, 
but occurs in less hairy parts of the skin. It grows in a spreading circu- 



THE SKIN 



1055 



lar manner by the spread of moulds within the deep epidermal layers. 
A mild congestion of the corium occurs. 

Tinea sycosis, also of trichophyton nature, occurs over shaven 
beards, and is due to the growth of mould into the hair-follicle and 
sebaceous gland. It is acneiform in appearance. 

Tinea, or pityriasis versicolor, is a desquamative condition due to 
the presence of Microsporon furfur in the horny epithelium. There 
are yellowish, reddish, or brownish spots covered by scales. There is 
little inflammation. 

Erythrasma is a scaly eruption upon warm and moist parts. It 
is said to be due to the Microsporon minutissimum. 






Fig. 508. — Molluscum contagiosum: a, Lobular epidermal growth; b, molluscum bodies; 
c, detritus as contents of central spaces (Aschoff). 



Blastomycosis and the related coccidioidal granuloma (see page 
366) are specific inflammations of both the epidermal and dermal layers. 
The affections present a diffuse thickening of the skin, with warty and 
ulcerative eruptions similar to epithelioma and tuberculosis. Papules 
or pustules may form. The lesions in the epiderm are infiltration of 
polynuclears between the deep epithelial layers, the cells of which are 
swollen and separated, and hyperplasia with irregular prolongations 
into the corium. Abscesses form, in which may be found the round 
or elliptical yeasts. Prickle cells are prominent, a feature which, when 
combined with the miliary abscesses, is very characteristic. The horny 
layer is widened and irregular. In the corium are small abscesses con- 
taining the organisms, a diffuse granulation tissue with cells of the 
small lymphoid series, endothelium, and, occasionally, a giant cell. 

Dermatitis Due to Animal Organisms. — The most important form 
is scabies, the itch, due to the Acarus scabiei, an arthropod. The 



1056 



A TEXT-BOOK OF PATHOLOGY 



female burrows a track in the horny epithelium, where she lays her ■ 
eggs. These hatch out, and the young burrow further. The inflam- 
mation that follows is due more to scratching than to the parasites, 
which, however, have some irritative action. Pediculi (lice) and fleas 
bite the skin, and produce an irritation. The dermatitis that appears 
is due to scratching, and may in prolonged cases take the form of a 
weeping eczema. 

Epithelioma or molluscum contagiosum is a flat or slightly raised 
firm mass supplied with a central depression and opening, having a 
waxy or pearl-like color, commonly the size of a pea, and situated most 
often upon genitals and head. The condition is believed by most but 
not all observers to be correctly named, " contagiosum." It consists, 
under the microscope, of radially arranged hyperplasia of the rete mal- 
pighii, separated into lobes by fibrous projections of the corium, which 
layer is much distorted by this downgrowth. In the center is a mass of 
desquamated cells and detritus which can be pressed out of the gross 
lesions. The rete cells are degenerated and many contain the so-called 
" molluscum bodies." These are clear spaces situated near the nucleus, 
and may at times or by special stains show an amorphous chromatic mass. 
They are probably degenerative or may be included with the Chlamydoza. 

TUMORS 

Fibroma is the commonest benign tumor of the skin. It appears as 
single large, firm swellings, or as multiple soft growths, sometimes indi- 
vidually, at others in groups, which arise from the connective tissue of 
nerve-sheaths (neurofibroma). Keloid is another fibromatous tumor of 
the skin. 

Lipoma occurs as single large, lax masses, or as multiple small 
growths, which may be symmetrically distributed. Xanthoma is a 
tumor appearing as yellow plates or warty masses chiefly about the face. 
It lies in the corium, and consists of connective tissue surrounding 
groups of fat-like, refractile bodies (xanthoma bodies) and clusters of 
epitheloid and multinucleated cells, arranged usually near blood-vessels. 
This tumor occurs in diabetes and occasionally in icterus. 

Myoma sometimes occurs in the skin, as do osteoma and chondroma. 

Angioma has been considered under Nevi, but those tumors consist- 
ing of vessels, and proliferated lining membranes, the endo- and peri- 
theliomata, are occasionally met in the skin. They are related to — 

Sarcoma. — This tumor in its pure form is rather rare in the skin, in 
which it has been known to take any form. By far most frequently 
the melanotic form is seen. These tumors arise from nevi and develop 
in spindle cell or alveolar form. They contain atypical chromato- 
phores. A special form is the idiopathic multiple pigmented sarcoma 
of Kaposi, a disseminated variety of granulomatous and angiomatous 
nature. 

Epithelial tumors are the commonest new growths of the skin 
and appear as epitheliomata and glandular cancers. The former are 
divisible into those containing representatives of nearly all layers of 
the epiderm, squamous epithelioma, and those retaining the type of 
basal cells, basocellular epithelioma. 



THE SKIN 



1057 



The squamous epithelioma appears as a nodular growth, tending to 
ulcerate early, to spread out, and to be surrounded by a hard raised 
edge. It grows downward into the deeper tissues with finger-like pro- 
jections visible to the naked eye. The nests contain, viewed under 
magnification, chiefly prickle cells and elongated keratinized cells which 
when mashed together form pearly bodies. The commonest seats for 
this growth are where skin and mucous membranes join. Metastasis 
to the lymph-glands is common. 

Basocellular epithelioma occurs as separate masses in the skin, super- 
ficially seated or as distinct penetrating nodules. The clinico-patholog- 
ical varieties are as follows : 

Rodent ulcer is an epithelioma in which the actively growing tumor 
cells retain the shape and size of the basal cells of the rete malpighii. 
The cell masses are in the form of anastomosing columns, and have 
few or no pearls. The lesions known as Pagets disease of the nipple, 
so often succeeded by mammary cancer, also belongs in this category 
but the process seems to be more superficial. The epiderm is wide, 
its horny layer absent, the bulk being made up of large swollen epithelia 
resembling the deep rete layers but lacking in protoplasmic bridges; 
pearls are absent but liquefactive or coagulative necroses are seen. 
The corium is densely infiltrated, chiefly with plasma cells. 

Benign cystic epithelioma is one of the new growths retaining the 
basal cell characters, said by some to grow from sebaceous ducts, cyst 
by others from hair-follicles, and by still others from the rete of the 
surface epidermis. Hyperplasias of the epiderm penetrate the corium 
as round or irregular masses often with a central cavity containing 
debris. 

Lenticular carcinoma, or cancer en cuirasse, is that form which 
tends to spread under the skin, causing dense infiltration. It is usually 
secondary to cancer of the mamma. Carcinoma of the skin arises 
from its glands, and is discussed later. Secondary malignant tumors 
are not common in the skin. 

Structures Within the Skin 
sebaceous glands 

Seborrhea is a hypersecretion of sebaceous matter which may give 
rise to a scaly seborrhea siccum when a mixture of sebum and epidermal 
scales dry upon the surface, or seborrhea oleosa if the skin remains oily; 
dandruff and smegma in excess are respective examples. If protracted 
in duration and excessive in degree, a complete dermatitis may arise. 

Asteatosis is a deficiency of sebum, and is a constant companion of 
many dermatitides, but is rare as a primary process. 

Comedo is the accumulation of inspissated sebum held within the 
gland by a plug of epithelium, dried sebum, and dirt in the opening 
of the hair-follicle. The cause is probably a hyperplasia of the cells 
of the duct or a hyperkeratosis at its outlet, although it may have a 
deeper significance, since it is so constant at puberty as to be almost 
physiological at that time of great activity of the skin. If the hyper- 
plasia be prolonged, acne results. 

67 



1058 



A TEXT-BOOK OF PATHOLOGY 



Wens, or sebaceous cysts, may be considered as an exaggeration 
of the foregoing, the enlarged gland being surrounded by a connective- 
tissue capsule. 

Milium is the appearance of small pale masses lying just under the 
surface and probably of two fold nature. Some of them seem to be 
due to a hyperkeratinization of the follicular ducts of the small hairs 
while others are collections of sebum deep in a gland without a duct 
opening. 

Acne. — (See page 1050.) 

Tumors. — Adenomata, simple or of the cystic papillary type, and 
true carcinomata are known. 




Fig.[509. — Comedo, showing distention of duct'and slight glandular disintegration (greatly 
magnified) (courtesy of Dr. T. C. Gilchrist). 

SWEAT-GLANDS 

Hyperidrosis and anidrosis are respectively excessive and deficient 
or lacking sweat secretion. They may be associated with other dis- 
orders, but are obscure in origin otherwise. 

Bromidrosis, or malodorus sweat, is usually a peculiarity of an 
individual or due to some nervous disorder. 

Chromidrosis, colored sweat, is due to excretion of something taken 
into the stomach or to local bacterial infection. 

Sudamina is the eruption of tiny vesicles in the epidermis, due to 
blocking of sweat-gland ducts or their rupture as they pass through 
this layer. 

Inflammation of the sweat-glands is known as hydradenitis. 

Cysts and adenomata sometimes arise in sweat-glands. 



THE SKIN 



1059 



HAIR 

Hypertrichosis is excess of hair, and may be congenital, due to 
irritation locally or in women sometimes to a derangement or removal 
of the sexual organs. 

Alopecia is congenital absence of hair, or its disappearance during 
life. In the acquired form it may occur without apparent cause as the 
result of atrophy of the skin, or following acute infection. In the form 
of alopecia areata hair disappears in sharply outlined patches, leaving 
the skin smooth, flat, and dry. It may spread until all parts are de- 
nuded. There is atrophy and slight cellular infiltration of the skin, 
and the pigment is decreased. The hairs themselves are irregularly 
swollen, the medullary cells absent and air may be present in the shaft. 

Trichorrhexis is an unusual fragility of the hairs and is commonly 
due to bacterial or mycotic invasion into the shaft. 

Canities or loss of pigment in the hair may be congenital as in al- 
binism, premature in early grayness, physiological in senility, or if in 
patches may be due to local dermatitis or nervous disorders. The 
pigment disappears from the hair, but not necessarily from the follicles 
and air may be found in the shaft. 

NAILS 

The nails respond to slight injury by the appearance of white spots, 
probably due to air or small hemorrhages between the epithelial layers. 
Furrows across the nail occur after acute illness, or in delayed growth 
from any cause. Inflammation of the matrix {onychia) or its surround- 
ings {paronychia) is the result of causes similar to those given for derma- 
titis. It is commonest in syphilis and tuberculosis. Nails may be 
ribbed and distorted {onychogryphosis) , and penetrate the skin at the 
side, the so-called unguis incarnatus, or ingrowing nail. This may lead 
to inflammation or suppuration. 

Various inflammations — syphilis, favus, eczema — may involve the 
nail-bed. 

Tumors. — Fibroma, ecchondroma, and carcinoma may appear under 
the nails. 



INDEX 



Abderhalden's test, 285 
Abdominal pregnancy, 849 
Abortion, tubal, 848 
Abrin, poisoning from, 36 
Abscess, 139 

of brain, 962 

of cord, 982 

of heart, 507 

of liver, 695 

pathological anatomy, 695 

of lung, 589 

of prostate, 869 

of spleen, 463 

of thyroid gland, 736 

of tonsils, 633 

of vulva, 853 

retropharyngeal, 632 
Acanthosis, 1042 
Acapnia, 30 
Accidental carriers, 426 
Acephalocyst, 407 
Acervuloma, 212 
Acervulus, 751 

cerebri, 101 
Acetonuria, 801 
Achondroplasia, 884 
Achorion schonleinii, 367 
Achromatic substance, 942 
Acidosis, 44 

cryptogenic, 45 

experimental, 45 

in man, 45 
etiology, 45 
symptoms ? 46 
Acid-proof bacilli, 342 
Acne, 1050 

pancreatic, 724 

rosacea, 1052 

vulgaris, 1050 
Acrania, 937 
Acromegaly, 888 
Actinomyces bovis, 359 

madurse, 363 
Actinomycosis, 155, 359 

bodies, 361 
definition of, 359 

etiology of, 59 

of bones, 901 

of brain, 969 

of cheek, 628 

of heart, 518 

of intestines, 680 

of liver, 705 

of lungs, 605 

of lymphatic glands, 476 

of mouth, 627 

of muscles, 919 

of pericardium, 523 

of skin, 1054 

of thyroid gland, 741 



Actinomycosis, pathological anatomy, 
361 

physiology, 363 
Adami's modification of Hauser's theory 
of tumors, 167 

subinfection, 267 
Addison's disease, 746 
Adenocarcinoma, 228 

of mammary glands, 882 
Adenoma, 226 

appearance of, 226 

cystic, 229 

of mammae, 876 

definition of, 226 

destructive, 228 

etiology of, 226 

fetal, 738 

formation and structure of, 708 

malignant, 228 

nature of, 229 

of kidney, 783 

of liver, 707 

of lungs, 607 

of mammary glands, 879 

of suprarenal bodies, 747 

of uterus, 828 
malignant, 828 

of vulva, 854 

seats of, 226 

structure of, 227 
Adenomatous goiter, 738 
Adenomyositis, 827 
Adenosarcoma, 228, 783, 879 
Adhesions, formation of, 144 
Adipose tissue regeneration of, 160 
Affentuberculose, 466 
Agamodistomum ophthalmobium, 401 
Age in carcinoma, 231 

in disease, 19 
Agglutination, bacterial, 278 

in typhoid fever, 307 

theory of bacterial immunity, 272 
a-granules, 433 
Ague cake of malaria, 464 
Air in pericardium, 523 

respiratory, insufficiency of, in etiology 
of disease, 30 
Air-embolism, 69 
Albinism, 1023, 1044 
Albuminoid degenerations, 91 
Albuminous infiltration, 84 
Albuminuria, 801 

orthostatic, 802 
Albuminuric retinitis, 1027 
Albumosuria, 802 

Bence-Jones, 802 
Aleppo button, 388 
Aleukemic leukemia, 456 

lymphadenia, 477 
I Alexin, 268, 269, 279 
1061 



1062 



INDEX 



Alexin theory of immunity, 269 
Alimentary glucosuria, 51 

oxaluria, 54 
Alkaptonuria, 800 
Allergie, 282 
Alopecia, 1059 

areata, 1059 
Altmann's granules, 85 
Alveolar angiosarcoma, 209 

sarcoma, 199, 204 
Amboceptor, 268, 279 
Amebic dysentery, 670 
Amnesia, 956 
Amnion, 855 

Amphitrichous flagella, 257 
Amyelia, 982 

Amylaceous bodies of prostate, 870 
Amyloid formations, local, 99 
infiltration, 97 

definition, 97 

etiology, 97 

microscopical appearances, 98 
of arteries, 525 
of heart, 501 
of kidneys, 778 
of liver, 693 

of lymphatic glands, 469 

of mucosa of intestines, 661 

of pancreas, 719 

of pituitary body, 750 

of spleen, 465 

of stomach, 649 

of suprarenal bodies, 745 

of uterus, 824 

pathological anatomy, 98 

physiology, 99 
reactions, 98 
seats, 99 
Amyloidosis, 97 

Amyotrophic lateral sclerosis, 997 
Anal fissure, 665 
Anaphylactic shock, 282 
Anaphylaxis, 282 

Jobling's theory, 284 

Novy's theory, 285 

Vaughan's theory, 284 
Anaphylotoxin theory of infection, 284 
Anastomotic aneurysm, 538 
Anatomy, morbid, definition of, 17 

pathological, definition of, 17 
Anemia, 446 

aplastic, 452 

collateral, 62 

definition of, 446 

ictero-, hemolytic, 453 

local, 62 

of brain, acute, 952 

chronic, 952 
of bronchi, 556 
of conjunctiva, 1013 
of esophagus, 638 
of heart-muscle, 500 
of iris, 1023 
of kidneys, 754 
of larynx, 552 
of liver, 687 
of lungs, 562 
of mouth, 622 
of muscles, 912 



Anemia of pharynx, 631 
of pia-arachnoid, 924 
of retina, 1026 
of skin, 1044 
of spinal cord, 986 
of stomach, 641 
progressive pernicious, 450 
simple primary, 448 
splenic, 449, 460, 464 
j symptomatic, 446 
I Anemias, classification of, 446 
primary, 446, 448 
secondary, 446 
etiology of, 446 
pathological anatomy, 447 
physiology, 448 
Anemic infarct, 71 
Anencepaly, 940 
Anesthetic leprosy, 345 

shock, 25 
Aneurysm, 536 
anastomotic, 538 
cirsoid, 538 

conditions in other parts associated 

with, 542 
definition of, 536 
dissecting, 538, 541 
ectatic, 538 
etiology of, 536 
false, 536, 542 
miliary, 537 

of spinal cord, 986 
of arteries of brain, 950 
of heart, 516 

pathological anatomy, 538 
saccular, 538, 540 
spurious, 536, 542 
true, 536 
valvular, 517 
varicose, 542 
Aneurvsma racemosum seu cirsoideum, 
189 

Aneurysmal varix, 542 
Angina, 631 

herpetic, 631 

Ludovici, 637 

Ludwig's, 632 

pectoris, 512 

Vincent's, 358, 624, 635 
Angioma, 187, 189 

cavernoma, 189 

cavernosum, 189 

of bones, 901 

of liver, 706 

of skin, 1056 

of spleen, 466 

telangiectatic um, 189 
Angioneurotic edema, 80 
Angiosarcoma, 199, 209, 971 

alveolar, 209 

plexiform, 209 
Angiosarcomata myxomatodes, 210 
Angiosclerosis, 529 
Angular conjunctivitis, 1016 
Anhydremia, 440 
Anidrosis, 1058 

Animal, cold-blooded, sporozoa in, 394 
organisms, dermatitis due to, 1055 
parasites, diseases from, 382 



INDEX 



1063 



Animal parasites of intestines, 684 
of kidneys, 786 
of lungs, 609 

transmission of disease, 426 
Aniridia, 1023 
Anisocytosis, 436 
Ankyloglossia, 622 
Ankylosis of joints, 903 
Ankylostoma duodenale, 413 
Ankylostomiasis, 415 
Anlage, Baumgarten's, 19 
Annectant gyri, 939 
Annehdes, 421 
Annular synechia, 1023 
Anophthalmia, 1013 
Anteflexion of uterus, 812 
Anterior poliomyelitis, chronic, 998 

urethritis, 808 
Anterolateral column of Gowers, 981 
Ante version of uterus, 812 
Anthracosis, 105, 470, 585 
Anthrax, 326, 1052 

bacillus of, 326 

definition of, 326 

etiology of, 326 

of intestines, 680 

of muscles, 919 

pathological anatomy, 327 
physiology, 328 
Antibacterial immunity, 281 
Antibodies, 268 
Antigens, 268 

chemistry of, 285 
Antistreptococcus serum, 291 
Antitoxic immunity, 281 
Antitoxin, 273, 276 

action of, 274 

chemical nature, 274 

elimination of, 274 

tetanus, 325 

transmission of, 274 
Anuria, 799 

Aorta, stenosis and atresia of, 486 

Aphasia, 956 

Aphthous stomatitis, 623 

vaginitis, 851 
Aplasia, 82 
Aplastic anemia, 452 
Apnea, 30 

Apoplexia pulmonum vascularis, 562 . 

serosa, 954 
Apoplexy, 956 

pancreatic, 718 

placental, 856 
Appendicitis, 666 

interstitial, 668 

obliterating, 669 

pathological anatomy, 667 

relapsing, 668 
Arachnitis adhesiva, 980 
Arachnoid fluid, 974 
Arcus senilis, 1020 
Argyria, 106 
Arrhythmia, total, 506 
Arsenic, action of, 35 
Arterial disorders, 61 

hemorrhage, 65 

hyperemia, 63 
Arteries, 523 



I Arteries, amyloid infiltration, 525 
anatomical considerations, 523 
atrophy of, 524 
calcareous infiltration, 525 
congenital defects, 524 
embolism of, 912 
end-, 70 

fatty degeneration, 524 
hyaline degeneration, 525 
hypertrophy of, 524 
hypoplasia of, 524 
infectious diseases, 535 
inflammation of, 525. See also Arteri- 
tis. 

of brain, aneurysms of, 950 

hyaline degeneration of, 950 
syphilis of, 535 
tuberculosis of, 536 
Arteriocapillary fibrosis, 529 
Arteriolar sclerosis, benign, 772 
Arterioliths, 77 
Arteriosclerosis, 529, 950 

changes in other organs from, 534 
etiology of, 529 
Monckeberg's, 531, 534 
pathogenesis of, 529 
pathological anatomy, 532 
results of, 534 
Arteriosclerotic nephritis, 774 
Arteritis, 525 
acute, 525 

suppurative, 525 
Arthritis, acute, 904 

pathological anatomy, 904 
chronic, 905 
purulent, 905 
serous, 905 
deformans, 905 
atrophic form, 906 
clinical types, 907 
etiology, 905 
hypertrophic form, 906 
pathology, 906 
dry, 904 
fibrinous, 904 
gonorrheal, 808 
gouty, 908 

conditions associated with, 909 
neuropathic, 908 
purulent, 904 
rheumatoid, 905 
serous, 904 
tuberculous, 909 
Arthropoda, 421 
Ascaris lumbricoides, 411 
Ascending paralysis, Landry's, 992 

suppurative nephritis, 770 
Ascites, 726 

chylous, 726 
Asopia farinalis, 406 
Aspergillus fumigatus, 343 
Asphyxia, 30 

Aspiration pneumonia, 578, 581 
Asporogenous races, 256 
Asteatosis, 1057 
Asthma, thymic, 748 
Atavism, 22 

Ataxia, Friedreich's, 996 
Atelectasis, 565, 570 



1064 



INDEX 



Atelectasis, congenital, 570 

in later life, 571 _ 
Atelectatic bronchiectasis, 572 
Athelia, 874 

Atheromatous cyst, 869, 882 
Atmospheric pressure, decreased, in et- 
iology of disease, 29 
increased, in etiology of disease, 29 
Atomic dilatation of stomach, 650 
Atrio-ventriculo-bundle of His, 505 
Atrophic emphysema of lungs, 570 

gastritis, 644 
Atrophy, 82 

brown, 83 

definition of, 82 

etiology of, 82 

muscular, progressive spinal, 998 

numerical, 82 

of arteries, 524 

of bone-marrow, 481 

of bones, 895 

of brain, 964 

of choroid, 1025 

of ciliary body, 1024 

of glands of stomach, 948 

of head of optic nerve, 1031 

of heart, 513 

of iris, 1023 

of kidneys, 776 

of larynx, 554 

of liver, 689 

acute yellow, 691 

red, 687 
of lungs, 567 
of lymphatic glands, 468 
of mammary glands, 876 
of mouth, 626 
of muscles, 915 

myopathic, 916 

neuropathic, 915 
secondary, 916 

progressive, 915 

pseudohypertrophic, 916 

simple, 916 
of nerves, 1007 
of pancreas, 719 
of prostate, 869 
of retina, 1027 
of skin 1041 
of spleen, 464 
of testicle, 862 
of tongue and cheeks, 626 
of tympanic membrane, 1035 
of uterus ; 823 
pathological anatomy, 82 
pressure, 84 
senile, of brain, 964 

of uterus, 823 
simple, 82 
true, 82 

Auricular septum, defects of, 486 

tachycardia, 506 
Auriculitis, purulent, 1034 
Auriculoventricular orifices, stenosis and 

atresia of, 486 
Auto-intoxication, 24 
Autolysis, 83, 113 

Avascular tissues, phenomena of inflam- 
mation in, 123 



Avian tubercle bacillus, 333 

tuberculosis, 343 
Azur-granules, 434 

BABES-Ernst granules, 256 
i Bacillary dysentery, 670 
| Bacillus, 255 

acidi lactici, 298 
acid-proof, 342 
aerogenes capsulatus, 330 
Bordet-Gengou, of whooping-cough, 
318 

coli communis, 309 

cultivation, 310 

distribution, 310 

morphology, 310 

pathogenicity, 310 

pathological physiology, 311 

synonyms, 309 
comma, 347 
dysenteriae, 309 
enteritidis, 309 
figurans, 368 
Friedlander's, 347 
fusiformis, 358 
histolyticus, 331 
icteroides, 309, 369 
Klebs-Loffler, 299 
Koch- Weeks, 317 
lactis aerogenes, 298 
lacunatus, 317 
Lustgarten's, 351 
Morax-Axenfeld, 317 
Neapolitanus, 310 
cedematis maligni, 329 
of anthrax, 326 
of cholera, 347 
of diphtheria, 299 
of Ducrey and Unna, 320 
of dysentery, 311 
of infectious emphysema, 330 
of influenza, 312 ' . 

organisms resembling, 317 
pathological lesions induced by, 313 
of leprosy, 343 
of malignant edema, 329 
of typhoid fever, 303 
ozcenae, 298 
perfringens, 330 

phlegmones emphysematosa, 331 

proteus, 368 

psittacosis, 309 

putrificus coli, 331 

pyocyaneus, 347 

pyogenes fcetidus, 310 

rhinoscleromatis, 298 

Schaudinn's, 351 

smegma, 342 

sporogenes, 331 

tetani, 323 

tuberculosis, artificial culture, 334 
avian, 333 
bovine, 333 
demonstration, 334 
distribution, 335 
human, 332 
modes of infection, 335 
typhi abdominalis, 303 
Bacony spleen, 465 



Bacteremia, 266 
Bacteria, action of, 253 

Bail's theory of virulence, 265 

biology of, 257 

chemical conditions of growth, 258 
chemistry of, 257 
chromogenesis of, 263 
classification of, 253 

of diseases due to, 39 
conditions of growth, 258 
diseases due to, 286 
effect of electrical currents on, 258 

of heat on, 258 

of light on, 258 

of toxic products of, 264 
entrance into body, 40 
etiological relationship of, to disease, 39 
facultative, 258 
fast, 267 

fate of toxins of, 262 
ferments of, 260 
fixed, 267 
functions of, 259 
higher, diseases due to, 359 
history of, 253 
in kidneys, 785 
involution forms, 257 
Koch's laws of specificity, 39 
local effects, 263 

mechanical conditions of growth, 258 
morphology of, 255 
nature of, 253 

not causing specific infection, 367 
obligate, 257 

aerobic, 258 
pathogenic, 257 
photogenesis of 2 263 
physical conditions of growth, 258 
products of, 259 

in culture-medium, 262 
proteins of, 259 
toxic products, 36 
toxins of, 261 

fate, 262 

tumors and, connection between, 168 
Bacteriaceae, 254 
Bacterial agglutination, 278 
theory of immunity, 272 
immunity, 277 

as applied to bacteriolysis, 278 
to cytolysis, 278 
protein, 287 
toxins, 39 
Bacteriolysins, 271 

Bacteriolysis, bacterial immunity as 
applied to, 278 

Pfeiffer's, explanation of, 279 
Bacteriolytic theory of immunity, 270 
Bacterium anthracis, 326 

bulgaricum, 347 

coli commune, 309 

diphtheriae, 299 

mucosum capsulatum, 298 
group, 346 

pestis, 318 

pneumoniae of Friedlander, 297 
rhinoscleromatis, 155, 322 
Bacteriuria, 804 

Bail's theory of virulence of bacteria, 26£ 



INDEX 1065 

Balanitis, 860 
Balantidium coli, 396 

minutum, 396 
Ball thrombi, 76, 488 
Balloon cells, 1045 
Banti's disease, 464 
Basocellular epithelioma of skin, 1057 
Basophiles, 432 
Baumgarten's anlage. 19 
Bednar's aphthae, 623 
Beef tapeworm, 404 
Beer-drinker's liver, 701 
Beggiatoaceae, 254 
Bence-Jones albumosuria, 802 
Benign fungus of testicles, 864 
Beriberi, 58 

etiology of, 58 
Bile-ducts, dilatation of, 713 
dropsy of, 714 
stenosis of, 713 
Bilharzia, 399 
Bilharziasis, 399 
Biliary cirrhosis, 697, 701 
obstructive, 702 
ducts, inflammation of, 711. See also 

Cholangitis. 
tract ? tumors of, 716 
Bilirubin in urine, 806 
Bilocular heart, 485 
Biology of bacteria, 257 
Birds, sporozoa in, 394 
Black tongue, 626 

Bladder, acquired malformations of, 792 
calculi in, 795 

results of, 797 
carcinoma of, 799 
changes of position of ; 792 
congenital malformations of, 791 
dilatation of, 792 
exstrophy, 791 
false diverticula of, 792 
fibroma of, 799 
foreign bodies in, 795 
hemorrhages of, 793 
•hyperemia of, 793 
inflammation of, 793 
papillomata of, 797 
polypoid outgrowths of, 797 
rupture of, 792 
syphilis of, 795 
tuberculosis of, 795 
' tumors of, 797 
Blastomyces dermatitidis, 365 
Blastomycetes in cause of tumors, 169 
Blastomycosis, 365, 1055 
Blebs, 1045 
Bleeders, 67 
Blepharitis, 1032 

Blood, alterations in, as cause of edema, 
80 

of thrombosis, 74 
anatomy of 429 
changes in, 61 

character of, in leukocytosis, 445 
coagulation of, 74 
crises, 437 
destruction, 118 
diseases of, 429 
I disturbances of circulation, 60 



1066 



INDEX 



Blood, foreign bodies in, 457 
formation of, 435 
parasites in, 458 
plasma of, 429, 435 
hyperinosis of, 439 
hypinosis of, 439 
pathological changes in, 439 
vegetable parasites in, 458 
Blood-current, alterations in, as cause of 

thrombosis, 73 
Blood-plaques, 435 

conglutination of, 75 
Blood-platelets, 435 
Blood-poisons, poisoning from, 34, 37 
Blood-pressure, increase of, as cause of 
edema, 79 
of hemorrhage, 66 
Blood-serum, hypertonicity of, 439 
Blood-vessels, changes in, in inflamma- 
tion, 124 

diseases of, causing hemorrhage, 66 

new formation, in regeneration, 159 

of brain, syphilis of, 969 

walls, changes in, as cause of throm- 
bosis, 73 
Bodo urinarius, 385 
Boils, 140 
Bone sand, 898 
Bone-marrow, 479 

anatomical considerations, 479 

atrophy of, 481 

chloroma of, 483 

degenerations of, 481 

fatty infiltration, 481 

hypertrophy of, 481 

in leukemia, 482 

inflammation of, 482 

mucoid degeneration, 481 

myeloma of, 483 

necrosis of, 481 

pigmentation of, 481 

tumors of, 483 
Bones, actinomycosis of, 901 

anatomy of, 883 

angioma of, 901 

atrophy of, 895 

carcinoma of, 902 

caries of, 894 

fractures of, 888 

chloroma of, 902 

chondroma of, 901 

cold abscesses of, 898 

cysts of, 902 

degenerative conditions of, 894 
development of, 883 
diseases of, 883 

disorders of development of, 883 
enostoses of, 901 
exostoses of, 901 
fibroma of, 901 
giant growth of, 888 
gummata of, 900 
hemorrhage from, 889 
hyperemia of, 889 
hypertrophy of, 888 
hypoplasia of, 895 
inflammations of, 889 
infractions of, 885 
intermediary callus of, 888 



Bones, involucrum of, 891 
lepra of, 901 

myelogenous callus of, 887 
myeloma of, 902 
myxoma of, 901 
necrosis of, 894 

conditions associated with, 895 

definition, 894 

etiology of, 894 

pathological anatomy, 894 
osteoma of, 901 
parasites of, 902 
periosteal callus of, 887 
regeneration of, 159 
sarcoma of, 901 
sequestrum of, 894 
syphilis of, 899 

conditions associated with, 900 

congenital, 900 

pathological anatomy, 899 
thrombosis of, 889 
tuberculosis of, 897 

conditions associated with, 899 

etiology, 897 

pathological anatomy, 898 

seats of, 899 
Bordet-Gengou bacillus of whooping- 
cough, 318 
Botrvomvcosis, human, 367 
Botulism', 39 

Bovine tubercle bacillus, 333 
of pearl disease, 150 
tuberculosis, 336 
Bow-legs, 903 

Brain, abnormalities in size, 938 
abscess of, 962 
absence of, 940 
actinomycosis of, 969 
anatomy of, 933 
anemia of, acute, 952 

chronic, 952 
arteries of, 949. See also Arteries of. 

brain. 

blood-vessels of, syphilis of, 969 
carcinoma of , 971 
circulatory disturbances of, 951 
compression of, 968 
concussion of, 967 
congenital abnormalities, 937 
development of, 933 
edema of, 953 
embolism of, 957 
fibroma of, 971 
glioma of, 969 
gumma of, 969 
hemorrhage of, 954 
hyperemia of, 952 
hypertrophy of, 938 
hypoplasia of, 939 
lacerated wounds of, 967 
lipoma of, 901 
lymphangioma of, 971 
osteoma of, 971 
physiology of, 935 
primary vesicles of, 932 
psammoma of, 971 
red softening of, 958 
sarcoma of, 970 
sclerosis of, atrophic, 948 



INDEX 



1067 



Brain, sclerosis of, diffuse, 948 
disseminated, 948, 964 
hypertrophic nodular, 949 
multiple, 964 

senile atrophy of, 964 

substance, inflammation of, 959 

thrombosis of, 957 

tuberculosis of, 968 

tumors of, 969 

white softening of, 958 

yellow softening of, 958 
Brain-sand, 751 
Bread-and-butter pleurisy, 614 
Breast. See Mammary Glands. 
Bright's disease, 756 
Brill's disease, 375 
Bromidrosis, 1058 
Bronchi, 556 

anatomical considerations, 556 

anemia of, 556 

congenital malformations, 556 

dilatation of, 559 

foreign bodies in, 561 

hemorrhage of, 556 

hyperemia of, 556 

infectious diseases, 561 

inflammation of, 557. See also Bron- 
chitis. 

obstruction of, 559 

parasites of, 561 

stenosis of, 559 

syphilis of, 561 

tuberculosis of, 561 

tumors of, 561 

ulcers of, 558 
Bronchiectasis, 558, 559 

atelectatic, 572 

cylindrical, 560 

fusiform, 560 

saccular, 560 
Bronchiolectasis, 560 
Bronchiolitis, 580 

exudativa, 558 
Bronchitis, acute catarrhal, 557 

capillary, 557, 580 

chronic catarrhal, 557 

fetid, 557 

fibrinous, 558 
Bronchogenic purulent pneumonia, 558 

tuberculosis, 591, 592 
complications in, 599 
Bronchopneumonia, 572, 578 

associated lesions, 581 

definition of, 578 

etiology of, 578 

pathogenesis of, 580 

pathological anatomy, 579 

simple, 579 

unusual characters, 581 
terminations, 581 
Bronchorrhea, 557 
Brown atrophy, 83 
Bubo, 471, 809 
syphilitic, 354 
tertiaris, 476 
Bubonic plague, 318 
definition, 318 
etiology, 318 

pathological anatomy, 319 



Bubonic plague, pathological physiology, 
320 

septicemic form, 320 
Buchner's alexin, 269, 279 
Bulb, optic, abnormalities in position of, 
1031 

Bulbar paralysis, 1000 
Bullae, 1045 

Bullous emphysema of lungs, 569 

keratitis, 1019 
Bundle of His, 484 
Bursas, inflammation of, 911 
Bursitis, 911 

Cachectic leukocytosis, 444 
Cachexia of malignant tumors, 174 

strumipriva, 741 
Calcareous infiltration of arteries, 525 

of pia arachnoid, 979 
Calcicosis, 105 
Calcification, 101 

after thrombosis, 77 

definition of, 101 

etiology of, 101 

metastatic, 102 

of choroid plexus, 973 

of kidneys, 777 

of lymphatic glands, 470 

of muscles, 918 

of placenta, 856 

of spleen, 465 

of stomach, 649 

of testicles, 863 

of veins, 542 

pathological anatomy, 102 
physiology, 104 

seats of, 103 
Calculi, 105 

in bladder, 795 

in pelvis of kidney, 788 

pancreatic, 725 

urinary, results of, 797 
Callus, 887 

intermediary, 888 

myelogenous, 887 

periosteal, 887 
Canalization of thrombus, 77 
Cancer en cuirasse, 882, 1057 
Cancer-juice, 881 
Canities, 1059 

Capillary bronchitis, 557, 580 
hemorrhage, 65 

walls, increased permeability of, as 
cause of edema, 80 
Capsular cataract, 1021 
Capsulo-lenticular cataract, 1021 
Carbohydrate metabolism, diseases of, 50 
Carbonates in urine, 806 
Carbuncles, 140, 1052 
Carcinoma, 229 

age in, 231 

appearance of, 231 

basocellulare, 237 

colloid, 235, 242, 243 

congenital theory, 230 

definition of, 229 

degenerative changes in, 235 

encephaloid, 240 

endothelial, 211 



1068 

Carcinoma, epidermoid, 238 
etiology of, 230 

formation and structure of, 708 

gelatinous, 242 

glandular, 240 

heredity in, 231 

infectious theory, 230 

lenticular, of skin, 1057 

lupus, 627 

medullary, 240 

nature of, 235 

of bladder, 799 

of bones, 902 

of brain, 971 

of esophagus, 640 

of Fallopian tubes, 847 

of intestines, 682 

of kidneys, 783 

of larynx, 555 

of liver, 708 

secondary, 709 
of lungs, 607 
of lymphatic glands, 479 
of mammary glands, 880 
of ovary, 839 
of pancreas, 723 

pathological physiology, 724 
of penis, 861 
of peritoneum, 732 
of pleura, 621 
of prostate, 873 
of seminal vesicles, 874 
of spinal cord, 1005 
of spleen, 466 
of stomach, 651 

pathological physiology of, 655 
of testicles, 868 
of trachea, 556 
of urethra, 810 
of uterus, 830 
of vagina, 852 
of vulva, 854 

pathological physiology, 236 

sarcomatodes, 234 

scirrhous, 240 

seats of, 232 

special forms, 242 

structure of, 232 

traumatic theory, 230 

varieties of, 236 
Carcinomatosis, 732 

general, 232 
Carcinomatous cylindroma, 243 
Cardiac decompensation, 64 
Cardioliths, 77 
Carditis, 506 
Caries of bones, 894 

of teeth, 629 
Carnification of lungs, 572 
Carotid body, 752 
Carriers, 426 

accidental, 426 

chronic, 426 

hidden, 426 

infected, 426 

typhoid, 306 
Cartilage, regeneration of, 159 
Caruncle of vulva, 854 
Casease, 261 



INDEX 

Caseation, 116 

of testicles, 863 
Caseous necrosis, 148 
Cataract, 1021 

capsular, 1021 

capsulo-lenticular, 1021 

lenticular, 1021 

Morgagnian, 1022 
Catarrh, acute nasal, 550 

scrofulous, 550 

sinus, 471 

spring, 1014 

suffocative, 559 
Catarrhal bronchitis, acute, 557 
chronic, 557 

conjunctivitis, acute, 1014 

endometritis, acute, 817 

ent ritis, 664 

esophagitis, 638 
chronic, 638 

inflammation, 141 
acute, of vagina, 850 
of vulva, 853 

jaundice, 666, 717 

laryngitis, acute, 552 
chronic, 552 

nephritis, 762 

otitis media, 1036 

pharyngitis, 631 
chronic, 631 

pneumonia, 572, 578 

stomatitis, 622 

tonsillitis, 633 

vaginitis, acute, 850 
chronic, 851 
I Cattle, Texas fever of, 393 
Caustics, action of, 34 
Cavernous angioma, 189 

lymphangioma, 188 
Cecitis, 666 

Cecum, inflammation of, 666 
Cell, baUoon, 1045 

chromaffin, 213 

contents, 255 

division, abnormal, 157 

dust, 585 

edema of, 100 

epithelioid, 147 

formative, 158 

giant-, foreign body, in inflammation, 
132 

in inflammation, 129 

parenchymatous, 132 
heart-failure, 564 
inclusion, 1015 
irritation, 433 
lepra, 154 
leukocytoid, 158 
lymphoblastic, 468 
Mikulicz, 322 
of Leydig, 861 

phagocytic, large mononuclear, in in- 
flammation, 128 

plasma-, 433, 468 
in inflammation, 129 
of Unna, 129 
of Waldeyer, 129 

Purkinje, 484 

stimulation, 433 



INDEX 



1069 



Cell, syncytial, 251 
Cell-membrane, 256 

Cellular and attraction theory of inflam- 
mation, 122 
degenerations, secondary, in inflamma- 
tion, 133 
Cellulitis, 1053 
Cephalo-hematoma, 889 

internal, 920 
Cercarise, 398 
Cercomonas hominis, 385 

urinarius, 385 
Cerebellum, hypoplasia of, 939 
Cerebral hemispheres, hypoplasia of, 939 
hemorrhage, 954 

pathological physiology, 956 
secondary degeneration after, 956 
Cerebrospinal fluid, 974 
hypersecretion of, 972 
meningitis, 974 
epidemic, 927 
Cervix, chronic, endometritis of, 819 
phagedenic ulceration of, 820 
uteri, hypertrophy of, 824 
syphilis of, 823 
Cestodes, 401 
Chalazion, 1032 
Chalicosis, 585 
Chancre, 353 
of penis, 860 
of syphilis, 152 
soft, 320 

definition of, 320 
etiology of, 320 
pathological anatomy, 321 
physiology, 321 
Chancroid, 320 
of penis, 860 
of vulva, 854 
Charcot-Le'yden crystals, 558 
Cheeks, actinomycosis of, 628 

atrophy of, 626 
Cheesy pneumonia, 572, 582 
Chemical processes involved in inflamma- 
tion, 130 
Chemistry of bacteria, 257 

pathological, definition of, 17 
Chemotaxis, 126 
negative, 126 
positive, 126 
Chicken-pox, 375 
Chilblain, 29 

Chlamydobacteriacese, 254 
Chlamydozoa, 113, 380 
Chloroma, 197 

of bone-marrow, 483 

of bones, 902 
Chlorosis, 449 

blood in, 450 

definition of, 449 

etiology of, 449 

in male, 449 

late, 449 

pathological anatomy, 449 
physiology, 450 
Choked disk, 1031 
Cholangitis, chronic, 712 
results, 713 
suppurative, 712 



Cholecystitis, 713 

Cholelithiasis, 714. See also Gall-stones. 
Cholera, 347, 672 

associated conditions, 672 

bacillus of, 347 

causes of, 349 

definition of, 347 

etiology of, 347 

pathological anatomy, 349, 672 
physiology, 349 

vibrio, organisms resembling, 350 
Cholerase, 272 
Cholesteatoma, 249 

of middle ear, 1038 

of pia-arachnoid, 931 
Cholesterin deposits, 104 

in urine, 806 
Choluria, 801 

Chondrodystrophia fetalis, 884 
Chondroma, 182 

appearance of, 183 

definition of, 182 

etiology of, 183 

nature of, 185 

of bones, 901 

of lungs, 606 

of mammary glands, 878 

of pleura, 620 

of testicles, 867 

osteoid, 184 

seats of, 184 

structure of, 184 
Chordoma, 219 

Chorioepithelioma of testicles, 868 
Chorion, 855 

Chorionephithelioma, 250 
Choroid, 1013, 1025 
atrophy of, 1025 
hemorrhage in, 1025 
inflammation of, 1025 
plexus, 972 

calcification of, 973 
degenerations of, 973 
cysts of, 973 
hemorrhage into, 972 
infectious diseases of, 972 
inflammation of, 972 
tuberculosis of, 972 
tumors of, 973 
ruptures of, 1025 
syphilis of, 1026 
tuberculosis of, 1026 
tumors of, 1026 
wounds of, 1025 
Choroiditis, 1026 
chronic, 1026 
diffuse, 1026 
purulent, 1026 
serous, 1026 
Chromaffin cells, 213 

tumor, 217 
Chromatophoroma, 207 
Chromidrosis, 1058 
Chromogenesis of bacteria, 263 
Chyliform ascites, 727 
Chylous ascites, 726 
effusion in pleura, 611 
hydropericardium, 519 
Chyluria, 804 



1070 



INDEX 



Cicatrices fistuleuse, 599 
Cicatrix, 144 
Ciliary body, 1013 
atrophy of, 1024 
cysts of, 1025 
inflammation of, 1024 
syphilis of, 1025 
tuberculosis of, 1025 
tumors of, 1025 
Circulation, lymphatic, obstruction 
as cause of edema, 80 
of blood, disturbances of, 60 
Circulatory system, diseases of, 484 
Cirrhosis, biliary, 697, 701 
Hanot's, 701 
Laennec's, 697 
obstructive biliary, 702 
of liver, 696 
of pancreas, 721 
pigmentary, 702 
portal, 697 
syp ilitic, 703 
toxic, 703 
tuberculous, 703 
varieties of, 697 
Cirsoid aneurysm, 538 
Clap-threads, 809 
Clasmatocytes, 128 
Cleft fungi, 253 

palate, 622 
Clonorchis endemicus, 401 

sinensis, 399 
Cloudy swelling, 84, 101, 691, 776 
definition, 84 
etiology, 84 
of heart, 500 
pathological anatomy, 85 

physiology, 86 
seats of, 86 
Club-foot, 903 i 
Coagulating ferments, 261 
Coagulation necrosis, 113 
definition, 113 
etiology, 113 
morbid physiology, 114 
of blood, 74 
of muscles, 918 
pathological anatomy, 113 
Coal-dust pigmentation, 105 
Coccaceae, 254 
Cocci, disease due to, 286 
Coccidia, 394 

Coccidioidal granuloma, 1055 
Coccidioides immitis, 366 
Coccidiosis, 366 
Coccidium cuniculi, 394 

hominis, 395 

perforans, 395 
Coccus, 255 
Cohnheim's emigration theory of inflam- 
mation, 122 

theory of tumors, 166 
Cold in etiology of disease, 28 
Colitis, 669 
Collateral anemia, 62 

hyperemia, 63 
Colloid cancer, 235, 242, 243 

cystomata of ovaries, 836 

definition of, 96 



Colloid cancer, degeneration, 96 
definition, 96 
etiology, 96 

microscopic appearance, 96 
pituitary body, 750 
pathological anatomy, 96 
physiology, 97 
goiter, 737 
Coloboma, 1013, 1022 
Colored sweat, 1058 
Colpitis, 850 
Column of Burdach, 982 

of Gowers, anterolateral, 981 
Combined sclerosis, 1000 
Comedo, 1057 
Comma bacillus, 347 
Commotio cerebri, 25 
Communicable diseases, 40 

methods of transmission, 423 
Compensatory emphysema of lungs, 568 
Complement, 268, 279 
deviation, 281, 282 
fixation, 281, 282 
Compression of brain, 968 
Concrements, 105 

Concretions in uriniferous tubules, 779 

of seminal vesicles, 874 

prostatic, 870 
Concussion of central nervous svstem, 
967 

of brain, 967 
Condyloma acuminatum of penis, 860 

latum, 354 

of syphilis, 152 
Congenital cystic hygroma, 188 

defects of esophagus, 637 
of stomach, 641 

hydrocephalus internus, 976 

malformations of pharynx, 630 
of tonsils, 630 

ptosis, 1013 

sclerosis, 938 

svphilis, 356 
of bones, 900 

theory of carcinoma, 230 
Congestion, active, 63 

hypostatic, 60, 63 
of lungs, 564 

of lungs, 562 

of ovary, 834 

passive, of esophagus, 638 
i Conglutination of blood-plaques, 75 
Conjunctiva, 1012 

anemia of, 1013 

cysts of, 1018 

degenerations of, 1014 

edema of, 1014 

hemorrhage of, 1014 

hyperemia of, 1013 

inflammations of, 1014 

syphilis of, 1017 

trachoma of, 1015 

tuberculosis of, 1017 

tumors of, 1018 
Conjunctivitis, angular, 1016 

catarrhal, acute, 1014 

follicular, 1015 

Parinaud's, 1016 

phlyctenular, 1016 



INDEX 



1071 



Conjunctivitis, pseudomembranous, 1014 

purulent, 808 

vernal, 1014 
Connective tissue, fibrous, regeneration 

of, 158 

Connective-tissue tumors, 176 
of ovaries, 835 
of stomach, 651 
Constitutional dyscrasia, 165 

syphilis, 354 
Consumption, galloping, 594 
Contagious diseases, 39 
Contraction of gall-bladder, 714 
Contrecoup, hemorrhage by, 967 
Coolie itch, 414, 415 
Copula, 268 
Cor bovinum, 516 

villosum, 520 
Cord, anatomy, 932 

development of, 932 

double, 982 

spinal, glioma of, 1005 

unusual length of, 983 
Corectopia, 1022 
Corium, 1040 

inflammations of, 1052 
Cornea, 1012, 1018 

cysts of, 1020 

inflammations of, 1018 

leprosy of, 1020 

syphilis of, 1020 

tuberculosis of, 1020 

tumors of, 1020 

wounds of, 1020 
Corns, 1042 

Coronary artery, embolism of, 489 

thrombosis of, 489 
Corpora amylacea, 98 
Corpus calosum, 939 

fibrosum, 834 

luteum, 834 

of pregnancy, 834 
Corpuscles, dust, 436 

red, 429. See also Erythrocytes. 

shadow, 437 

white, 431. See also Leukocytes. 
Coryza, 550 
Cowper's glands, 873 
Craniopagus, 251 
Cranioschisis, 938 
Craniotabes, 885 
Craw-craw, 420 
Cretinism, 742, 884 
Crisis in croupous pneumonia, 296 
Croup, false, 552 
Croupous enteritis, 664 

inflammation, 136 

laryngitis, 553 

pneumonia, 294, 573 
crisis in, 296 
definition, 294 
etiology, 294 

pathological anatomy, 296 
physiology, 296 
stomatitis, 623 
Crusts, 1046 

Cryptogenetic osteomyelitis, 482 
Cryptogenic acidosis, 45 
Cryptophthalmia, 1013 



Cryptorchismus, 862 
Crystalline lens, 1021 

congenital abnormalities of, 1021 
dislocation of, 1022 
luxation of, 1022 
Culex fatigans, 378 
Currant-jelly clots, 488 
Curschmann's spirals, 558 
Cutaneous horns, 1042 
Cutis, 1040 
Cyanosis, 64 

congenital, 487 
Cyanotic induration of lungs, 564 
of spleen, 461 
\ Cyclasterion scarlatinale, 373 
i Cyclencephaly, 938 
; Cyclitis, 1024 
Cyclopia, 938, 1013 
Cylindrical epithelioma, 240 
bronchiectasis, 560 
j Cylindro-adenoma, 229 
Cylindroma, 210, 229 
carcinomatous, 243 
endotheliomatous, 210 
sarcomatous, 210 
Cyst, atheromatous, 869 

dermoid, 247 
Cystadenoma, 229, 880 
Cystic accumulations in lesser omental 
cavity, 724 
adenoma, 229 

of mammae, 876 
degeneration of ovary, 836 
disease of breast, 880 
epithelioma, 238 
goiter, 737 

hygroma, congenital, 188 
lymphangioma, 188 
otitis, 1038 

tumors of ovaries, 836 
J Cysticerci, racemose, 404 
| Cysticercus cellulosae, 404 
Cystin in urine, 806 
Cystinuria, 802 
Cystitis, 793 

chronic, 794 

mucopurulent, 793 

phlegmonous, 794 

pseudomembranous, 794 
Cystocele, vaginal, 849 
Cystoids, 243 

Cystoma, colloid, of ovaries, 836 

glandular, of ovaries, 836 

papillary, of ovaries, 837 

papuliferous, 245, 868 

proliferative, 245 
Cystosarcoma, 879 
J Cysts, 243 

classification of, 243 

daughter-, 409 

definition of, 243 

dermoid, of ovaries, 839 

due to foreign bodies, 244 

echinococcus, 407 
seats of, 410 

epithelial, 244 

granddaughter-, 409 

hydatid, 409 
! of antenatal origin, 252 



1072 



INDEX 



Cysts of bones, 902 

of choroid plexus, 973 

of ciliary body, 1025 

of conjunctiva, 1018 

of cornea, 1020 

of dura mater, 923 

of epiglottis, 555 

of Fallopian tubes, 847 

of iris, 1024 

of kidneys, 784 

of Kobelt's tubules, 840 

of liver, 709 

of lungs, 609 

of mammary glands, 882 

of pancreas, 724 

of parovarium, 840 

of pituitary body, 750 

of prostate, 873 

of scrotum,. 861 

of spinal cord, 1005 

of spleen, 466 

of uterus, 833 

of vagina, 852 

of vulva, 854 

proliferation, 244 

retention, 243 

sebaceous, 1058 

softening, 243 

true, 243 
Cytase, 268, 270 
Cytolysin, 280 

Cytolysis, bacterial immunity as applied 

to, 278 
Cytophile, 268 

Cytoryctes variolse seu vaccinae, 374 

Dacryo-adenitis, 1018 
Dacryocystitis, 1018 
Daughter-cysts, 409 
Davainea madagascariensis, 406 
Decidua, 855 

anatomical considerations, 855 

reflexa, 855 

serotina, 855 

vera, 855 
Deciduoma malignum, 250 
Decompensation, cardiac, 64 
Defective development as cause of 

tumors, 166 
Defects, congenital, of esophagus, 637 
Deficiency diseases, 41 
Degeneration, 84 

albuminoid, 91 

colloid, 96. See also Colloid degene- 
ration. 
dropsical, 100 

fatty, 88. See also Fatty degeneration. 
hyaline, 92. See also Hyaline degene- 
ration. 
inflammation, 142 

mucoid, 94. See also Mucoid degene- 
ration. 
of bone-marrow, 481 
of conjunctiva, 1014 
of lymphatic glands, 469 
of mouth, 626 
of mucous membrane, 626 
of nerves, 1007 
of placenta, 856 



Degeneration of pyramidal tract, 956 
of spinal cord, in white matter, 1000 
primary, 992 
secondary, 1003 
of spleen, 464 
parenchymatous, 84 

of liver, 691 
pigmentary, of retina, 1028 
secondary cellular, in inflammation, 
133 

Degenerative changes in tissues in inflam- 
mation, 133 

conditions of bones, 894 

fatty infiltration, 91 

tubular nephritis, 762 
Deglutition pneumonia, 578 
Dengue, 378 
Dental osteoma, 187 
Dermacentor venustus, 380, 422 
Dermal leukemia, 454 
Dermatitis, 1045 

due to animal organisms, 1055 
Dermatographia, 1045 
Dermatomycosis, 367 
Dermatomyositis, 914 
Dermoid cyst, 247 
of ovaries, 839 
of testicles, 869 
Descemet's membrane, 1012 
Desmon, 268 

Destructive adenoma, 228 

epithelial tumor of placental site, 250 

placental polyps, 858 
Dextrocardia, 486 

5-granules, 434 
Diabete bronze, 54, 107 
Diabetes, etiology of, 52 

mellitus, 51 

metabolism in, 54 

pathogenesis of, 52 

pathological anatomy, 54 

phosphaticus, 55 

renal, 53 
Diabetic retinitis, 1027 
Diaceturia, 801 
Diapedesis, 65 

of red corpuscles in inflammation, 127 
l Diaphragmatic hernia, 650, 658 
! Diarrhea, 396 
Diastematomyelia, 982 
Diastatic ferments, 260 
Diathesis, hemorrhagic, 67 
Dibothriocephalus cordatus, 410 

latus 403, 410 
Dicephalus, 252 

Diffuse nephritis, sclerosis secondary to, 
771 

Dilatation of bile-ducts, 713 
of bronchi, 559 
of esophagus, 639 
of Fallopian tubes, 842 
of gall-bladder, 714 
• of heart, 514 
of intestines, 657 
of lymphatic vessels, 546 
of stomach, 650 

atonic, 650 
of thoracic duct, 547 
of ureter, 786 



INDEX 



1073 



Dilatation of uterus, 815 

of veins, 544 
Diphtheria, 299 

definition of, 299 

distribution of bacilli in, 301 

etiology of, 299 

internal lesions in, 301 

mixed infection in, 300 

of animals, 301 

of pharynx, 634 

of vulva, 853 

pathological anatomy, 301 
physiology, 302 

predisposing causes, 300 

Schick test in, 300 

visceral lesions in, 301 
Diphtheria-like bacilli, 302 
Diphtheritic endocarditis, 492 

inflammation, 135, 136 

laryngitis, 553 

rhinitis, 550 

salpingitis, 844 
Diplococcus in other diseases, 296 

meningitidis, 291 

pneumoniae, 294, 573 
cultivation, 294 
pathogenicity, 294 
Diplogonoporus grandis, 411 
Dipylidium caninum, 406 
Disease, Addison's, 746 

age in, 19 

cold in, 20 

conditions of life in, 20 
definition of, 17 
determining causes, 24 
etiological relationship of bacteria to, 
39 

etiology, 19 

foot-and-mouth, 623 

habitation in, 20 

heat in, 20 

idiosyncrasy in, 20 

injury in, 20 

nutrition in, 20 

occupation in, 20 

pathological disposition to, 21 

physical forces in, 21 

poisons in, 21 

predisposing factors, 19 

race in, 20 

sex in, 20 

symptoms of, 18 

transmission of, by animals, 426 

by fomites, 427 

by food, 425 _ 

by human beings, 426 

by inanimate objects, 427 

by insects, 426 

with cycle of development in 
intermediate host, 427 

by soil, 425 

by water, 425 

direct, 424 

indirect. 425 
Diseases, infectious, 626 

of pharynx, 634 
of islands of Langerhans, 719 
of joints, 903 
of salivary ducts, 637 
68 



Diseases of voluntary muscles, 912 
Disintegration, granular, 86 
Dislocation of crystalline lens, 1022 

of joints, 903 
Dissecting aneurysm, 538, 541 
Distomum haematobium, 399 

hepaticum, 398 
Distortions of joints, 903 
Diverticula, false, of bladder, 792 

of esophagus, 639 

of intestines, 656 
Dourine, 387 

Dracunculus medinensis, 417 
Dropsical degeneration, 100 
infiltration, 100 
of liver, 694 
Dropsy of bile-ducts, 714 
of gall-bladder, 714 
of joints, 904 
of pericardium, 519 
of peritoneum,, 726 
of pleural cavity, 611 
Drowning^ 30 
Dry arthritis, 904 

gangrene, 118 
Ducrey and Unna, bacillus of, 320 
Ductless glands, diseases of, 734 

physiologic considerations, 734 
Ductus Botalli, patulous, 487 
Dumdum fever, 388 
Duodenitis, 666 
Dura mater, 920 
cysts of, 923 
diseases external to, 978 
diseases of, 978 
fatty infiltration of, 978 
hemorrhage of, 920, 978 
hyperemia of, 920 
inflammation of, 921 
sinus thrombosis of, 920 
syphilis of, 922, 979 
tuberculosis of, 922 
tumors of, 922, 979 
Durham-Gruber phenomenon in typhoid 
fever, 307 

Durham - Pf eiff er - Gruber phenomenon, 
278 

Dust-cells, 585 
Dust-corpuscles, 436 
Dust-embolism, 69 
Dwarf tapeworm, 405 
Dwarfism, 884 
Dyscoria, 1022 

Dyscrasia, constitutional, 165 

tumor, 230 
Dysentery, 311, 669, 670 

amebic, 670 

bacillary, 670 

bacillus of, 311 
Dysmenorrhea membranacea, 816 
Dystrophy, 915 

Ear, 1033 

anatomy of, 1033 
congenital defects of, 1034 
external, 1034 

frost-bite of, 1034 

inflammations of, 1034 

mycosis of, 1035 



1074 



INDEX 



Ear, external, syphilis of, 1035 

tuberculosis of, 1034 

tumors of, 1035 
circulatory disturbances of, 1038 

inflammations of, 1038 
middle, 1036 

cholesteatoma of, 1038 

hemorrhage of, 1036 

inflammation of, 1036 

hyperemia of, 1036 

syphilis of, 1038 

tuberculosis of, 1038 

tumors of, 1038 
Ecchondroma, 183 
Ecchondroses, 183 
Ecchymosis, 68 

Echinococcus altricipariens, 409 

cysts, 407 

of peritoneal cavity, 733 
of testicles, 869 
seats, 410 

granulosus, 406 

hominis, 409 

multilocularis, 409 

scolicipariens, 408 

veterinorum, 408 
Echinorhynchus gigas, 420 
Ectatic aneurysm, 538 
Ecthyma, 1046 
Ectoplasm, 256 
Eczema, 1047 
Edema, 78 

alterations in blood as cause, 80 
of liquids of tissues as cause, 80 

angioneurotic, 80 

decreased tissue elasticity as cause, 79 

definition of, 78 

diffusion in, 79 

direct filtration in, 79 

etiology of, 78 

gaseous, 330. See also Emphysema, 
infections. 

increase of blood-pressure as cause, 79 
increased permeability of capillary 

walls as cause, 80 
inflammatory, 129 

malignant, 328. See also Malignant 
edema. 

obstruction of lymphatic circulation as 

cause, 80 
of brain, 953 
of cells, 100 
of conjunctiva, 1014 
of eyelids, 1032 
of kidneys, 755 
of larynx, 552, 553 
of lungs, 564 

of mucosa of intestines, 662 

of nasal cavities, 549 

of nerves, 1006 

of pharynx, 631 

of pia-arachnoid, 924 

of placenta, 856 

of skin, 1045 

of vulva, 852 

osmosis in, 79 

pathological anatomy, 81 

Quincke's, 1045 

results of, 81 



Edematous inflammation, 134 

laryngitis, 553 
e-granules, 434 

Ehrlich's side-chain theorv of immunitv, 
| 275 
Eimeria hominis, 395 
Elbow, miner's, 911 

Electrical currents, effect of, on bacteria, 
258 

influences in etiologv of disease, 31 
Eleidin, 1040 
Elephantiasis, 419, 1043 

congenita mollis, 187 

graecorum, 343 

of clitoris, 851 

of labise, 851 

of scrotum, 861 

of vulvae, 854 
Emboli, 68 

sources and nature, 69 
Embolism, 68 

air-, 69 

dust-, 69 

fat-, 69 

infections, 73 

of arteries, 912 

of brain, 957 

of coronary arteiy, 489 

of lungs, 567 

of mesenteric arteries, 662 
of portal vein, 688 
of renal arteries, 755 
of spermatic artery, 863 
of splenic artery, 461 
paradoxical, 70 
results of, 70 
retrograde, 69 
seats of, 69 
Embryomata, 247 
Embrj^onic rests, 166 
Emigration of leukocytes, 65 

theory of inflammation, 122 
Emphysema, infections, 330 
bacillus of, 330 
definition of, 330 
etiology of, 330 
pathological anatomy, 330 
of lungs, 567 
atrophic, 570 
bullous, 569 
compensatory, 568 
interstitial, 567 
senile, 570 
substantial, 568 
vesicular, 568 
vicarious, 568 
Emphysematous vaginitis, 851 
Empyema, 589, 615 
of gall-bladder, 713 
of joints, 904 
Encephalitis, 959 

acute parenclrymatous, 960 
chronic, 963 
etiology, 960 
lethargica, 371 
pathological anatomy, 960 
primary acute hemorrhagic, 963 i 
simple acute focal, 960 
suppurative, 961 



INDEX 



1075 



Encephalocele, 938 
Encephaloid carcinoma, 240 
Encephalomalacia, 958 
End-arteries, 70 
Endarteritis, 525, 527 
chronica deformans, 529 
obliterans, 534 
productive, 527 
proliferans, 527 
Endemic disease, 40 
Endocarditis, 489 
acute, 489 

etiology of, 490 
lesions in other organs in, 493 
pathological anatomy, 491 
results of, 493 
changes in other organs in, 497 
chronic, 494 

changes in heart in, 496 
etiology of, 494 
malignant, 494 
pathological anatomy, 495 
diphtheritic, 492 
malignant, 492 
mural, 489 
mycotic, 492 

pathological physiology, 497 

recurrent, 494 

rheumatic, 491 

septic, 492 

subacute, 494 

ulcerative, 492 

verrucose, 491 
Endocardium, diseases of, 489 

inflammation of, 489 
Endocrine glands, diseases of, 734 

physiologic considerations, 734 
Endolysin, 131, 271 
Endometritis, 817 

acute catarrhal, 817 

chronic, 817 

decidualis, 857, 858 

exfoliativa, 816 

glandularis, 818 

interstitialis, 818 

of cervix, chronic, 819 
Endomyces albicans, 365 
Endophlebitis, 543 
Endoplasm, 256 

Endosalpingitis tuberculosa, 846 
Endosporium, 256 
Endothelial cancer, 211 
Endothelioma, 211 

of lungs, 606 

of lymphatic glands, 478 
vessels, 547 

of peritoneum, 732 

of pia-arachnoid, 931 

of pleura, 620 

of spleen, 466 

of testicles, 868 
Endotheliomatous cylindroma, 210 
Endotoxins, 259 
Enlargement, hypertrophic, 164 
Enophthalmos, 1031 
Enostoses of bones, 901 
Entamoeba buccalis, 384 

coli, 384 

histolytica, 382, 383, 384 



. Entamoeba histolytica, description, 
382 

distribution, 384 
encysted state, 383 
pathogenesis, 384 

tetragena, 383 

urinalis, 384 
Enteritis, 663 

catarrhal, 664 

chronic, 665 

croupous, 664 

etiology, 663 

follicular, 664 

pathological anatomy, 663 
physiology, 665 

pseudomembranous, 664 

suppurative, 664 

toxic, 664 

ulcerative, 664 
Enterocystoma, 657 
Enterogenic albumosuria, 802 
Enteromycosis, 680 
Enterorrhagia, 68 
Enzymes, 260 
Eosinophile granules, 433 
Eosinophiles, 432 
Eosinophilia, 443 
Ependymitis of ventricles, 973 
Epicanthus, 1013 

Epidemic cerebrospinal meningitis, 927 

disease, 40 
Epidermis, 1040 
Epidermoid carcinoma, 238 
Epididymitis, 863 
acute, 808, 864 
Epigenesis, 22 
Epiglottis, cysts of, 555 
Epiphysis cerebri, 751. See also Pineal 

gland. 
Episcleritis, 1021 
Epispadias, 859 
Epistaxis, 68, 549 
Epithelial cysts, 244 
appearance, 244 
definition, 244 
etiology, 244 
nature of, 245 
seats of, 245 
structure of, 245 
perles, 237 
tumors, 223 

destructive, of placental site, 250 
of lung, 607 
of skin, 1056 
of stomach, 651 
Epithelioid cells, 147 
Epithelioma, 236 

basocellular, of skin, 1057 
benign cystic, of skin, 1057 
contagiosum, 396 
cylindrical, 240 
cystic, 238 
of penis, 861 
of scrotum, 861 
of skin, 1056 
squamous, 236 
of skin, 1057 
Epithelium, regeneration of, 157 
Epulis, 206, 629, 630 



1076 

Ergot, action of, 36 
Erosions of uterus, 820 
Erysipelas, 1053 
Erysipeloid vaginitis, 851 
Erythema, 1045 

multiform, 1045 
Erythrasma, 1055 
Erythroblast, 436 

primary, 480 

primitive, 435 
Erythrocytes, 429 

alterations of isotonicity, 438 

basic granulation, 437 

diapedesis of, in inflammation, 127 

karyokinetic figures in, 437 

nucleated, 436 

pathological changes in, 436 

pigmentation of, 437 

shape of, 436 

size of, 436 

skeined, 431 

vacuolation of, 437 

visible ameboid movements, 436 
Erythrocytosis, 442 
Escharotics, action of, 34 
Esophagitis, catarrhal, 638 
chronic, 638 

phlegmonous, 638 

pseudomembranous, 638 

ulcerative, 638 
Esophagus, anemia of, 638 

carcinoma of, 640 

congenital defects of, 637 

dilatation of, 639 

diverticula of, 639 

hyperemia of, 638 

inflammation of, 638. See also Eso- 
phagitis. 

passive congestion of, 638 

perforation of, 640 

rupture of, 640 

stenosis of, 639 

syphilis of, 640 

tuberculosis of, 640 

tumors of, 640 

typhoid ulceration of, 640 
Essential hematuria, 755 
Esthiomene, 853 
Etat crible, 959 
Etat segmentate, 504 
Etiology, definition of, 17 

of disease, 19 
Eumycetes, 254 
Eunuchism, 861 

Eustachian tube, inflammation of, 
1038 

Eustrongylus gigas, 420 
Exfoliative vaginitis, 850 
Exophthalmos, 1031 
Exosporium, 256 
Exostoses, 186 

of bones, 901 
Experimental acidosis, 45 
Exstrophy of bladder, 791 
External hydrocephalus, 924, 959 

pachymeningitis, suppurative, 921 
Extrapial hemorrhage, 924 
Extrasystoles, ventricular, 506 
Extra-uterine pregnancy, 847 



INDEX 

Extra-uterine pregnancy, etiology, 847 
pathological anatomy, 848 
varieties, 848 
Exudation in inflammation, 125 
of fluids in inflammation, 129 
Exudative inflammation, 134 
Eye, anatomy, 1012 

anterior chamber of, 1020 
congenital abnormalities, 1013 
cysts of, 1018 
tumors of, 1018 
Eyelids, 1032 
edema of, 1032 
inflammation of, 1032 
ptosis of, 1032 

congenital, 1013 
tumors of, 1032 

Facultative bacteria, 258 
Fallopian tubes, anatomy of, 841 
carcinoma of, 847 
changes of position, 841 
congenital abnormalities, 841 
cysts of, 847 
development of, 841 
dilatation of, 842 
fibroma of, 846 
fibromyoma of, 846 
hematoma of, 842 
hemorrhages into, 842 
hyperemia of, 842 
inflammations of, 842 
lipoma of, 846 

papillomatous elevations of, 846 
sarcoma of, 847 
stenosis of, 841 
syncytioma malignum of, 847 
syphilis of, 846 
tuberculosis of, 846 
tumors of, 846 
False aneurysm, 536, 542 
croup, 552 
neuroma, 218, 219 
syringomyelia, 987 
Familial gout, 21 
Farcy, 323 
buds, 323 
Fasciola hepatica, 398 
Fasciolopsis buskii, 401 

rathouisi, 401 
Fat crystals in urine, 806 
metabolism of, 42 
necrosis, 117 
Fat-embolism, 69 
Fat-splitting ferments, 261 
Fatty degeneration, 88 . 
definition, 88 
etiology, 89 

microscopic appearances, 89 
of arteries, 524 
of heart, 502 
of kidneys, 777 
of liver, 671 
of muscles, 918 
of prostate, 870 
of stomach, 649 
of suprarenal bodies, 745 
of testicles, 862 
of uterus, 824 



Fatty degeneration of veins, 542 
pathological anatomy, 89 

physiology, 90 
seats, 90 
infiltration, 86, 91 
definition, 86 
etiology, 86 
of bone-marrow, 481 
of dura mater, 978 
of heart, 501 
of kidney, 777 
of liver, 691 

of lymphatic glands, 469 
of mammary glands, 877 
of muscles, 918 
pathological anatomy, 87 

physiology, 88 
seats, 88 

necrosis of pancreas, 719 
Favus, 367, 1054 
Febris undulans, 321 
Fecal stones, 105 
Femoral hernia, 658 
Ferment, fibrin, 74 

glycolytic, 52 

theory of immunity, 272 

thrombosis, 74 
Fermentation, 260 
Ferments, 260, 268 

coagulating, 261 

diastatic, 260 

effects of, 261 

fat-splitting, 261 

formed, 260 

hydrolytic, 261 

inverting, 260 

living, 260 

nitrifying, 261 

of bacteria, 260 

oxidizing, 261 

proteolytic, 260 

unformed, 260 
Fetal adenoma, 738 

hydrocephalus, 938 

membranes, hemorrhages from, 856 
Fetid bronchitis, 557 
Fetus in fetu, 247, 251 
Fever, 55 

conservative effects, 57 

definition of, 55 

etiology of, 56 

nature of, 56 

paratyphoid, 677 

pathological anatomy, 57 
physiology, 57 

typhoid, 672 
Fibrse proprise, 934 
Fibrils, fibrogha, 176 
Fibrin-ferment, 74 
Fibrinogen, 74 
Fibrinoid, 114 

Fibrinopurulent inflammation, 135 
Fibrinous arthritis, 904 

bronchitis, 558 

inflammation, 135, 136 

pericarditis, 520 

pleuritis, 614 

pneumonia, 294, 572, 573. See a 
Croupous pneumonia. 



INDEX 1077 

! Fibrinuria, 802 

Fibro-adenoma of mammary glands, 877 
i Fibroblasts, 132, 158 
: Fibroglia fibrils, 176 
Fibroid phthisis, 594, 599 

tumor, recurrent, 201 
Fibroids, 221 

of uterus, 824 
Fibroma, 176 

appearance of, 177 

definition of, 176 

etiology of, 176 

intracanalicular, 178 

of mammary glands, 888 

mammae nodulum, 178 

nature of, 179 

of bladder, 799 

of bones, 901 

of brain, 971 

of Fallopian tubes, 846 

of heart, 518 

of kidneys, 780 

of larynx, 554 

of lungs, 606 

of mammary glands, 877 

of nerve sheaths, 178 

of peritoneum, 732 

of pleura, 619 

of skin, 1056 

of spleen, 466 

of testicles, 867 

of vagina, 852 

of vulva, 854 

seats of, 178 

secondary changes in, 179 

structure of, 178 
Fibromyoma, 219 

of Fallopian tubes, 846 
Fibromyxoma of vulva, 854 
Fibrosarcoma, 202 
: Fibrosis, art erio capillary, 529 

general, 145 
Fibrous connective tissue, regeneration 
of, 158 

goiter, 737 

osteitis, 893 

phthisis, 594 

pneumonia, 572, 577, 584 
Filaria bancrofti, 418 
bronchialis, 420 
conjunctivae, 420 
demarquayi, 420 
diurna, 420 
hominis oris, 420 
immitis, 420 
labialis, 420 
lentis, 420 
loa, 420 

lymphatica, 420 
medinensis, 417 
nocturna, 420 
ozzardi, 420 
perstans, 420 
restiformis, 420 
romanorum-orientalis, 420 
sanguinis hominis, 418 
varieties of, 420 
so Filariasis, 419 

Filterable viruses, 369 



1078 

Finkler and Prior, spirillum of, 350 
Fissure of anus, 665 
Fistulse of vagina, 850 

salivary, 637 
Fixateur, 268 
Flagella, 256, 385 
amphitrichous, 257 
lophotrichous, 257 
monotrichous, 257 
peritrichous, 257 
Fleshy moles, 856 
Fluke-worms, 397 
Focal glomerulonephritis, 767 
infection, 267 
necroses, 118 
Follicular conjunctivitis, 1015 
cysts of ovaries, 836 
enteritis, 664 
tonsillitis, 633 
Food, 41 

diminished supply, 41 . 
increased supply, 42 
transmission of disease, 425 
Foot, perforating ulcer, 140 
Foot-and-mouth disease, 379, 623 
Foreign bodies, cysts due to, 244 
in bladder, 795 
in blood, 457 
in bronchi, 561 
in intestines, 685 
in larynx, 555 
in nasal cavities, 551 
Foreign body giant cell in inflammation, 
132 

tubercle, 149 
Formative cells, 158 
Fowl-tuberculosis, 343 
Fracture, comminuted, 887 

compound, 887 

definition, 887 

repair of, 887 

ununited, 888 
Fragilitas ossium, 895 
Frambesia, 358 
Freezing, 29 

Friedberger's theory of infection, 284 
Friedlander's bacillus, 347 

pneumobacillus, 297 
Friedreich's ataxia, 996 
Fuchsin bodies, Russell's, 93, 113 
Fulminating infection, 266 
Fungi, cleft, 253 

true, 254 
Fungus, benign, of testicles, 864 

ray, 360 

syphilitic, of testicles, 867 

thrush, 365 
Furuncles, 140, 1052 
Fusiform bronchiectasis, 560 

Galactocele, 882 
Galactorrhea, - 877 

Galen's definition of inflammation, 122 
Gall-bladder, contraction of, 714 

dilatation of, 714 

dropsy of, 714 

empyema of, 713 

inflammation of, 713. See also Chole- 
cystitis. 



INDEX 

Galloping consumption, 594 
Gall-stones, 714 
etiology, 714 

pathological anatomy, 715 
structure of, 715 
Galton's law, 23 
Gametocytes, 391 

Ganglia, intracardiac, degeneration of, 
505 

of spinal nerves, diseases of, 1006 
of tendon-sheaths, 911 
spinal, diseases of, 1006 
Ganglionar neuroglioma, 970 
Ganglioneuroma, 217, 218 
Gangrene, 110, 118, 1043 
circumscribed, 118 
definition of, 118 
dry, 118 

foudroyante, 328 
gaseous, 328 
metastatic, 118 
moist, 118 
of lung, 590 
of vulva, 854 
primary, 118 
progressive, 118 
secondary, 118 
traumatic, 328 
Gangrenous inflammation, 142 

stomatitis, 625 
Gaseous edema, 330. See also Emphy- 
sema, infectious.' 
gangrene, 328 
Gastrectasia, 650 
Gastric ulcer, 646 
etiology, 646 

pathological anatomy, 646 
Gastritis, acute, 642 
atrophic, 644 
chronic, 643 
hypertrophic, 644 
interstitial, 645 
pathological anatomy, 643 
I physiology of, 645 
pseudomembranous, 643 
ulcerative, 643 
! Gastrodiscus hominis, 401 

Gastro-intestinal tract, diseases of, 622 
! Gastromalacia, 650 
Gastroptosis, 650 
Gaucher's splenomegaly, 464 
Gelatinous carcinoma, 242 
Genu valgum, 903 

varum, 903 
Geographical tongue, 365, 623 
Germinal cells, 932 
; Giant growth, 164 
of bones, 888 
Giant-cell, foreign body, in inflammation 
132 

sarcoma, 205 
Giant-cells in inflammation, 129 
Langhans', 148 
parenchymatous, 132 
Gibraltar fever, 321 
Gigantism, 164 
Gin-drinker's liver, 697 
Gingivitis, spirochetal, 624 
Glanders, 154, 322 



Glanders, definition of, 322 
etiology of, 322 
of larynx, 554 
of lungs, 605 
of muscles, 919 
of skin, 1054 

pathological anatomy, 323 
physiology, 323 
Glandular carcinoma, 240 

cystomata of ovaries, 836 

organs, regeneration of, 160 
Glaucoma, 1029 
Gleet, 809 
Glioma, 213 

appearance of, 213 

definition of, 213 

etiology of, 213 

ganglionare, 217 

nature of, 215 

of brain, 969 

of retina, 215 

of spinal cord, 1005 

of suprarenal bodies, 747 

seats of, 214 

structure of, 214 
Gliomatosis, 213 
Gliosis, 213 

hypertrophic nodular, 938 
Globular thrombi, 488 
Glomerular nephritis, sclerosis secondary 

to, 771 
Glomerulonephritis, 763 

focal, 767 

functional pathology of, 766 
Glossina morsitans, 388 

palpalis, 388 
Glossiolabiolaryngeal palsy, 1000 
Glossitis, 622, 626 

hemilateral, 626 

parenchymatous, 626 
Glucosuria, 800 

alimentary, 51 

clinical causes, 51 

due to excessive hepatic glycolysis, 51 
general scheme of possible causes, 51 
phloridzin, 53 
renal, 53 
Glycogenic infiltration, 100 
definition, 100 
etiology, 100 
of kidneys, 778 
pathological anatomy, 100 
physiology, 100 
reaction, 438 
Glycolysis, hepatic, excessive, glucosuria 

due to, 51 
Glycolytic ferment, 52 
Glycosuria, 20 
Goiter, adenomatous, 738 
coUoid, 737 
cystic, 737 
definition, 736 
etiology, 736 
fibrous, 737 

mechanical effects of, 740 
parenchymatous, 736 
pathological anatomy, 736 
secondary changes in, 740 
substernal, 736 



INDEX 1079 

Goiter, vascular, 737 
Gonococcus, 292 
cultivation of, 293 
pathogenicity of, 293 
Gonorrhea, 292, 807 
definition of, 292 
etiology of, 292 
pathological anatomy, 293 
physiology, 293 
Gonorrheal arthritis, 808 
tenosynovitis, 808 
urethritis, 810 
Gout, 49 

etiology of, 49 
familial, 21 
pathogenesis of, 49 
pathological anatomy, 49 
Gouty arthritis, 908 

conditions associated with, 909 
paroxysm, 908 
tophi, 49, 909 
Granddaughter-cysts, 409 
Granular disintegration, 86 
Granulation, 143 
healing by, 144 
tissue in inflammation, 132 
Granules, Altmann's, 85 
Babes-Ernst, 256 
of leukocytes, 433 
polar, 256 
sulphur, 361 
Granuloma, coccidioidal, 1055 
fungoides, 208 
infectious, 147 
malignum, 193 
pyogenicum, 367 
Graves' disease, 738, 743 
Ground itch, 414, 415 
Gruber-Durham phenomenon in typhoid 
fever, 307 

Gruber-Pfeiffer-Durham phenomenon, 
278 

Gruber-Widal reaction, 272 
Guinea-worm, 417 
Gumma, 1054 
of brain, 969 
of bones, 900 
of syphilis, 152, 354, 355 
syphilitic, of lungs, 604 
Gummy tumor, 355 
[ Gymnobacteria, 257 

Habitation in disease, 20 
Hsemoproteus danilewskyi, 394 
Hair, 1059 
; Hair-follicles, inflammation of, 1050 
; Halteridium danilewskyi, 394 
| Hamartoma, 187 
Hanot's cirrhosis, 701, 702 
Hansemann's theory of tumors, 167 
Haptophore, 268 

groups, 275 
Harelip, 622 

Hauser's theory of tumors, 167 

Adami's modification, 167 
Healing by first intention, 143 
by granulations, 144 
by immediate union, 143 
by second intention, 144 



1080 

Heart, 484 

abnormality in size, 485 
of position, 485 

abscess of, 507 

actinomycosis of, 518 

amyloid infiltration, 501 

anatomical considerations, 484 

aneurysm of, 516 

atrophy of, 513 

bilocular, 485 

block, partial, 506 

changes in, in chronic endocarditis, 

cloudy swelling, 500 

congenital diseases, 485 

defective development, 485 

deformities of, 485 

development of, 484 

dilatation of, 514 

fatty degeneration, 502 
infiltration, 501 

fibroma of, 518 

hyaline degeneration, 501 

hypertrophy of, 514 

hypoplasia of, 485, 512 

infectious diseases, 518 

lipoma of, 518 

myoma of, 518 

overaction of, 61 

pacemaker of, 505 

parasites of, 518 

pathological physiology, 487 

rhabdomyoma of, 518 

rupture of, 518 

sarcoma of, 518 

syphilis of, 518 

thrombosis of cavities, 487 

trilocular, 485 

tuberculosis of, 518 

tumors of, 518 

valvular defects, 487 

vitreous degeneration, 501 

weak, 60 

wounds of, 518 
Heart-failure cells, 564 
Heart-muscle, anemia of, 500 

hemorrhage in, 500 

hyperemia of, 500 

inflammation of, 506. See also Myo- 
carditis. 

parenchymatous degeneration, 500 

pathological physiology, 505 

segmentation of fibers, 504 
Heat, effect of, on bacteria, 258 

in etiology of disease, 27 
Heberden's nodes, 908 
Hemachromatosis, 690 
Hemangioma, 189 

appearance of, 189 

definition of, 189 

etiology of, 189 

nature of, 191 

seats of, 189 

structure of, 189 
Hematemesis, 68 
Hematochyluria, 419, 804 
Hematocolpos, 850 
Hematogenic albumosuria, 802 

purulent pneumonia, 588 

tuberculosis, 591, 600 



INDEX 

Hematogenous jaundice, 442, 717, 718 
pigmentation, 106 

microscopic appearance, 108 
purulent myelitis, 988 
Hematoidin, 921 

in urine, 806 
Hematoma, 68, 542 
auris, 1034 

of Fallopian tubes, 842 
of vulva, 853 
perirenal, 755 
496 Hematometra, 815, 850 
Hematomyelia, 983, 987 
Hematosalpinx, 845 
Hematuria, 803 
essential, 755 
Hemianopsia, 956 
Hemicrania, 937 
Hemilateral glossitis, 626 
Hemochromatosis, 107, 661 
Hemocytolysis, 441 
Hemoglobin in urine, 806 
Hemoglobinemia, 441 
Hemoglobinuria, 442, 803 

paroxysmal, 803 
Hemokonise, 436 
Hemolymph glands, 468 
Hemolysis, 118, 441 
Hemolytic ictero-anemia, 453 
Hemopericardium, 519 
Hemophilia, 67 
Hemoptysis, 68 
Hemorrhage, 65 
arterial, 65 
by contrecoup, 967 
capillary, 65 
causes of, 66 
cerebral, 954 
massive, 954 

pathological physiology, 956 
punctate, 954 

secondary degeneration after, 956 
classification of, 68 
diseases of blood-vessels causing, 66 
extrapial, 924 
from bones, 889 
from dura mater, 920 
from fetal membranes, 856 
from intestine, 68 
from lungs, 68 
from mammary glands, 875 
from muscles, 912 
from ovary, 834 
from pia-arachnoid, 924 
from stomach, 68 
from uterus, 816 
in chorioid, 1025 
in heart-muscle, 500 
in shell shock, 954 
in spleen, 461 

increase of blood-pressure as cause, 66 
into choroid plexus, 972 
into Fallopian tubes, 842 
into joints, 904 
into skm, 1044 
into vagina, 850 
into vitreous humor, 1022 
intrapial, 924 
leukocytosis from, 444 



Hemorrhage, neuropathic, 67 

of bladder, 793 

of brain, 954 

of bronchi, 556 

of conjunctiva, 1014 

of dura mater, 978 

of intestines, 662 

of kidneys, 755 

of larynx, 552 

of lungs, 565 

of middle ear, 1036 

of mouth, 622 

of nasal cavities, 549 

of nerves, 1006 

of pancreas, 718 

of pericardium, 519 

of peritoneum, 725 

of pharynx, 631 

of pia-arachnoid, 979 

of retina, 1027 

of spinal cord, 986 

of stomach, 641 

of suprarenal bodies, 746 

of tympanic membrane, 1035 

parenchymatous, 65 

per diabrosin, 66 

per diapedesin, 65 

per rhexin, 65 

petechial, of pleura, 610 

results of, 68 

shock from, 25 

traumatic, 66 

venous, 65 
Hemorrhagic diathesis, 67 

diseases, 367 

encephalitis, primary acute, 963 
infarct, 68, 71 

of lungs, 565 
inflammation, 140 
myositis, 913 

pachymeningitis, internal, 921, 978 

pancreatitis, acute, 720 

pericarditis, 521 

pleuritis, 616 

vaginitis testis, 865 
Hemorrhoids, 662 

etiology of, 662 

pathological anatomy, 663 
Hemosiderosis, 702 

of liver, 110 
Hemosporidia, 389 
Hemothorax, 611 

Hepatic glycolysis, excessive, glucosuria 

due to, 51 
Hepatitis, 694 

interstitial, acute, 695 
chronic, 696 

parenchymatous, 694 
Hepatogenous jaundice, 717 

pigmentation, 108 
Hereditary congenital pathological con- 
ditions, 22 
Heredity in carcinoma, 231 

in etiology of disease, 21. See also 
Inheritance. 
Hermaphroditism, 251, 859 
Hernia, diaphragmatic, 650 

etiology of, 657 

external, 658 



INDEX 1081 

I Hernia, internal, 658 
of intestine, 657 
pathological anatomy, 658 
I strangulated, 659 
I Herpes, 1047 
I labialis, 623 
I Herpetic angina, 631 
laryngitis, 552 
Herzfehlerzellen, 564 
Heterochromia, 1023 
Heteroplastic osteoma, 186 
Heterotopia of gray matter of cord, 983 
Hidden carriers, 426 
Hippuric acid in urine, 806 
Hirschsprung's disease, 656 
Hirudo ceylonica, 421 

vorax, 421 
His, bundle of, 484 
Histoplasma capsulatum, 389 
Histoplasmosis, 389 
Hives, 1045 
Hob-nail liver, 698 
Hodgkin's disease, 193, 457 
of lymphatic glands, 477 
spleen in, 465 
Hookworm, 413 
Hordeolum, 1032 
Hormone, 163, 734 
Horseshoe-kidney, 753 
Housemaid's knee, 911 
Howell-Jolly bodies, 437 
Howship's lacunae, 892 
Human transmission of disease, 426 
Huntingdon's chorea, 964 
Hutchinson's teeth, 356, 629 
Hyaline change, Zenker's, 306 
degeneration, 92 
definition, 92 
etiology, 92 
of arteries, 525 
of brain, 950 
of heart, 501 
of lymphatic glands, 470 
of muscles, 918 
of spinal cord, 986 
of spleen, 465 
pathological anatomy, 93 

physiology, 94 
seats, 94 
thrombi, 78, 93 
Zenker's, 94 
Hyaloserositis, 730 
Hydatid cysts, 409 

moles, 848, 858 
Hydatids of Morgagni, 847 
Hydradenitis, 1058 
Hydremia, 440 

Hydrocele funiculi cystica, 865 
spermatici, 865 
of testicles, 865 
processus vaginalis, 865 
spermatica, 865 
Hydrocephalus, 975 
acute, 929 

acquired, internal, 977 
acquired, 977 
chronic, 977 
external, 924, 959, 977 
fetal, 938 



1082 



INDEX 



Hydrocephalus interims, congenital, 976 

partial, 977 
Hydrolytic ferments, 261 
Hydroma durae matris, 921 
Hydrometra, 815 
Hydromnios, 856 
Hydromyelia, 983 
Hydronephrosis, 786 
Hydropericardium, 519 

chylous, 519 
Hydrophobia, 375 
Hydrops articulorum, 905 

ex vacuo, 925, 959 

omenti, 727 
Hydrorrhachus, 983 

externa, 983 
Hydrorrhcea gravidarum, 856 
Hydrosalpinx, 845 
Hydrothionuria, 801 
Hydrothorax, 611 
Hygroma, 924 

congenital cystic, 188 
Hymenolepis diminuta, 406 

nana, 403, 405 
Hyperchromatosis, 112 
Hyperemia, active, 63 
of pleura, 610 

arterial, 63 

collateral, 63 
of lungs, 562 

local, 63 

neuroparalytic, 63 

neurotonic, 63 

of bladder, 793 

of bones, 889 

of brain, 952 

of bronchi, 556 

of conjunctiva, 1013 

of dura mater, 920 

of esophagus, 638 

of Fallopian tubes, 842 

of heart-muscle, 500 

of intestines, 662 

of joints, 903 

of kidneys, 754 

of larynx, 552 

of liver, 687 

of lungs, 562, 563 

of mammary glands, 875 

of middle ear, 1036 

of mouth, 622 

of muscles, 912 

of nasal cavities, 549 

of nerves, 1006 

of optic nerve, 1030 

of ovaries, 834 

of pancreas, 718 

of pericardium, 519 

of peritoneum, 725 

of pharynx, 631 

of pia-arachnoid, 924, 979 

of retina, 1026 

of skin, 1044 

of spinal cord, 986 

of spleen, 460 

of stomach, 641 

of testicles, 863 

of thyroid gland, 735 

of uterus, 815, 816 



Hyperemia of uveal tract, 1023 

of vagina, 850 

of vulva, 852 

passive, 63 
of pleura, 610 

venous, 63 
Hyperglucemia, 50 
Hyperidrosis, 1058 
Hyperinosis of blood-plasma, 439 
Hypernephroma, 745 

of kidneys, 780 

of suprarenal bodies, 747 
Hyperplasia, 82, 164, 776 

chronic, of spleen, 463 

of deciduse, 858 

of mucous membrane of uterus, 824 
Hyperplastic perihepatitis, 730 
Hypersecretion of cerebro-spinal fluid, 

972 

Hypersusceptibility, 282 
Hyperthyroidism, 740, 743 
Hypertonicity of blood-serum, 439 
Hypertrichosis, 1059 
Hypertrophic enlargement, 164 

gastritis, 644 

nodular gliosis, 938 

osteo-arthropathy, 890 

rhinitis, 550 
Hypertrophy, 163 

definition of, 163 

etiology of, 163 

numerical, 164 

of arteries, 524 

of bone, 888 

of bone-marrow, 481 

of brain, 938 

of cervix uteri, 824 

of heart, 514 

of kidneys, 776 

of liver, 703 

of lungs, 567 

of lymphatic glands, 468 

of mammary glands, 876 

of muscles, 912 

of pituitary body, 749 

of prostate, 870 
results, 873 

of skin, 1041 

of testicle; 862 

of tonsils, chronic, 633 

of uterus, 824 

pathological anatomy, 164 
physiology, 164 

simple, 164 

true, 164 
Hyphomycetes, 343 
Hypinosis of blood-plasma, 439 
Hypophysis cerebri, 748. See also Pitui- 
tary body. 
Hypoplasia of arteries, 524 

of bones, 895 

of brain, 939 

of cerebellum, 939 

of cerebral hemispheres, 939 

of heart, 485, 512 
Hypopyon, 1019, 1023 
Hypospadias, 859 
Hypostatic congestion, 60, 63 

pneumonia, 578, 581 



INDEX 



1083 



Ichthyosis, 1042 
Ictero-anemia, hemolytic, 453 
Icterus, 717. See also Jaundice. 

seu febris amantium, 449 
Idiosyncrasy in disease, 20 
Ileum, inflammation of, 666 
Immune body, 268, 279 

chemistry, 285 
Immunity, 19, 268 

acquired, 268 
bacterial, 268 
toxin, 269, 273 

active acquired, 269 

alexin theory, 269 

antibacterial, 281 

antitoxic, 281 

bacterial, 277 

agglutination theory, 272 
alexin theory, 269 
as applied to bacteriolysis, 278 
to cytolysis, 278 

bacteriolytic theory, 270 

definition of, 268 

Ehrlich's side-chain theory, 275 

ferment theory, 272 

isopathic, 341 

Metschnikoff's theory, 270 

natural, 268 
bacterial, 268 
toxin, 268, 272 

opsonin theory, 271 

passive acquired, 269 

Pfeiffer's theory, 270 

phagocytosis theory, 270 

theories of, 269 

varieties of, 268 
Immunization, 268 
Impetigo, 1047 
Inanition, 41 
Indicanuria, 801 
Indigo in urine, 806 
Indolent ulcers, 140 
Induration, cyanotic, of spleen, 461 
Indurative pancreatitis, chronic, 721 
Infantile kala-azar, 388 

paralysis, 378, 975, 990 
Infantilism, 82 
Infarction, 70 
Infarcts, 70 

anemic, 71 

formation of, 71 

hemorrhagic, 68, 71 
of lungs, 565 

in uriniferous tubules, 779 

placental, 856 

pulmonary, 73 

subsequent changes in, 72 

uratic, 104 

white, 71 
Infected carrier, 426 
Infection, 264, 265 

acute, 267 

anaphylotoxin theory, 284 

atrium, 264 

chronic, 267 

contact, 424 

direct, 424 

focal, 267 

Friedberger's theory, 284 



Infection, fulminating, 266 
mixed, 267 
paracolon, 308 
paratyphoid, 308 
terminal, 267 
Infectious character of tumors, 167 
diseases, 39, 626 

general, 40 

local, 40 

of arteries, 535 

of bronchi, 561 

of heart, 518 

of larynx, 553 

of lung, 591 

of lymphatic glands, 472 

vessels, 547 
of nasal cavities, 550 
of pericardium, 522 
of pharynx, 634 
of pleura, 618 
of spleen, 466 
of trachea, 556 
of veins, 545 

whose cause is not certainly known, 
369 
embolism, 73 

emphysema, 330. See also Emphy- 
sema, infectious. 

granulomata, 147 

leukocytosis, 444 

theory of carcinoma, 230 
Infestation, 264 
Infiltration, 84 

albuminous, 84 

amyloid, 97. See also Amyloid infil- 
tration. 

calcareous, of arteries, 525 
of pia-arachnoid, 979 

dropsical, 100 
of liver, 694 

fatty, 86. See also Fatty infiltra- 
tion. 

glycogenic, 100. See also Glycogenic 

infiltration. 
purulent, 139 

round-cell, in inflammation, 131 
uratic, 104 
Inflammation, 121 
catarrhal, 141 

cellular and attraction theory, 122 
changes in blood-vessels in, 124 
chemical processes involved in, 130 
chronic, 143 

Cohnheim's emigration theory, 122 
consequences of, 121 
croupous, 136 
degeneration, 142 

degenerative changes in tissues in, 
133 

definition of, 121 

diapedesis of red corpuscles in, 127 
diphtheritic, 135, 136 
edematous, 134 
emigration theory, 122 
etiology, 134 
exudation in, 125 

of liquids in, .129 
exudative, 134 
fibrinopurulent, 135 



1084 

Inflammation, fibrinous, 135, 136 
foreign body giant-cell in, 132 
Galen's definition, 122 
gangrenous, 142 
giant-cells in, 129 
granulation tissue in, 132 
hemorrhagic, 140 
historical note on, 122 
influence of nervous system in, t25 
large mononuclear phagocytic cells in, 
128 

lymphadenitis, 470 
mucopurulent, 142 
necrotic, 142 

of arteries, 525. See also Arteritis. 
of biliary ducts, 711. See also Cho- ! 
langitis. 

of bladder, 793. See also Cystitis. 
of bone-marrow, 482 
of bones, 889. See also Periostitis. 
of brain substance, 959. See also 

Encephalitis. 
of bronchi, 557. See also Bronchitis. 
of bursse, 911 

of cavernous bodies of penis, 860 
of cecum, 666 

of choroid, 1025. See also Choroiditis. 

plexus, 972 
of ciliary body, 1024 
of conjunctiva, 1014. See also Con- , 

junctivitis. 
of corium, 1052 

of cornea, 1018. See also Keratitis. 

of dura mater, 921. See also Pachy- 
meningitis. 

of endocardium, 489. See also Endo- 
carditis. 

of esophagus, 638. See also Eso- 
phagilis. 

of Eustachian tube, 1038 

of external ear, 1034 

of eyelids, 1032 

of Fallopian tubes, 842 

of gall-bladder, 713. See also Chole- 
cystitis. 

of hair-follicles, 1050 

of heart-muscle, 506. See also Myo- 
carditis. 

of ileum, 666 

of internal ear, 1038 

of intestines, 663. See also Enteritis. 

of iris, 1023. See also Iritis. 

of joints, 904. See also Arthritis. 

of kidneys, 756. See also Nephritis. \ 

of lachrymal sac, 1018 

of larynx, 552. See also Laryngitis. 

of liver, 694. See also Hepatitis. 

of lungs, 572. See also Pneumonia. 

of lymphatic vessels, 546 

of mammary glands, 875. See also 
Mastitis. 

of middle ear, 1036. See also Otitis 
media. 

of mouth, 622. See also Stomatitis. 
of mucous membrane of glans penis, 
860 

of muscles, 913. See also Myositis. 
of nails, 1059 
of nasal cavities, 550 



INDEX 

Inflammation of nerves, 1008. See also 
Neuritis. 
of nipples, 875 

of optic nerve, 1030. See also Papil- 
litis. 
of ovaries, 834 

of pancreas, 720. See also Pancreatitis. 
of pelvis of kidney, 789. See also 
Pyelitis. 

of pericardium, 519. See also Peri- 
carditis. 

of peritoneum, 727. See also Peri- 
tonitis. 

of pharynx, 631. See also Pharyngitis. 
of pia-arachnoid, 925, 979. See also 

Leptomeningitis. 
of pituitary body, 749 
of placenta, 857 

of pleura, 612. See also Pleuritis. 
of prepuce of penis, 860 
of prostate, 869. See also Prostatitis. 
of pulp of teeth, 630 
of rectum, 669. See also Proctitis. 
of retina, 1027. See also Retinitis. 
of salivary glands, 636. See also 

Parotitis. 
of sclera, 1021 
of seminal vesicles, 874 
of sheaths of tendons, 911. See also 

Tenosynovitis. 
of skin, 1045 

of spinal cord, 988. See also Myelitis. 
of spleen, 461. See also Splenitis. 
of stomach mucosa, 642. See also 

Gastritis. 
of subcutis, 1052 
of suprarenal bodies, 747 
of sweat-glands, 1058 
of testicle, 863. See also Orchitis. 
of thoracic duct, 548 
of thymus gland, 748 
of thyroid gland, 736. See also 

Thyroiditis. 
of tongue, 622. See also Glossitis. 
of tonsils, 632. See also Tonsillitis. 
of trachea, 556 
of tympanic membrane, 1035 
of ureter, 790 

of urethra, 807. See also Urethritis. 
of uterus, 817 

of vagina, 850. See also Vaginitis. 
of vas deferens, 866 
of veins, 542. See also Phlebitis. 
of vitreous humor, 1022 
of vulva, 853 
parenchymatous, 134, 142 
pathological physiology, 145 
phenomena of, in vascular tissues, 122, 
123 

phlegmonous, 139 
plasma-cells m, 129 
productive, 134, 142 
proliferative changes in, 131 
pseudomembranous, 135, 136 
purulent, 142 

repair and, interpretation of, 133 
resolution after, 146 
role and fate of leukocytes in, 127 
round-cell infiltration in, 131 



INDEX 



1085 



Inflammation, secondary cellular degen- 
eration in, 133 
serofibrinous, 135 
serous, 134 
special forms, 134 
specific, 147 
suppurative, 137, 142 
symptoms of, 122 
types, 134 

vascular theories, 122 

Virchow's theory, 122 
Inflammatory edema, 129 

leukocytosis, 444 

osteoporosis, 892 
Influenza, 312 

bacillus of, 312 

organisms resembling, 317 
pathological lesions induced by, 313 

definition of, 312 

etiology of, 312 

pathological characters, 314 
Influenzal meningitis, 313 
Infractions of bones, 885 
Infusoria, 396 
Inguinal hernia, 658 
Inheritance, blended, 23 

collateral, 22 

cumulative, 24 

diathetic, 24 

direct, 21 

familial, 21, 23 

in etiology of ^disease, 21 

indirect, 21 

mosaic, 23 

particulate, 23 

racial, 21, 23 

reversionary, 23 
Insect venom, poisoning from, 37 

transmission of disease, 426 

with cycle of development in 
intermediate host, 427 
Intermediary body, 279 

callus, 888 
Intermediate body, 268 
Internal cephalohematoma, 920 

hemorrhagic pachymeningitis, 921 
Interstitial appendicitis, 668 

emphysema of lungs, 567 

gastritis, 645 

hepatitis, acute, 695 
chronic, 696 

keratitis, 1019 

nephritis, acute, sclerosis following, 771 
nonsuppurative nephritis, acute, 769 
pneumonia, 573 
pregnancy, 848 

suppurative nephritis, acute, 769 
Intestinal obstruction, 659 
Intestines, abnormalities of, 655 

actinomycosis of, 680 

amyloid infiltration of mucosa of, 661 

anthrax of, 680 

atrophy of mucosa of, 661 

carcinoma of, 682 

congenital abnormalities in position, 
656 

m enlargement of, 656 
dilatation of, 657 
diverticula of, 656 



Intestines, edema of mucosa of, 662 

foreign bodies in, 685 

hemorrhage from, 68, 662 

hernia of, 657 

hyperemia of, 662 

inflammation of, 663 

internal strangulation of, 659 

intussusception of, 660 

invagination of, 660 

narrowing of, 657 

obstruction of, 659 

parasites of, 684 

pigmentation of mucosa of, 661 

rupture of, 685 

sarcoma of, 680 

stenosis of, 657 

syphilis of, 679 

tuberculosis of, 678 

tumors of, 680 

volvulus of, 659 
Intoxicating dose of serum, 283 
Intoxication, 265 

in necrosis, 111 
Intracanalicular fibroma, 178 
of mammary glands, 878 

sarcoma, 879 
Intracardiac ganglia, degeneration of, 

505 

Intrapial hemorrhage, 924 

Intra-uterine transmission of tubercu- 
losis, 336 

Intussusception of intestines, 660 

Invagination of intestines, 660 

Invasion diseases, 40 

Inversion of uterus, 814 

Inverting ferments, 260 

Involucrum of bones, 891 

Involution forms of bacteria, 257 
of uterus, 83 

Iodophilia, 438 

Iriderenia, 1023 

Iridocyclitis, 1024 

Iris, 1013 

anemia of, 1023 
atrophy of, 1023 

congenital abnormalities of, 1022 

cysts of, 1024 

inflammations of, 1023 

syphilis of, 1024 

tuberculosis of, 1024 

tumors of, 1024 
Iritis, plastic, 1023 

purulent, 1023 

serous, 1023 
Irritation cells, 433 

external, as cause of tumors, 166 
Ischemia, 62 
Ischiopagi, 252 

Islands of Langerhans, diseases of, 719 
Isopathic immunity, 341 
Isospora bigemina, 395 
Itch, 1055 

coolie, 414, 415 

ground, 414, 415 
Ixodes bovis, 394 

Jaundice, 108, 717 
catarrhal, 666, 717 
etiology of, 717 



1086 



INDEX 



Jaundice, hematogenous, 442, 717, 718 

hepatogenous, 717 

pathological anatomy, 718 
Jobling's theory of anaphylaxis, 284 
Joint-mice, 911 
Joints, ankylosis of, 903 

diseases of, 903 

distortions of, 903 

dropsy of, 904 

empyema of, 904 

hemorrhage into, 904 

hyperemia of, 903 

inflammations of, 904 

luxation of, 903 

syphilis of, 911 

tuberculosis of, 909 
etiology, 909 

pathological anatomy, 909 
secondary disorders, 910 
tumors of, 911 

Kakke, 58 
Kala-azar, 388 

infantile, 388 
Karyokinesis, 156, 157 

asymmetric, 157 

multipolar, 157 

pathological, 157 
Karyokinetic figures, 437 
Karyolysis, 112 
Karyorrhexis, 112, 157 
Keith-Black node, 505 
Keloid, 1056 

false, 179 

true, 179 
Keratitis, 1018 

bullous, 1019 

interstitial, 1019 

phlyctenular, 1020 

suppurative, 102 

ulcerative, 1019 
Keratomalacia, 1020 
Keratosis, 1042 

Kidney, acquired malpositions of, 753 
adenoma of, 783 
amyloid infiltration of, 778 
anemia of, 754 
animal parasites in, 786 
atrophy of, 776 
bacteria in, 785 
calcification of, 777 
calculi in pelvis of, 788 
carcinoma of, 783 
changes of position of, 753 
congenital an malies, 753 

malposition of, 753 
cysts of, 784 
edema of, 755 

embolism of arteries of, 755 
fatty degeneration of, 777 

infiltration of, 777 
fibroma of, 780 
function of, 758 
glycogenic infiltration of, 778 
hemorrhage of, 755 
horseshoe, 753 
hyperemia of, 754 
hypernephroma of, 780 
hypertrophy of, 776 



Kidney, inflammation of, 756. See also 
Nephritis. 
large white, 762 
lipoma of, 780 
of pregnancy, 762 
parasites of, 785 

parenchymatous degeneration of, 776 
pelvis, inflammation of, 789. See also 
Pyelitis. 
malformations of, 786 
tuberculosis of, 790 
tumors of, 791 
sarcoma of, 782 
simple senile atrophy of, 776 
surgical, 769 
syphilis of, 780 
teratoma of, 780 
thrombosis of veins of, 755 
tuberculosis of, 779 
tumors of, 780 
secondary, 783 
Klebs-Loffler bacillus, 299 
Knee, housemaid's, 911 
Knock-knee, 903 
Kobelt's tubercles, cysts of, 840 
Koch's laws of specificity of bacteria, 39 
Koch- Weeks bacillus, 317 
Koplik's spots, 623 
Kraurosis vulvae, 851, 853 

Labile, elephantiasis of, 851 
Lacerated wounds of brain, 967 
Lachrymal organs r 1012, 1018 

sac, inflammation of, 1018 
Lactosuria, 800 
Lacunar tonsillitis, 633 
Laennec's cirrhosis, 697 
La grippe, 312 
Lambha intestinalis, 386 
Landry's ascending paralysis, 992 
Langerhans, islands of, diseases of, 719 
Langhans' cells, 855 

giant-cell, 148 
Lardacein, 97 
Lardaceous disease, 97 
Laryngitis, catarrhal, acute, 552 
chronic, 552 

croupous, 553 

diphtheritic, 553 

edematous, 553 

herpetic, 552 
Larynx, 551 

anatomical considerations, 551 

anemia of, 552 

atrophy of, 554 

carcinoma of, 555 

congenital abnormalities, 551 

edema of, 552, 553 

fibroma of, 554 

foreign bodies in, 555 

glanders of, 554 

hemorrhage of, 552 

hyperemia of, 552 

infectious diseases, 553 

inflammation of, 552. See also Laryn- 



leprosy of, 554 
lupus of, 554 
papilloma of, 554 



INDEX 



1087 



Larynx, parasites of, 555 

polyps of, 555 

stenosis of, 554 

syphilis of, 554 

tuberculosis of, 553 

tumors of, 554 
Lateral displacements of uterus, 813 
Laverania malariae, 389, 391 
Law, Galton's, 23 

Mendel's, 23 
Lead, action of, 35 
Leather-bottle stomach, 645 
Leiomyoma, 219 

appearance of, 220 

definition of, 219 

etiology of, 219 

nature of, 222 

of uterus, 824 

seats of, 220 

structure of, 220 
Leishmania donovani, 388 
Leishmaniosis, 388 
Lens, crystalline, 1021 

of eye, 1012. See also Crystalline lens. 
Lenticular cataract, 1021 

degeneration, 963 
Leontiasis leprosa, 345 

ossium, 893 
Lepra, 343 

cell, 154 

gangrenosa, 346 

mutilans, 346 

of bones, 901 

of testicles, 867 
Leproma, 153 
Leprosy, 153, 343, 1054 

anesthetic, 345 

bacillus of, 343 

definition of, 343 

etiology of, 343 

nodular, 345 

of cornea, 1020 

of larynx, 554 

of liver, 705 

of lymphatic glands, 476 
of nerves, 1010 
pathological anatomy, 345 

physiology, 346 
tubercular, 345 
Leptomeningitis, 925 
acute, 979 
chronic, 928, 980 
etiology, 925 

pathological anatomy, 925 
Leptospira icteroides, 369 
Leptothrix buccalis, 343 
Lethargic encephalitis, 371 
Leucin in urine, 806 
Leucosarcoma, 197 
Leukemia, 196, 453 

acute, 456 

aleukemic, 456 

blood in 455 

bone-marrow in, 482 

definition of, 453 

dermal, 454 

etiology of, 453 

lymphatic, 456 

bone-marrow in, 482 



Leukemia, myelogenous, bone-marrow 
in, 482 

myeloid, 455 

of lymphatic glands, 476 

pathological anatomy, 454 

spleen in, 465 
Leukemic stomatitis, 628 
Leukoblasts, 433 
Leukocytes, 431 

emigration of, 65 

granules of, 433 

large mononuclear, 431 

number of, 434 

pathological changes in, 438 

polymorphonuclear, 432 

polynuclear, 432 

proportions of different forms, 434 

role and fate, in inflammation, 127 

transitional, 432 
Leukocytic shadows, 438 
Leukocytoid cells, 158 
Leukocytosis, 443 

cachectic, 444 

character of blood in, 445 

etiology of, 443 

from hemorrhage, 444 

from malignant tumors, 444 

infectious, 444 

inflammatory, 444 

mechanical and thermal causes, 444 

medicinal, 444 

pathogenesis of, 444 

pathological physiology, 445 

polymorphonuclear, 443 
Leukolysis, 445 
Leukopenia, 445 
Leukoplakia, 623, 851 
Leukoprotease, 130 
Leukorrhea, 851 
Levulosuria, 800 
Leydenia gemmipara, 385 
Leydig, cells of, 861 
Lichen, 1050 

Light, effect of, on bacteria, 258 
Lime, oxalate of, in urine, 804 
Linguatula rhinaria, 421 
Linitis gastrica, 645 
Lipase. 117 
Lipemia, 441, 777, 803 
Lipoid metamorphoses, 91 
Lipoma, 181 

appearance of, 181 

definition of, 181 

etiology of, 181 

nature of, 182 

of bones, 901 

of Fallopian tubes, 846 

of heart, 518 

of kidneys, 780 

of lungs, 606 

of mammary glands, 878 

of peritoneum, 732 

of pia-arachnoid, 932 

of pleura, 619 

of skin, 1056 

of vulva, 854 

seats of, 182 

structure of, 182 
Lipomatosis, 181 



1088 

Lipomatosis of mammary glands, 877 
Liponeurofibroma, 219 
Lips, large, 622 
Lipuria, 803 

Liquefaction necrosis, 115 

definition, 115 

pathological anatomy, 115 
Liquids, exudation of, in inflammation, 
129 

Liquor sanguinis, 429, 435 
Lithopedia, 103 
Lithopedion, 849 
Liver, abscess of, 695 

pathological anatomy, 695 

actinomycosis of, 705 

acquired changes of form, 686 
of position of, 687 

acute yellow atrophy of, 691 

adenoma of, 707 

amyloid infiltration of, 693 

anatomical considerations, 685 

anemia of, 687 

angioma of, 706 

atrophy of, 689 

beer-drinker's, 701 

carcinoma of, 708 
secondary, 709 

cirrhosis of, 696 

congenital changes of position of, 686 

malformations of, 686 
cyanotic induration of, 688 
cysts of, 709 

dropsical infiltration of, 694 
fatty degeneration of, 691 

infiltration of, 691 
gin-drinker's, 697 

hemosiderosis of, 110 
hob-nail, 698 
hyperemia of, 687 
hypertrophy of, 703 
inflammation of, 694 
leprosy of, 705 
lymphadenomata of, 707 
morbid anatomy, 698 
necrosis of, 694 
nutmeg, 687 
parasites of, 710 

parenchymatous degeneration, 691 

pathological anatomy of, 693 

pigmentation of, 690 

red atrophy of, 687 

rupture of, 704 

sarcoma of, 707 

spots, 1043 

syphilis of, 704 

tuberculosis of, 704 

tumors of, 706 

yellow atrophy of, 691 
Liver-fluke, 398 
Lividity, postmortem, 61 
Livores mortis, 120 

Lobar pneumonia, 294, 573. See also 
Croupous pneumonia. 
sclerosis, 963 
Lobular pneumonia, 578 
Locomotor ataxia, 993 
Locus minoris resistentise, 25 
Lophotrichous flagella, 257 
Ludwig's angina, 632, 637 



INDEX 

Luetin reaction, 353 
Lungs, 561 
abscess of, 589 
absence of, 562 
actinomycosis of, 605 
adenoma of, 607 
anatomical considerations, 561 
anemia of, 562 
atrophy of, 567 
carcinoma of, 607 
carnification of, 572 
chondroma of, 606 
circulatory disturbances, 562 
congenital defects, 562 
congestion of, 562 
cyanotic induration, 564 
cysts of, 609 
edema of, 564 
embolism of, 567 
emphysema of, 567 
endothelioma of, 606 
epithelial tumors, 607 
fibroma of, 606 
gangrene of, 590 
glanders of, 605 
hemorrhage of, 68, 565 
hemorrhagic infarcts, 565 
hyperemia of, 562 

collateral, 562 
hypertrophy of, 567 
hypostatic congestion, 564 
infectious diseases, 591 
inflammation of, 572. See also 

Pneumonia. 
lipoma of, 606 
lymphadenoma of, 606 
lymphoma of, 606 
osteoma of, 606 
parasites of, 609 
sarcoma of, 606 
splenization of, 572 
syphilis of, 603 

syphilitic fibrous induration, 605 

gumma of, 604 
tuberculosis of, 591 
tumors of, 606 
Lupus, 1053 
carcinoma, 627 
erythematosus, 1050 
of larynx, 554 
of mouth, 627 
verrucosa, 1053 
Vulgaris, 340, 1053 
Lustgarten's bacillus, 351 
Luxation of crystalline lens, 1022 

of joints, 903 
Lymph, 79 

Lymphadenia, aleukemic, 477 

ossea, 902 
Lymphadenitis, acute, 470 
chronic, 471 
inflammation, 470 
scrofulous, 474 
suppurative, 471 
Lymphadenoma, 192 
of liver, 707 
of lungs, 606 
of lymphatic glands, 478 
Lymphadenosis, 477 



INDEX 



1089 



Lymphangiectasia, 546 
acquired, 546 
congenital, 546 
Lymphangioma, 187 
cavernous, 188 
cystic, 188 
of brain, 971 
of spleen, 466 
telangiectatic, 188 
Lymphangitis, 546 

purulent, 589 
Lymphatic circulation, obstruction of, as 
cause of edema, 80 
glands, 467 

actinomycosis of ? 476 
amyloid infiltration, 469 
anatomical considerations, 467 
atrophy of, 468 
calcification, 470 
carcinoma, 479 
degenerations of, 469 
endothelioma of, 478 
fatty infiltration, 469 
functions, 467 
Hodgkin's disease, 477 
hyaline degeneration, 470 
hypertrophy of, 468 
infectious diseases, 472 
leprosy, 476 
leukemia, 476 
lymphadenoma of, 478 
lymphoma of, 478 
lymphosarcoma of, 478 
necrosis, 470 
pigmentation, 470 
sarcoma, 479 
syphilis, 476 
tuberculosis, 472 

individual groups, 474 
tumors, 478 
leukemia, 456 • 
m bone-marrow in, 482 
tissues, diseases of, 459 
vessels, 545 

anatomical considerations, 545 
dilatation of, 546 
endothelioma, 547 
infectious diseases, 547 
inflammation of, 546 
parasites of, 547 
syphilis, 547 
tuberculosis, 547 
tumors, 547 
Lymphemia, 443 
Lymphoblastic cells, 468 
Lymphoblastoma, 192 
Lymphoblasts, 467 
Lymphocytes, 431 

large, 431 
Lymphodermia perniciosa, 454 
Lymphogenic tuberculosis, 591, 603 
Lymphogranuloma, 193 
Lymphoid tubercles, 147 
Lymphoma, 191, 468 
of lungs, 606 
of lymphatic glands, 478 
simple, 192 
Lymphoprotease, 131 
Lymphorrhea, 188, 854 
69 



Lymphosarcoma, 192, 204 
of lymphatic glands, 478 
Lymphosarcomatosis, 193 
Lyssophobia, .377 
Lytic action of serum, 271 

Macrocephaly, 938 
Macrocheilia, 188, 547, 622 
Macrogametocyte, 391 
Macroglossia, 188, 547, 622 
Macules, 1045 
Madura-foot, 363 
Mai de Caderas, 387 
Malakaplakia, 794 
Malaria, 389 

ague cake of, 464 

parasites of, 389 

pathological anatomy, 393 
physiology, 393 

relations of mosquitoes to, 392 
Malformations, congenital, of bronchi, 
556 

of pharynx, 630 

of tonsils, 630 
of trachea, 555 
Malignant adenoma, 228 

of uterus, 828 
edema, 328 

bacillus of, 329 

definition, 328 

etiology, 329 

pathological anatomy, 330 
physiology, 330 
endocarditis, 492 
pustule, 326, 1052 
Mallein, 323 
Malodorus sweat, 1058 
Malta fever, 321 
definition, 321 
etiology, 321 

pathological anatomy, 321 

physiology, 321 
synonyms, 321 
Malum coxae senile, 907 
Mammary glands, abnormal development 
in male, 874 

functional activity, 874 
adenocarcinoma of, 882 
adenoma of, 879 
atrophy of, 876 
carcinoma of, 880 

medullary, 881 

simple, 882 

squamous, 881 
chondroma of, 878 
congenital abnormalities, 874 
cystic adenoma of, 876 
cysts of, 882 
early development, 874 
fatty infiltration of, 877 
fibro-adenoma of, 877 
fibroma of, 877 
hemorrhages from, 875 
hyperemia of, 875 
hypertrophy of, 876 
inflammation of, 875 
intracanalicular fibroma of, 878 
lipoma of, 878 
lipomatosis of, 877 



1090 



INDEX 



Mammary glands, myomata of, 878 

myxoma of, 878 

osteoma of, 878 

pericanalicular fibroma of, 877 

myxomatous cancer of, 882 

results of cancer of, 882 

sarcoma of, 878 

scirrhous cancer of, 882 

supernumerary, 874 

syphilis of, 877 

tuberculosis of, 877 
Manostomulum lentis, 401 
Marantic thrombi, 73 
Marrow-lymph gland, 468 
Mast-cell granules, 434 
Mastigophora, 385 
Mastitis, acute, 875 
chronic, 876 

pathological anatomy, 875 
Maximow, polyblast of, 159 
Measles, 372 
Meat poisoning, 39 
Mechanical injury in etiology of disease, 

24 

Meckel's diverticulum, 656 
Medicinal leukocytosis, 444 
Mediterranean fever, 321 
Medullary canal, 932 

carcinoma, 240 

folds, 932 
Megacolon, 656 
Megakaryocytes, 433, 479 
Megaloblasts, 437, 480 
Megalocytes, 436 
Melanemia, 441 
Melanin, 109 
Melanoma, 207 
Melanosarcoma, 207 
Melanosis, 1023 
Melanuria, 801 
Melcena neonatorum, 642 
Membrane, tympanic, 1035 
Mendel's law, 23 
Meningismus, 953, 975 
Meningitis, cerebrospinal, 974 

epidemic cerebrospinal, 927 

changes associated with, 928 

influenzal, 313 

other organisms in, 292 

serous, 928 

tuberculous, 928, 975 

pathological anatomy, 928 
Meningocele, 923, 938 
Meningococcus, 291 
Menorrhagia, '68, 816 
Menstruation, 815 

abnormalities of, 816 
Mercury, action of, 36 
Merozoites, 391 
Mesarteritis, 525 

Mesenteric arteries, embolism of, 662 

thrombosis of, 662 
Mesothelioma of peritoneum, 732 
Metabolic pigmentation, 109 
Metabolism, carbohydrate, diseases of, 50 

disorders of, 41 

in diabetes, 54 

of fat, 42 

of phosphorus, 55 



! Metabolism, protein, disorders of, 46 
purin, disorders of, 48 
Metamorphoses, lipoid, 91 
! Metaplasia, 161 
I Metastases, pigment, 108 
Metastasis, 70 

of tumors, 174 
Metastatic calcification, 102 
Methemoglobin in urine, 806 ] 
Methemoglobinemia, 442 
Metrorrhagia, 68, 816 
Metritis, 817 
acute, 820 
chronic, 820 
! Metschnikoff's theory of immunity, 270 

Miasmatic diseases, 40 
'; Microblasts, 437 

Microcephaly, 939 
: Micrococcus catarrhalis, 298 
gonorrhoeae, 292 
lanceolatus, 294 
i melitensis, 321 
| tetragenus, 298 

Microgametocyte, 391 
! Micromyelia, 982 
! Microphthalmia, 1013 
Miescher's tubes, 396 
Mikulicz cells, 322 
Miliary aneurysm, 537 
of spinal cord, 986 
tubercle of human form, 150 
tubercles, 337 

of brain, 968 
tuberculosis, 339 
chronic, 602 
general, 600 
Milium, 1058 

Milk spots on pericardium, 522 
Miner's elbow, 911 
Mithridatization, 33 
Mitosis, 156 
Mixed infections, 267 
tumors, 248 

of testicles, 867 
Moist gangrene, 118 
Moles, fleshy, 856 
hydatid, 848, 858 
tubal, 848 
Molluscum bodies, 397, 1056 
contagiosum, 396, 1056 
appearances, 397 
definition, 396 
etiology, 397 
seats, 397 
structure, 397 
fibrosum, 179, 218 
Monckeberg's arteriosclerosis, 531, 534 
■ Mononuclear leukocytes, large, 431 
Monotrichous flagella, 257 
Monsters, 246, 251 
double, 246, 251 
single, 246, 251 
Morax-Axenfeld bacillus, 317 
Morbid anatomy, definition, 17 
! physiology, definition, 17 
Morbus cceruleus, 487 
Morgagnian cataract, 1022 
Mors thymica, 748 
Mosquitoes, role of, in malaria, 392 



INDEX 



1091 



Mosquitoes in yellow fever, 369 
Mouth, actinomycosis of, 627 

anemia of, 622 

atrophy of, 626 

circulatory disturbances, 622 

congenital abnormalities, 622 

degeneration of, 626 

hemorrhages of, 622 

hyperemia of, 622 

inflammation of, 622. See also Stoma- 
titis. 

lupus of, 627 

spirochetosis of, 624 

syphilis of, 627 

trench, 624 

tuberculosis of, 627 

tumors of, 628 
Movable spleen, 460 
Mucin, 94 

Mucoid degeneration, 94 
definition, 94 
etiology, 94 

microscopical appearances, 95 
of bone-marrow, 481 
pathological anatomy, 95 

physiology, 96 
seats, 96 
Mucopurulent cystitis, 793 

inflammation, 142 
Mucous patch of syphilis, 152, 354 
Multiple myeloma, 197 

sclerosis, 963, 964 
Mummification, 118 
Mumps, 373, 636 
Mural endocarditis, 489 
Muscle tissue, regeneration of, 160 
Muscles, actinomycosis of, 919 

anemia of, 912 

anthrax of, 919 

atrophy of, 915 

calcification of, 918 

coagulation-necrosis of, 918 

congenital malformations, 912 

diseases of, 912 

fatty degeneration of, 918 
infiltration of, 918 

glanders of, 919 

hemorrhages from, 912 

hyaline degeneration of, 918 

hyperemia of, 912 

hypertrophy of, 912 

inflammation of, 913 

parasites of, 919 

parenchymatous degeneration of, 
918 

rupture of, 913 

syphilis of, 919 

tuberculosis of, 918 

tumors of, 919 
Muscular atrophy, neuropathic, 915 

progressive spinal, 998 
Mutation, 24 
Myasthenia gravis, 916 
Mycetoma, 363 

black, 363 

etiology of, 363 

melanoid, 363 

pale, 363 

pathological anatomy, 363 



Mycobacterium influenza), 312 
leprae, 343 
mallei, 322 

tuberculosis, 332. See also Bacillus 
tuberculosis. 
Mycoses of skin, 1054 
Mycosis fungoides, 155, 208 
appearance, 208 
associated conditions, 209 
etiology, 208 
nature, 209 
structure, 208 
Mycotic endocarditis, 492 
Myelitis, 988 

hematogenous purulent, 988 
pressure, 989 

secondary to purulent leptomeningitis, 
988 

transverse, without local foci, second- 
ary to injury or infectious disease, 
988 

Myeloblasts, 479 
Myelocytes, 433, 479 
Myelocythemia, 443 
Myelogenous callus, 887 

leukemia, bone-marrow in, 482 

osteosarcoma, 206 
Myeloid leukemia, 455 

sarcoma, 206 
Myeloma, multiple, 197 

of bone-marrow, 483 

of bones, 902 
Myelomeningocele, 983 
Myeloplaxes, 132, 433, 479 
Myiasis, 421, 422 
Myocardite segmentate, 504 
Myocarditis, 506 

acute, 506 

circumscribed, 507 
diffuse, 508 

chronic, 509 

fibrous, 509 

parenchymatous, 500 
Myocardium, 500. See also Heart- 
muscle. 
Myofibroma of uterus, 824 

of vagina, 852 

of vulva, 854 
Myoglia, 176 
Myoma cavernosum, 220 

cysticum, 220 

lasvicellulare, 219 

of heart, 518 

of mammary glands, 878 

striocellulare, 222 
Myomalacia cordis, 489 
Myopathic muscular atrophy, 916 
Myositis, 913 

chronic, 914 
productive, 914 
suppurative, 914 

disseminated acute, 913 

hemorrhagic, 913 

localized acute, 913 

ossificans progressiva, 915 

ossifying, 914 

serous, 913 

suppurative, 913 
Myotonia congenita, 916 



1092 

Myxedema, 742 

Myxoid cystomata of ovaries, 836 
Myxoma, 180 

appearance of, 180 

definition of, 180 

etiology of, 180 

nature of, 181 

of bones, 901 

of heart, 518 

of mammary glands, 878 

seats of, 180 

structure of, 180 
Myxomatous cancer of mammary glands, 
882 

degeneration of testicles, 863 
Myxosarcoma, 180 

N^vus lymphaticus, 188 

prominens, 189 
Nagana, 387 
Nails, 1059 

inflammations of, 1059 

tumors of, 1059 
Narrowing of intestines, 657 
Nasal catarrh, acute, 550 

cavities, 549 

, anatomical considerations, 549 

circulatory disturbances, 549 

congenital abnormalities, 549 

edema, 549 

foreign bodies, 551 

hemorrhage, 549 

hyperemia, 549 

infectious diseases, 550 

inflammation, 550 

parasites, 551 

syphilis, 550 

tuberculosis, 550 

tumors, 551 
polyps, 178, 551 
Necator Americanus, 414 
Necrobiosis, 110, 113 
Necrosis, 110 
caseous, 148 

circulatory derangements in. Ill 
coagulation, 113. See also]Coagulation 

necrosis. 
definition of, 110 
etiology of, 110 
fat, 117 

fatty, of pancreas, 719 
focal, 118 

intoxications in, 111 

liquefaction, 115 
definition of, 115 
pathological anatomy, 115 

mechanical agents in, 112 

of bone-marrow, 481 

of bones, 894 

of liver, 694 

of lymphatic glands, 470 
of pancreas, 719 
of skin, 1043 

pressure, of pharynx, 634 
trophic derangements in, 111 

Necrotic inflammation, 142 

Negri bodies, 375 

Nematodes, 411 

Neoplasm, 164 



INDEX 

Nephritis, 756 

acute interstitial, sclerosis following, 
771 

arteriosclerotic, 774 
ascending suppurative, 770 
catarrhal, 762 
degenerative tubular, 762 
etiology, 756 

glomerular, sclerosis secondary to, 771 
interstitial nonsuppurative, acute, 769 

suppurative, acute, 769 
parenchymatous, 766 
pathology of, 761 
senile, 776 
Nephrolithiasis, 787 
Nephropathy, 762 
Nephrosis, 762 

Nerve, optic, atrophies of head, 1031 
sheaths, fibroma of, 178 
tissues, tumors from, 213 
Nerve-cells, 941 

functions of, 945 
Nerve-fibers, 946 
function of, 946 
Nerve-poisons, poisoning from, 34, 38 
Nerves, atrophy of, 1007 
degeneration of, 1007 
edema of, 1006 
hemorrhage of, 1006 
hyperemia of, 1006 
regeneration after injury, 1007 
Nervous shock, 25 

system, central, concussion of, 967 
injuries to, 967 
general pathologic anatomy of, 941 
inflammations of, 1008 
influence of, in inflammation, 125 
leprosy of, 1010 
peripheral, diseases of, 1006 
postmortem degenerative conditions 

of, 936 
sympathetic, 933 
syphilis of, 969, 1010 
tuberculosis of, 1010 
< tumors of, 1011 
tissue, regeneration of, 161 
I Neuritis, 1008 

interstitial, acute, 1008 
chronic, 1009 

hypertrophic, 1010 
parenchymatous, 1010 
suppurative, 1010 
Neuroblastoma, 216 
Neuroblasts, 932 
Neurocytoma, 215 
Neuro-epithelioma, 215 
Neurofibromatosis, 218 
Neuroglia, 176 

degeneration of, 948 
Neuroglioma, ganglionar, 970 
Neuroma, 215 
amyelinicum, 218 
false, 218, 219 
gangHocellulare, 218 
myelinicum, 218 
of nerves, 1011 
of suprarenal bodies, 747 
plexiform, 219 
Neuron, 935 



Neuroparalytic hyperemia, 63 
Neuropathic arthritis, 908 

hemorrhage, 67 

muscular atrophy, 915 
secondary, 916 
Neurotonic hyperemia, 63 
Neutrophiles, 432 
Neutrophilic granules, 434 
Nevus, 1041 
New growth, 164 

autonomous, 165 
Nigrities, 626 

Nipples, inflammation of, 875 
Nitrifying ferments, 261 
Nitrobacter, 261 

Nitrosomonas, Winogradsky's, 261 
Node, Keith-Flack, 505 

of Tawara, 505 
Nodes, Heberden's, 908 
Nodular leprosy, 345 
Noma, 625 

Non-contagious diseases, 39 
Normoblasts, 437 
Nosebleed, 68 
Notochord, 932 

Novy's theory of anaphylaxis, 285 
Nucleo-albuminuria, 802 
Nutmeg liver, 687 
Nutrition, disorders of, 41 
in disease, 20 

Obesitas cordis, 501 
Obesity, associated conditions, 43 
causes of ; 43 

pathological anatomy, 43 
Obligate aerobic bacteria, 258 

bacteria, 257 
Obliterating appendicitis, 669 
Obstruction of pancreatic duct, 724 
Obstructive biliary cirrhosis, 702 

thrombi, 76 
Occupation in disease, 20 
Ochronosis, 800 
Odontoma, 187 
(Edema ex vacuo, 79 
Oidiomycosis, 366 
Oidium albicans, 364 
Oligemia, 440 
Oligochromemia, 446 
Oligocythemia, 446 

Omental cavity, lesser, cystic accumula- 
tions in, 724 
Onychia, 1059 
Onychogryphosis, 1059 
Oochronosis, 110 
Oophoritis, 834 

Ophthalmitis, sympathetic, 1028 
Opisthorchis felineus, 399 
Opsonin theory of immunity, 271 
Opsonins, 127, 271 

Optic bulb, abnormalities in position of, 
1031 

nerve, atrophies of head, 1031 
hyperemia of, 1030 
inflammation of, 1030 
syphilis of, 1031 
tuberculosis of, 1031 
tumors of, 1031 
Orbit, 1031 



INDEX 1093 

Orbit, tumors of, 1031 
Orchitis, 863 
acute, 864 
chronic, 864 
etiology, 863 

pathological anatomy, 863 
Oriental sore, 388 
Orthostatic albuminuria, 802 
Ossification, 104 
Ossifying periostitis, 890 
Osteitis, fibrous, 893 
Osteo-arthropathy, hypertrophic, 890 
Osteochondroma, 184 
Osteoclasts, 892 
Osteogenesis imperfecta, 884 
Osteoid chondroma, 184 

sarcoma, 901 
Osteoma, 185 

appearance of, 186 
definition of, 185 
dental, 187 
durum, 186 
eburneum, 186 
etiology of, 185 
heteroplastic, 186 
nature of, 187 
of bones, 901 
of brain, 971 
of lungs, 606 
of mammary glands, 878 
of pleura, 620 
seats of, 187 
spongiosum, 186 
structure of, 187 
Osteomalacia, 896 
conditions associated with, 896 
definition, 896 
etiology, 896 

pathological anatomy, 896 
Osteomyelitis, 482 ? 891 

conditions associated with, 892 
cryptogenetic, 482 
definition, 891 
etiology, 891 

pathological anatomy, 891 
Osteophytes, 186 
Osteoporosis, inflammatory, 892 
Osteopsathyrosis, 895 
Osteosarcoma, 206 
myelogenous, 206 
true, 206 
Osteosclerosis, 893 
Osteotabes infantum,- 885 
Ostitis, 891 
chronic, 892 
etiology, 892 

pathological anatomy, 892 
condensing, 893 
conditions associated with, 892 
definition, 891 
deformans, 893 
etiology, 891 

pathological anatomy, 891 
Otitis, cystic, 1038 
media, 1036 
catarrhal, 1036 
purulent, 1037 
Ovarian pregnancy, 849 
Ovaries, anatomical considerations, 833 



1094 



INDEX 



Ovaries, carcinoma of, 839 

changes in position, 833 

colloid cystomata of, 836 

congenital abnormalities, 833 

congestion of, 834 

connective-tissue tumors of, 835 

cystic tumors of, 836 

dermoid cysts of, 839 

development of, 833 

follicular cysts of, 836 

glandular cystomata of, 836 

hemorrhage from, 834 

hyperemia of, 834 

inflammation of, 834 

papillary cystomata of, 837 

tuberculosis of, 835 

tumors of, 835 
Overaction of heart, 61 
Overfeeding, 42 
Oxalate of lime, in urine, 804 
Oxaluria, 54 

alimentary, 54 
Oxidizing ferments, 261 
Oxyphile granules, 433 
Oxyuris vermicularis, 412 
Ozena, 550 

Ozcena syphilitica seu tuberculosa, 550 

Pacchionian bodies, 930 
Pacemaker of heart, 505 
Pachydermia laryngis, 552 
Pachymeningitis, 921, 980 

cervicalis, 978 

external suppurative, 921 

hemorrhagic, internal, 978 

internal hemorrhagic, 921 

productive, 921 

tuberculous, external, 978 
Paget's disease of nipple, 1057 
Palate, cleft, 622 

Pancreas, amyloid infiltration of, 719 
atrophy of, 719 
carcinoma of, 723 

pathological physiology, 724 
cirrhosis of, 721 
congenital abnormalities, 718 
fatty necrosis of, 719 
hemorrhage of, 718 
hyperemia of, 718 
inflammation of, 720 
necrosis of, 719 
of cysts, 724 

parenchymatous degeneration of, 719 
pigmentation of, 719 
sarcoma of, 724 
syphilis of, 723 
tuberculosis of, 723 
tumors of, 723 
Pancreatic acne, 724 
apoplexy, 718 
calculi, 725 

disease, pathological physiology, 723 

duct, obstruction of, 724 
Pancreatitis, 720 

hemorrhagic, acute, 720 

indurative, chronic, 721 

suppurative, acute, 721 
Pandemic disease, 40 
Pangenesis, 22 



Pannus, 1016 

Papillary cystadenoma, 880 
cystomata of ovaries, 837 
Papuliferous cystoma, 245, 868 
Papillitis, 1030, 1031 
Papillo-edema, 1031 
Papilloma, 223 

appearance of, 224 
definition of, 223 
etiologv of, 223 
hard, 224 
nature of, 226 
of bladder, 797 
of larynx, 554 
of penis, 860 
of vagina, 852 
seats of, 224 
soft, 224 
structure of, 224 
i Papillomatous tumors of vulva, 854 
j Papules, 1045 
Paracolon infection, 308 
Paradoxical embolism, 70 
Paraglioma, 217 
Paragonimus kellicotti, 401 
; ringeri, 400 

westermanii, 401 
i Parakeratosis, 1047 
i Paralysis agitans, 963, 964 
ascending, Landry's, 992 
bulbar, 1000 
general progressive, 965 
glossiolabiolaryngeal, 1000 
j infantile, 378, 975, 990 
i Paramecium coli, 396 
Parametritis, 817 
Parametrium, 847 
Paraphimosis, 860 
Parapisthorcis caninus, 401 
Parasites, 257 
animal, 40 

diseases from, 382 
of intestines, 684 
in blood, 458 
of bones, 902 
of bronchi, 561 
of heart, 518 
of intestines, 684 
animal, 684 
vegetable, 684 
of kidney, 785 
of larynx, 555 
of liver, 710 
of lungs, 609 
of lymphatic vessels, 547 
of malaria, 389 
j of muscles, 919 

of nasal cavities, 551 
of pericardium, 523 
of peritoneum, 733 
of pleura, 621 
of spleen, 466 
of thyroid gland, 741 
of ureters, 791 
of uterus, 833 
vegetable, 39 
in blood, 458 
of intestines, 684 
Parasitic diseases, 40 



INDEX 



1095 



Parasitic stomatitis, 626 
theory of tumors, 168 
Parasyphilis, 356 
Parathyroid glands, 744 
Paratyphoid fever, 677 
infection, 308 
nature, 309 
Parenchymatous degeneration, 84 
of heart-muscle, 500 
of kidneys, 776 
of liver, 691 
of muscles, 917, 918 
of pancreas, 719 
giant-cells, 132 
glossitis, 626 
goiter, 736 
hemorrhage, 65 
hepatitis, 694 
inflammation, 134, 142 
myocarditis, 500 
nephritis, 766 
neuritis, 1010 
pneumonia, 573 
Paresis, 963, 965, 975 
Parinaud's conjunctivitis, 1016 
Paronychia, 1059 
Paroophoron, 833 
Parostitis, 890 

Parotid gland, tumors of, 637 
Parotitis, 636 

epidemic, 373 
Parovarium, 833 

cysts of, 840 
Paroxysm, gouty, 908 
Paroxysmal hemoglobinuria, 803 
Passive congestion of esophagus, 638 
Pathogenic bacteria, 257 
Pathological anatomy, definition, 17 

chemist^, definition, 17 

conditions of later life depending upon 
heredity, 22 

physiology, definition, 17 
Pathology, definition, 17 

general, 17 

special, 429 

definition of, 17 
Patulous ductus Botalli, 487 
Pearl disease, 151 
Pediculus capitis, 422 

corporis, 422 

pubis, 422 

vestamenti, 375 
Pellagra, 59 
Pemphigus, 1047 
Penis, carcinoma of, 861 

condyloma acuminatum, 860 

congenital abnormalities, 859 

epithelioma of, 861 

inflammation of, 860 

injuries of, 861 

papilloma of, 860 

syphilitic chancres on, 860 

tuberculosis of, 860 
Pentastoma taenioides, 421 
Pentosuria, 54, 800 
Peptic ulcer, 140, 646 
Perforation of esophagus, 640 
Peri-arteritis, 525 

nodosa, 528, 538 



I Peribronchial fibrous pneumonia, 588 
] Peribronchitis, 558 

Pericanalicular fibroma of mammary 
j glands, 877 
Pericarditis, 519 

acute, terminations of, 521 

associated conditions, 522 

dry, 520 

fibrinous, 520 

hemorrhagic, 521 

interna et externa, 522 

primary, 519 

purulent, 521 

secondary, 519 

serofibrinous, 520 
Pericardium, 519 

actinomycosis of, 523 

air in, 523 

dropsy of, 519 

hemorrhage of, 519 

hyperemia of, 519 

infectious diseases, 522 

inflammation of, 519. See also Peri- 
carditis. 

milk spots on, 522 

parasites of, 523 

syphilis of, 523 

tuberculosis of, 522 

tumors of, 523 
Perichondritis, 553, 1034 
Perihepatitis, 703 

hyperplastic, 730 
Perilymphadenitis, 471 
Perilymphangitis, 589 
Perimastitis, 876 j 
Perimetritis, 817 
Perinephritis, 756 
Periorchitis, 864 

prolifera, 865 
Periosteal callus, 887 
Periostitis, 889 

conditions associated with, 890 

definition, 889 

etiology, 889 

ossifying, 890 

pathological anatomy, 889 

purulent, 890 

results of, 890 

simple, 889 

syphilitic, 899 
Peripheral nervous system, diseases of, 

1006 
Periphlebitis, 543 
Periprostatitis, 869 
Perirenal hematoma, 755 
Perisplenitis, 467 

cartilaginea, 464 
Perithelioma, 209, 971 
Peritoneal cavity, echinococcus cysts of, 

733 

Peritoneum, carcinoma of, 732 
congenital abnormalities, 725 
dropsy of, 726 
endothelioma of, 732 
fibromata of, 732 
hemorrhage of, 725 
hyperemia of, 725 
inflammation of, 727 
lipomata of, 732 



1096 

Peritoneum, mesothelioma of, 732 
parasites of, 733 
sarcoma of, 732 
tuberculosis of, 730 
tumors of, 732 
Peritonitis, 727 
acute, effects of, 729 

general, 729 

localized, 728 
chronic, 729 
etiology, 727 

pathological anatomy, 728 
Peritrichous flagella, 257 
Perityphlitis, 666 ■ 
Periurethral abscesses, 808 
Perivascular fibrous pneumonia, 588 
Perles, epithelial, 237 
Pernicious anemia, progressive, 450 
blood in, 452 
definition of, 450 
etiology of, 450 
pathogenesis of, 450 
pathological anatomy, 451 
Pertussis, Bordet-Gengou bacillus of, 318 
Pes calcaneus, 903 
equinus, 903 
valgus, 903 
varus, 903 
Pest, 318 
Petechia, 68 
Petechia?, 66 

Petechial hemorrhages of pleura, 610 
Pfeiffer-Gruber-Durham phenomenon, 
m 278 

Pfeiffer's phenomenon, explanation of, 
279 

theory of immunity, 270 
Phagedenic ulceration of cervix, 820 

ulcers, 140 
Phagocytes, 127, 270 
Phagocytic cells, large mononuclear, in 

inflammation, 128 
Phagocytosis, 127, 131 

theory of immunity, 270 
Pharyngitis, catarrhal, 631 
chronic, 631 

phlegmonous, 631 

pseudomembranous, 632 
Pharyngomycosis leptothricia, 343, 635 
Pharynx, anemia of, 631 

congenital malformations of, 630 

diphtheria of, 634 

edema of, 631 

hemorrhages of, 631 

hyperemia of, 631 

pressure necrosis of, 634 

syphilis of, 635 

tuberculosis of, 635 

tumors of, 636 
Phimosis, 859, 860 
Phlebectasia, 73, 544 
Phlebitis, 542 

acute, 542 

chronic, 544 
Phleboliths, 77, 544 
Phlebosclerosis, 544 
Phlegmon, 139, 1053 
Phlegmonous cystitis, 794 

esophagitis, 638 



INDEX 

Phlegmonous inflammation, 139 
of vulva, 853 
pharyngitis, 631 
i prostatitis, 869 
stomatitis, 625 
; tonsillitis, 633 
Phloridzin glucosuria, 53 
Phlyctenular conjunctivitis, 1016 

keratitis, 1020 
Phosphates in urine, 805 
Phosphaturia, 55 
| Phosphorus, action of, 35 
metabolism of, 55 
Photogenesis of bacteria, 263 
Phthisis, acute caseous, 594 
bulbi, 1024 

chronic ulcerative, 594 
fibroid, 594, 599 
fibrous, 594 
Physiology, morbid, definition of, 17 

pathological, definition of, 17 
Physometra, 815 
Pia-arachnoid, 924, 979 
anemia of, 924 
calcareous infiltration of, 979 
cholesteatomata of, 931 
edema of, 924 
endothelioma of, 931 
hemorrhage of, 924, 979 
hyperemia of, 924, 979 
inflammation of, 925, 979 
lipoma of, 932 
sarcoma of, 931 
syphilis of, 930, 980 
teratoma of, 932 
tuberculosis of, 980 
j tumors of, 981 
! Pigment metastases, 108 
I Pigmentary cirrhosis, 702 
I degeneration of retina, 1028 
Pigmentation, 105 
coal-dust, 105 
from exterior, 105 
hematogenous, 106 

microscopic appearance, 108 
hepatogenous, 108 
metabolic, 109 
of bone-marrow, 481 
of erythrocytes, 437 
of liver, 690 

of lymphatic glands, 470 
of mucosa of intestines, 661 
of pancreas, 719 
of skin, 1041 

variations in, 1043 
of spleen, 465 
of stomach, 649 
of suprarenal bodies, 745 
Pineal gland, 751 
Pinguecula, 1017 
Pink-eye, 1016 
Pin-worm, 412 
Pirosoma bigeminum, 394 
Pituitary body, 748 
adenoma of, 750 
amyloid infiltration of, 750 
circulatory disturbances of, 749 
colloid degeneration of, 750 
cysts of, 750 



Pituitary body, hypertrophy of, 749 

infectious diseases of, 750 

inflammation of, 749 

pathological physiology, 750 

sarcoma of, 750 

tumors of, 750 
Pityriasis versicolor, 1055 
Placenta, abnormalities of development, 

855 

calcification of, 856 
degenerations of, 856 
edema of, 856 
inflammations of, 857 
prsevia, 855 
succenturiata, 855 
syphilis of, 857 
tuberculosis of, 857 
Placental apoplexy, 856 
infarcts, 856 
polypi, 856, 858 

site, destructive epithelial tumor of, 
250 

Placentitis, 857 

Plague, bubonic, 318. See also Bubonic 
plague. 

Plants, toxalbumins from, poisoning 

from, 36 
Plaques jaunes, 959 
Plasma cells, 433, 468 

in inflammation, 129 

of Waldeyer, 129 

of blood, 429, 435 
hyperinosis of, 439 
hypinosis of, 439 
pathological changes in, 439 
Plasmodia, parthenogenesis of, 392 

sporogony of, 391 
Plasmodium falciparum, 389, 391 

malarise, 389, 391 

vivax, 389, 390 
Plethora, 439 

apocoptica, 440 

hydremica, 440 

vera, 439 
Pleura, 609 

active hyperemia, 610 

anatomical considerations, 609 

carcinoma of, 621 

chondroma of, 620 

chylous effusion in, 611 

circulatory disturbances, 610 

dropsy of, 611 

endothelioma of, 620 

fibroma of, 619 

infectious diseases, 618 

inflammation of, 612. See also Ple- 
uritis. 

lipoma of, 619 

osteoma of, 620 

parasites of, 621 

passive hyperemia, 610 

petechial hemorrhages, 610 

sarcoma of, 620, 621 

syphilis of, 619 

tuberculosis of, 618 

tumors of, 619 
Pleural thickening, chronic, 616 
Pleurisy, 612. See also Pleuritis. 
Pleuritis, 612 



INDEX 1097 

Pleuritis, associated lesions, 618 
bread-and-butter, 614 
chronic, 616 
.etiology of, 612 
fibrinous, 614 
hemorrhagic, 616 
pathological anatomy, 614 

physiology, 618 
purulent, 615 
serofibrinous, 614 
tuberculous, 618 
Pleurogenic fibrous pneumonia, 587 

purulent pneumonia, 589 
Plexiform angiosarcoma, 209 

neuroma, 219 
Pneumaturia, 801 

Pneumobacillus of Friedlander, 297 
Pneumococcus, 294 
Pneumonia, 294, 572 
alba, 603 

aspiration, 578, 581 
bronchogenic purulent, 588 
catarrhal, 572, 578 

cheesy, 572, 582. See also Pneumonia, 

tuberculous. 
classification of, 572 
congenital syphilitic, 588 
croupous, 294, 573. See also Croupous 

pneumonia. 
deglutition, 578 
desiccans, 589 

fibrinous, 294, 572, 573. See also 
Croupous pneumonia. 
associated lesions, 576 
definition of, 573 
etiology of, 573 
pathological anatomy, 574 

physiology, 576 
stage of congestion or engorgement, 
574 

of consolidation or hepatization, 
574 

terminations, 577 
fibrous, 572, 577, 584 
classification of, 584 
definition of, 584 

of resolution, 576 
unusual characters, 576 
pathological anatomy, 586 
peribronchial, 588 
perivascular, 588 
pleurogenic, 587 
secondary, 587 
hematogenic purulent, 588 
hypostatic, 578, 581 
interstitial, 573 

lobar, 294, 573. See also Croupous 

pneumonia. 
lobular, 578 
migrans, 574 
other forms of, 297 
organisms in, 298 
parenchymatous, 573 
pleurogenic purulent, 589 
productive, 572, 584 
purulent, 588 

associated lesions, 590 
bronchogenic, 588 
definition of, 588 



1098 



INDEX 



Pneumonia, purulent, hematogenic, 588 

pleurogenic, 589 

terminations of, 589 
syphilitic, congenital, 588 
tuberculous, 582 

associated lesions, 584 

definition of, 582 

etiology of, 582 

pathological anatomy, 583 
Pneumonic tuberculosis, 593 

acute, 594 

chronic, 595 
Pneumonitis, 572 
universalis, 583 
Pneumonokoniosis, 105, 585 
Pneumonomycosis aspergillina, 343, 609 
Pneumopericardium, 523 
Pneumopyopericardium, 523 
Pneumothorax, 611 

closed, 612 
Poikilocytosis, 436 

Poisons, blood-poisoning from, 34, 37 

classification of, 33 

corrosive, action of, 33, 34 

defense of body against, 32 

effect of, 33 

elimination of, 33 

fate of, after ingestion, 32 

general action, 32 

in disease, 21 

in etiology of disease, 32 

nerve-, poisoning from, 34, 38 

organic, action of, 33, 34 

parenchyma, action of, 33, 34 
Polar granules, 256 
Polio-encephalitis, 992 
Poliomyelitis, 378, 975 

acute anterior, 990 

chronic anterior, 998 

etiology of, 378 

immunity to, 379 

superior, 992 

transmission of, 379 
Polyblast, 128 

of Maximo w, 159 
Polycholia, 442, 717 
Polychromatophilia, 437 
Polycoria, 1022 
Polycythemia, 442 

with chronic cyanosis and enlarged 
spleen, 443 
Polymastia, 874 

Polymorphonuclear leukocytes, 432 

leukocytosis, 443 
Polymyositis, 913 

secondary acute, 918 
Polyneuritis, 1010 
Polynuclear leukocytes, 432 
Polyorchism, 862 
Polypi, nasal, 178, 551 

of larynx, 555 

of uterus, 824 

placental, 856, 858 
Polypoid outgrowths of bladder, 797 

tumors of urethra, 810 
Polyuria, 799 
Porencephaly, 940 

etiology, 940 

pathological anatomy, 940 



Porencephaly,traumatic, 968 
Pork tapeworm, 403 
Porocephalus constrictus, 421 
Portal cirrhosis, 697 

vein, embolism of, 688 
thrombosis of, 688 
Port-wine stains, 189 
Posterior sclerosis, 993 

urethritis, 808 
Posthitis, 860 

Postmortem alterations, 119 

degenerative conditions in nervous 
system, 936 

lividity, 61 
Pott's disease, 899 
Precipitin, 278 
Pregnancy, abdominal, 849 

corpus luteum of, 834 

extra-uterine, 847 

interstitial, 848 

kidney of, 762 

ovarian, 849 

tubal, 848 
Preparateur, 268 
Pressure necrosis of pharynx, 634 

pathological effects, 24 
Pressure-atrophy, 84 
Pressure-myelitis, 989 
Primary simple arteriolar sclerosis, 772 
; Prior and Finkler, spirillum of, 350 
Procidentia, 813 
Proctitis, 669 

Productive endarteritis, 527 

inflammation, 134, 142 

pachymeningitis, 921 

pneumonia, 572, 584 
Progressive muscular atrophy, 915 

paralysis, general, 965 

spinal muscular atrophy, 998 

tissue changes, 163 
Prolapse of rectum, 661 

of uterus, 813 

of vaginal walls, 849 
Proliferation cysts, 244 
Proliferative changes in inflammation, 
131 

cystoma, 245 
Proptosis, 1031 
Prostate, abscess of, 869 

amylaceous bodies of, 870 

atrophy of, 869 

carcinoma of, 873 

concretions of, 870 

cysts of, 873 

fatty degeneration of, 870 

hypertrophy of, 870 
results, 873 

inflammation of, 869 

sarcoma of, 873 

tuberculosis of, 870 

tumors of, 872 
Prostatitis, 869 

chronic, 869 

phlegmonous, 869 

simple, 869 

suppurative, 869 
Protein, bacterial, 259, 287 

metabolism, disorders of, 46 
Proteolytic ferments, 260 



INDEX 



1099 



Proteus bacillus, 368 

infection, 368 
Prothrombin, 74 
Protozoa, 382 
Proud flesh, 140 
Prowaczek's chlamydozoa, 380 
Prurigo, 1050 
Psammoma, 103, 212 

bodies, 102 

of brain, 971 
Pseudarthroses, 888 
Pseudobacilli, 436 
Pseudodiphtheria bacilli, 303 
Pseudohermaphroditism, 859 
Pseudohydrophobia, 377 
Pseudohypertrophic muscular atrophy, 

916 

Pseudoleukemia, 192, 457 

cutis, 209 

infantum, 445, 457 
Pseudomelanosis, 110 
Pseudomembranous conjunctivitis, 1014 

cystitis, 794 

enteritis, 664 

esophagitis, 638 

gastritis, 643 

inflammation, 135, 136 

pharyngitis, 632 

stomatitis, 625 

vaginitis, 850 
Pseudomucin, 95 
Pseudomyxoma peritonei, 732 
Pseudoplasm, 164 
Pseudotrichinosis, 914 
Pseudotuberculosis, 342 
Psoriasis, 1050 
Psorospermiae, 394 
Pterygium, 1017 
Ptomains, poisoning from, 38 
Ptosis, congenital, 1013 

of eyelids, 1032 
Ptyalism, 626 

Puerperal atrophy of uterus, 823 
infections, 820 
etiology, 820 

pathological anatomy, 820 
Pulmonary artery, stenosis and atresia of, 
486 

infarcts, 73 
Pulp of teeth, inflammation of, 630 
Punctate wounds of brain, 967 
Purin metabolism, disorders of, 48 
Purkinje cells, 484 
Purpuras, 367 
Purulent arthritis, 904 

infiltration, 139 

inflammation, 142 

iritis, 1023 

lymphangitis, 589 

pericarditis, 521 

periostitis, 890 

pleuritis, 615 

pneumonia, 588 

vaginitis testis, 865 
Pustules, 140, 1046 

malignant, 326, 1052 
Putrefaction, 260 
Putrefactive changes, 120 
Pyelitis, 756 



Pyelonephritis, 769, 770, 789 
Pyemia, 266 

Pyknomorphous state, 943 
Pyknosis, 112 
Pylephlebitis, 689 
Pyocyanase, 272 
Pyogenic albumosuria, 802 

membrane, 139 
Pyometra, 815 
Pyonephrosis, 770, 787, 789 
Pyopagus, 251 
Pyopericardium, 521 
Pyopneumothorax, 612 
Pyorrhea alveolaris, 624 
Pyosalpinx, acute, 843 

chronic, 845 
Pyothorax, 615 

Pyramidal tract, degeneration of, 956 
tracts, 981 

Quincke's edema, 1045 
Quinsy, 633 

Rabies, 375 
etiology of, 375 
from bites, 376 

microscopical appearance, 377 

pathology of, 377 

period of incubation in, 376 

preventive inoculation for, 376 

season for, 376 

virus of, 375 
Race in disease, 20 
Racemose cysticerci, 404 
Rachischisis, 884, 983 
Rachitic rosary, 885 
Rachitis, 885. See also Rickets. 
Radium rays in etiology of disease, 31 
Rainey's tubes, 396 
Ranulse, 243 
Rat bite fever, 359 
Ray fungus, 360 
Reaction of Gruber-Widal, 272 
Receptors, 276 

of first order, 277 

of second order, 277 

of third order, 279 
Recklinghausen's disease, 218 
Rectum, inflammation of, 669. See also 
Proctitis. 

prolapse of, 661 
Recurrent fibroid tumor, 201 
Recurring appendicitis, 668 
Red corpuscles, 413. See also Erythro- 
cytes. 

softening of brain, 958 
Regeneration, 155 

after injury of a nerve, 1007 
definition of, 155 
etiology of, 155 

new formation of blood-vessels in, 159 

of adipose tissue, 160 

of bone, 159, 887 

of cartilage, 159 

of epithelium, 157 

of fibrous connective tissue, 158 

of glandular organs, 160 

of muscle tissue, 160 

of nervous tissue, 161 



1100 

Regeneration, pathological anatomy, 156 

physiology, 157 
Relapsing appendicitis, 668 
fever, 357 

definition, 357 

etiology, 357 

pathological anatomy, 357 
physiology, 358 
Renal arteries, embolism of, 755 

diabetes, 53 

glucosuria, 53 

hematuria, 803 

pelvis. See Kidney pelvis. 

sand, 788 

sclerosis, 771 

veins, thrombosis of, 755 
Repair, inflammation and, interpreta- 
tion of, 133 

of wounds, 143 
Reproductive organs, diseases of, 811 
Resolution after inflammation, 146 
Respiratory air, insufficiency of, in 
etiology of disease, 30 

system diseases, 549 
Rests, 745 

embryonic, 166 
Retention cysts, 243 
Retina, 1013, 1026 

anemia of, 1026 

atrophy of, 1027 

detachment of, 1027 

glioma of, 215 

hemorrhage of, 1027 

hyperemia of, 1026 

inflammation of, 1027 

pigmentary degeneration of, 1028 

syphilis of, 1028 

tuberculosis of, 1028 

tumors of, 1028 
Retinitis, 1027 

albuminuric, 1027 

chronic, 1028 

diabetic, 1027 

pigmentosa, 1028 

purulent, 1027 
Retroflexion of uterus, 812 
Retrograde change, 162 

embolism, 69 
Retrogressive processes, 82 
Retroperitoneal hernia, 658 
Retropharyngeal abscess, 632 
Retro-uterine hematocele, 817 
Retroversion of uterus, 813 
Rhabdomyoma, 222 

appearance of, 222 

definition of, 222 

etiology of, 222 

nature of, 222 

of heart, 518 

seats of, 222 

structure of, 222 
Rhabdomyosarcoma, 783 
Rhachischisis, 938 
Rheumatic endocarditis, 491 
Rheumatism, 377 

acute, 904 

conditions associated with, 905 
results, 904 

definition of, 377 



INDEX 

Rheumatism, etiology of, 377 
Rheumatoid arthritis, 905 
Rhinitis, acute, 550 
atrophica, 550 
chronic, 550 
diphtheritic, 550 
hypertrophic, 550 
Rhinoliths, 551 
Rhinoscleroma, 155, 321, 551 
Rhizopoda, 382 

Ribbert's theory of tumors, 167 
Rice-water discharges, 672 
Ricin, poisoning from, 36 
Rickets, conditions associated with, 886 
definition of, 885 
etiology, 885 

pathological anatomy, 885 
Rigor mortis, 120 
1 Ring bodies, 437 

of malaria, 391 
Ringworm, 367, 1054 
! Rocky Mountain fever, 380 
Rontgen rays. See X-rays. 
Round ulcer, 646 

of stomach, 140 
Round-cell infiltration in inflammation, 
131 

sarcoma, 203 
Round-worms, 411, 417 
Rubeola, 372 
Rupia, 152 

Rupture of bladder, 792 
of choroid, 1025 
of esophagus, 640 
of heart, 518 
of intestines, 685 
of fiver, 704 
of muscles, 913 
of spleen, 461 

of tympanic membrane, 1035 
of uterus, 815 
Russell's fuchsin bodies, 93, 113 

i Saccharomyces busse, 365 
hominis, 365 
tumefaciens, 365 
i Saccharomycosis, 155, 365 
! Saccular aneurysm, 538, 540 
bronchiectasis, 560 
Sago spleen, 465 
j Salivary ducts, diseases of, 637 

glands, inflammation of, 636. See also 
Parotitis. 
j Salpingitis, acute, 842 
chronic, 844 
diphtheritic, 844 
nodosa, 845 

pathological anatomy, 843 
Sand, bone, 898 

renal, 788 
Sapremia, 266, 822 
Saprophytes, 257 

Sarcinse ventriculi in gastric contents, 651 
Sarcoma, 198 

alveolar, 199, 204 
appearances of, 198 
deciduocellulare, 250 
definition of, 198 
etiology of, 198 



Sarcoma, giant-cell, 205 

intracanalicular, 879 

localized, 879 

myeloid, 206 

nature of, 201 

of bones, 901 

of brain, 970 

of Fallopian tubes, 849 

of heart, 518 

of intestines, 680 

of kidney, 782 

of liver, 707 

of lungs, 606 

of lymphatic glands, 479 

of mammary glands, 878 

of nerves, 1011 

of pancreas, 724 

of peritoneum, 732 

of pia-arachnoid, 931 

of pituitary body, 750 

of pleura, 620, 621 

of prostate, 873 

of skin, 1056 

of spinal cord, 1005 

of spleen, 466 

of suprarenal bodies, 747 

of testicles, 867 

of trachea, 556 

of urethra, 810 

of uterus, 827 

of vagina, 852 

of vulva, 854 

osteoid, 901 

round-cell, 203 

seats of, 199 

secondary, 199 

spindle-cell, 201 

structure of, 199 
Sarcomatosis, 199 
Sarcomatous cylindroma, 210 
Sarcoptes scabiei, 422 
Sarcosporidia, 396 
Scabies, 1055 
Scales, 1046 
Scar, 144 
Scarlatina, 372 
Scarlet fever, 372 
Schaudinn's bacillus, 351 
Schick test in diphtheria, 300 
Schistocyte, 436 
Schistosomum cattoi, 400 

haematobium, 399 

japonicum, 400 

mansoni, 400 
Schizomycetes, 253, 254 
Scirrhous carcinoma, 240 

of mammary glands, 882 
Sclera, 1012, 1021 

inflammation of, 1021 

injury to, 1021 
Sclerema, 1043 
Scleritis, 1021 
Scleroderma, 1042 
Sclerosis, amyotrophic lateral, 997 

arteriolar benign, 772 
primary simple, 772 

combined, 1000 

congenital, 938 

following acute interstitial nephritis, 1 



INDEX 1101 

Sclerosis, lateral, 1000 
lobar, 963 
multiple, 963 
of brain, atrophic, 948 

diffuse, 948 

disseminated, 948, 964 

hypertrophic nodular, 949 

multiple, 964 
posterior, 993 

etiology, 993 

pathological anatomy, 994 
renal, 771 

secondary to glomerular or diffuse 
nephritis, 771 
Scrofula, 340, 474 
Scrofulous catarrh, 550 

lymphadenitis, 474 
Scrotum, cysts of, 861 
elephantiasis of, 861 
epithelioma of, 861 
Scurvy, 368 
Scutula, 1054 
Seat-worm, 412 
Sebaceous cysts, 1058 
glands, 1057 

inflammation of, 1050 
tumors of, 1058 
j Seborrhea, 1057 
j Seborrhcea oleosa, 1057 

siccum, 1057 
j Secondary acute polymyositis, 918 
Segmentation of fibers of heart-muscle. 
504 

Sella turcica, 748 

Seminal vesicles, carcinoma of, 874 
concretions of, 874 
inflammation of, 874 
tuberculosis of, 874 
Senile arthritis of hip, 907 
atrophy of brain, 964 

of uterus, 923 
dementia, 963 
emphysema, 570 
nephritis, 776 
vaginitis, 851 
Senility, 82 

Sensitizing dose of serum, 283 
Septic endocarditis, 492 
Septicemia, 266 

sputum, 295 

typhoid, 303 
Serofibrinous inflammation, 135 

pericarditis, 520 

pleuritis, 614 

vaginitis testis, 865 
Serpent venom, poisoning from, 37 
Serpiginous ulcers, 140 
j Serous arthritis, 904 

inflammation, 134 

meningitis, 928 
■ Serum, antistreptococcus, 291 

blood-, hyper tonicity of, 439 

intoxicating dose, 283 

lytic action, 271 

sensitizing dose, 283 

sickness, 283 
Sex in disease, 20 
Shadow corpuscles, 437 
71 I Shell shock, 26 



1102 



INDEX 



Shell shock, hemorrhage in, 954 
Shock, anaphylactic, 282 

anesthetic, 25 

causes of, 25 

from hemorrhage, 25 

from traumatism, 25 

nervous, 25 

shell, 26 

hemorrhage in, 954 

surgical, 25 
Sialorrhea, 626 
Sickness, serum, 283 

sleeping, 371 
Side-chain theory, Ehrlich's, of im- 
munity, 275 
Siderosis,. 105, 585. 
Silicosis, 585 

Simple muscular atrophy, 916 
Sinus arrhythmia, 505 
catarrh, 471 

thromboeKf of dura mater, 920 
Sinuses, 139 
Skin, 1040 

actinomycosis of, 1054 

anatomy of, 1040 

anemia of, 1044 

angioma of, 1056 

atrophy of, 1041 

basocellular epithelioma of, 1057 

benign cystic epithelioma of, 1057 

circulatory disturbances of, 1044 

congenital abnormalities of, 1041 

crusts of, 1046 

edema of, 1045 

epithelial tumors of, 1056 

epithelioma of, 1056 

fibroma of, 1056 

glanders of, 1054 

hemorrhage into, 1044 

hyperemia of, 1044 

hypertrophy of, 1041 

inflammation of, 1045 

lenticular carcinoma of, 1057 

lipoma of, 1056 

mycoses of, 1054 

necrosis of, 1043 

pigment of, 1041 

regeneration of, 1043 

sarcoma of, 1056 

scales of, 1046 

specific inflammations of, 1053 
squamous epithelioma of, 1057 
syphilis of, 1053 
tubercles of, 1045 
tuberculosis of, 1053 
tumors of, 1056 
ulcers of, 1053 

variations in pigmentations of, 1043 
Skull, absence of, 937 

imperfect closure of, 938 
Sleeping sickness, 371 
Small-pox, 373 
Smegma bacillus, 342 
Snake-venom, poisoning from, 37 
Soft cancer of mammary gland, 881 

chancre, 320. See also Chancre, soft. 
Softening cysts, 243 
Soil transmission of disease, 425 
Solitary tubercles of brain, 968 



Sore, oriental, 388 
Specific inflammations, 147 
Spermatic artery, embolism of, 863 
Spermatocele, 868 
Sphacelus, 119 
Spina bifida, 983 

Spinal cord, abnormal smallness of, 982 
absence of, 982 
anatomy of, 981 
anemia of, 986 
carcinoma of, 1005 
circulatory disturbances of, 985 
congenital abnormalities of, 982 
cysts of, 1005 

degenerations in white matter of, 
1000 
primary, 992 
secondary, 1003 
dilatation of central canal of, 983 
diseases of, 978 
double, 983 
hemorrhages of, 986 
heterotopia of, 983 
hyaline degeneration of, 986 
hyperemia of, 986 
inflammation of, 988 
primary degenerations of, 992 
sarcoma of, 1005 
syphilis of, 992 
tuberculosis of, 992 
tumors of, 1005 
varicose veins of, 986 
ganglia, diseases of, 1006 
muscular atrophy, progressive, 998 
nerves, diseases of ganglia of, 1006 
Spindle-cell sarcoma, 201 
Spirilla, diseases due to, 347 
Spirillaceae, 254 
Spirillum, 255 
berolinense, 351 
cholerse asiaticse, 347 
duttoni, 357 
metschnikovii, 350 
of Finkler and Prior, 350 
tyrogenicum, 350 
vincenti, 358 
Spirochseta carteri, 357 
duttoni, 357 
icterohemorrhagica, 359 
morsus muris, 359 
muris ratti, 359 
nodosa, 359 
novyi, 357 
obermeieri, 357 
pallida, 351, 352 
! pertenue, 358 
Spirochetal gingivitis, 624 
Spirochetes, diseases due to, 351 
j Spirochetosis of mouth, 624 
| Splanchnoptosis, 650, 753 
Spleen, abnormal development and situa- 
tion, 460 
abscess of, 463 
absence of, 460 
amyloid infiltration, 465 
anatomical considerations, 459 
angioma of, 466 
atrophy of, 464 
bacony, 465 



INDEX 



1103 



Spleen, calcification of, 465 

carcinoma of, 466 

chronic hyperplasia of, 463 

circulatory disturbances of, 460 

cyanotic induration, 461 

cysts of, 466 

degeneration of, 464 

effect of removal, 460 

embolism of artery of, 461 

endothelioma of, 466 

fibroma of, 466 

function of, 459 

hemorrhage in, 461 

hyaline degeneration, 465 

hyperemia of, 460 

in leukemia, 465 

in Hodgkin's disease, 465 

infectious diseases of, 466 

inflammation of, 461 

lymphangioma of, 466 

movable, 460 

parasites of, 466 

pathological physiology, 459 

pigmentation of, 465 

rupture of, 461 

sago, 465 

sarcoma of, 466 

syphilis of, 467 

thrombosis of vein of, 461 

tuberculosis of, 466 

tumors of, 466 
Splenic anemia, 449, 460, 464 

fever, 326 

stones, 461 
Splenitis, 461 

chronic, 463 

circumscribed, 463 

diffuse, 462 

terminations of, 462 

spodogenous, 465 
Splenization of lungs, 572 
Splenolymph gland, 468 
Splenomegaly, 449, 464 

Gaucher's, 464 

idiopathic, 464 

primary, 464 
Spodogenous splenitis, 465 
Spondylitis deformans, 908 
Spongioblasts, 932 
Spore, 255 

Sporothricosis, 155, 366 
Sporothrix schencki, 366 
Sporozoa in birdsj and cold-blooded 

animals, 394 
Spotted fever, 292 
Spring catarrh, 1014 
Sprue, 365 

Spurious aneurysm, 536, 542 
Sputum septicemia, 295 
Squamous epithelioma, 236 
Stains, port-wine, 189 
Staphylococcus epidermidis albus 
Welch, 288 
group, 286 

pyogenes albus, 286, 288 
aureus, distribution, 287 
pathogenicity of, 287 
pathological physiology, 287 
citreus, 288 



Staphyloma, 1019 
Starvation, 41 
Stasis, 64, 122 

Status lymphaticus, 468, 748 
primary, 469 
secondary, 469 
thymicus, 469 
Steapsin, 117 
Stegomyia calopus, 369 

fasciata, 369 
Stenosis of bile-ducts, 713 
of bronchi, 559 
of esophagus, 639 
of Fallopian tubes, 841 
of intestines, 657 
of larynx, 554 
of uterus, 815 
of vagina, 849 
Stercoral typhlitis, 666 
Stimulation cells, 433 
Stokes-Adams' syndrome, 506 
Stomach, alterations in position of, 650 
amyloid infiltration of, 649 
anemia of, 641 
atrophy of glands of, 648 
calcification of, 649 
carcinoma of, 651 
congenital defects of, 641 
connective-tissue tumors of, 651 
degenerations of mucous membranes 

of, 649 
dilatation of, 650 
epithelial tumors of, 651 
fatty degeneration of, 649 
hemorrhage from, 68, 641 
hyperemia of, 641 
infectious diseases of, 651 
inflammation of mucosa of, 642 
leather-bottle, 645 
pigmentation of, 649 
round ulcer, 140 
softening of walls of, 650 
tumors of, 651 
Stomatitis, 622 
aphthous, 623 

associated conditions in, 626 
catarrhal, 622 
croupous, 623 
gangrenous, 625 
leukemic, 628 
j parasitic, 626 

phlegmonous, 625 
pseudomembranous, 625 
ulcerative, 624 
Stomoxys calcitrans, 379 
Stones, fecal, 105 
Strangulated hernia, 659 
Strangulation of hernia, internal, 659 
Stratified thrombi, 75 
Strawberry tongue, 623 
j Streptococcus, distribution of, 289, 291 
of j epidemicus, 289 
erysipelatis, 288 
hemolyticus, 289 
intracellularis meningitidis, 291 
mitior, 289 
mucosus, 289 
pathogenesis of, 290, 292 
pathological physiology, 290, 292 



1104 

Streptococcus pneumoniae, 288 
seu lanceolatus, 294 

pyogenes, 288, 373 
seu erysipelatis, 288 

rheumaticus, 289, 378 

viridans, 289 
Streptothrix madurse, 363 
Stricture of urethra, 809 
Strongyloides intestinalis, 416 

stercorals, 416 
Strongyloplasmia hominis, 397 
Strongylus apri, 421 

subtilis, 421 
Struma, 736. See also Goiter. 
Strumitis, 740 . . 
Stye, 1032 

Subcutis, inflammations of, 1052 

Subinfection, 267 

Substance sensibilisatrice, 268 

Substernal goiter, 736 

Sudamina, 1058 

Suffocation, 30 

Suffocative catarrh, 559 

Suffusion, 68 

Suggillation, 68 

Sulphates in urine, 806 

Sulphur granules, 361 

Superior poliomyelitis, 992 

Supernumerary mammary glands, 874 

Suppurative cholangitis, 712 

diseases, 286 
definition, 286 
etiology, 286 

encephalitis, 961 

enteritis, 664 

external pachymeningitis, 921 
inflammation, 137, 142 
keratitis, 1020 
lymphadenitis, 471 
myositis, 913 
neuritis, 1010 
pancreatitis acute, 721 
prostatitis, 869 
thyroiditis, acute, 736 
Suprarenal bodies, 744 

accessory, 745 

adenoma of, 747 

anatomical conditions, 744 

congenital anomalies, 745 

fatty degeneration of, 745 

gliomata of, 747 

hemorrhage of, 746 

hypernephroma of, 747 

inflammation of, 747 

neuroma of, 747 

physiological functions, 744 

pigmentation of, 745 

sarcoma of, 747 

syphilis of, 746 

tuberculosis of, 745 

tumors of, 747 
Surgical kidney, 769 

shock, 25 
Surra, 387 
Sweat, colored, 1058 
malordorus, 1058 
Sweat-glands, 1058 

inflammation of, 1058 
Swelling, cloudy, 84, 101 



INDEX 

Swelling, cloudy, definition of, 84 
etiology of, 84 
of heart, 500 
pathological anatomy, 85 

physiology, 86 
seats of, 86 
white, 910 
Sycosis, 1050 
Symblepharon, 1017 
Sympathetic ophthalmitis, 1028 
Sympathoblastoma, 216 
Symptomatic anemia, 446 
Syncephalus, 252 
Syncytial cells, 251 
Syncytioma malignum, 250, 859 

of Fallopian tubes, 847 
Syncytium, 855 
\ Syndrome, Stokes-Adams', 506 
' Synechia, 1024 
annular, 1023 
total posterior, 1023 
Synophthalmia, 1013 
Synovitis pannosa, 905 
Syphilis, 152, 351 
chancre of, 152 
condyloma latum of, 152 
congenital, 356 
constitutional, 354 
definition of, 351 
etiology of, 351 
gumma of, 152, 354, 355 
histology of, 152 
mucous patch of, 152, 354 
of arteries, 535 
of bladder, 795 
of blood-vessels of brain, 969 
of bones, 899 
of brain, 968 
of bronchi, 561 
of cervix uteri, 823 
of choroid, 1026 
of ciliary body, 1025 
of conjunctiva, 1017 
of cornea. 1020 
of dura mater, 922, 979 
of esophagus, 640 
of external ear, 1035 
of Fallopian tubes, 846 
of heart, 518 
of intestines, 679 
of iris, 1024 
of joints, 911 
of kidney, 780 
of larynx, 554 
of liver, 704 
of lungs, 603 
of lymphatic glands, 476 

vessels, 547 
of mammary glands, 877 
of middle ear, 1038 
of mouth, 627 
of muscles, 919 
of nasal cavities, 550 
of nervous system, 969, 1010 
of optic nerve, 1031 
of pancreas, 723 
of pericardium, 523 
of pharynx, 635 
of pia-arachnoid, 930, 980 



Syphilis of placenta, 857 
of pleura, 619 
of retina, 1028 
of skin, 1053 
of spinal cord, 992 
of spleen, 467 
of suprarenal bodies, 746 
of testicles, 867 
of thymus gland, 748 
of thyroid gland, 741 
of tympanic membrane, 1035 
of trachea, 556 
of urethra, 810 
of vagina, 852 
of veins, 545 
of vulva, 853 

pathological anatomy, 353 

physiology, 356 
secondary lesions, 152, 354 
tertiary lesions, 152, 354 
Syphilitic bubo, 354 
cirrhosis, 703 

fibrous induration of lung, 605 

fungus of testicles, 867 

gumma of lungs, 604 

periostitis, 899 

pneumonia, congenital, 588 
Syphiloma, 354 
Syringomyelia, 984 

false, 987 

Tabardillo, 375 
Tabes dorsalis, 975, 993 

mesenterica, 476 
Tachycardia, auricular, 506 
Taenia echinococcus, 402, 406 

elliptica, 406 

flavopunctata, 406 

solium, 403 

saginata, 404 

adult, in man, 404 
geographical distribution, 404 
larval state, in man, 403 
Tapeworms, 401 

beef,. 404 

dwarf, 405 

pathological physiology, 402 

pork, 403 
Taraxigen, 285 
Taraxin, 285 
Taraxy, 285 
Tawara, node of, 505 
Teeth, anomalous development of, 629 

caries of, 629 

Hutchinson's, 356, 629 

inflammation of pulp of, 630 
Telangiectatic lymphangioma, 188 
Temperature of dead body, 120 
Tendon-sheaths, ganglia of, 911 

inflammations of, 911 
Tenosynovitis, 911 

gonorrheal, 808 
Terata, 246, 251 
Teratoid tumors, 246, 248 
Teratology, 246 
Teratoma, 246 

definition of, 246 

etiology of, 247 

of kidneys, 780 
70 



INDEX 1105 

Teratoma of pia-arachnoid, 932 
Terminal infection, 267 
Test, Schick, in diphtheria, 300 
Testicles, adenosarcoma of, 868 

anatomical considerations, 861 

atrophy of, 862 

benign fungus of, 864 

calcification of, 863 

carcinoma of, 868 

caseation of, 863 

chondroma of, 867 

chorioepithelioma of, 868 

congenital abnormalities, 862 

dermoid cysts of, 869 

echinococcus cysts of, 869 

endothelioma of, 868 

fatty degenerations of, 862 

fibroma of, 867 

hyperemia of, 863 

hypertrophy of, 862 

inflammation of, 863 

lepra of, 867 

mixed tumors of, 867 

myxomatous degeneration of, 863 

physiological considerations, 861 

sarcoma of, 867 

syphilis of, 867 

tuberculosis of, 866 

tumors of, 867 
Tetanolysin, 325 
j Tetanospasmin, 325 
Tetanus, 323 

antitoxin, 325 

bacillus of, 323 

definition of, 323 

etiology of, 324 

pathological anatomy, 325 
physiology, 325 
Texas fever of cattle, 393 
Thelitis, 875 
Thoracic duct, 547 
dilatation, 547 
inflammation of, 548 
thrombosis, 547 
tuberculosis of, 548 
tumors, 548 
Thrombi, 73 

ball, 76, 488 

globular, 488 

hyaline, 78, 93 

lateral, 76 

marantic, 73 

obstructive, 76 

primary, 75 

secondary, 75 

stratified, 75 

white, 74 

yellowish, 74 
Thrombin, 74 

Thrombo-angiitis obliterans, 527 
Thrombophlebitis, 543 
I Thrombosis, 73 

alterations in blood as cause, 74 

in blood-current as cause, 73 
calcification after, 77 
canalization of, 78 
causes of, 73 

changes in vessel walls as cause, 73] 
effects of, 76 



1106 



INDEX 



Thrombosis, ferment, 74 
of bones, 889 
of braim 957 
of cavities of heart, 487 
of coronary artery, 489 
of mesenteric arteries, 662 
of portal vein, 688 
of renal veins, 755 
of splenic vein, 461 
of thoracic duct, 547 
of veins, 912 
organization from, 77 
pathological anatomy, 74 
subsequent changes in, 76 
Thrush, 364, 626, 640 

fungus, 365 
Thymic asthma, 748 
Thymus gland, anatomy and develop- 
ment, 747 
circulatory disturbances, 748 
congenital abnormalities, 747 
inflammation of, 748 
syphilis of, 748 
tuberculosis of, 748 
tumors of, 748 
Thyreoglobulin, 735 
Thyroid disease, general results of, 741 
gland, abscess of, 736 
actinomycosis of, 741 
adenoma of, 741 
anatomical considerations, 735 
carcinoma of, 741 
circulatory disturbances of, 735 
congenital defects, 735 
hyperemia of, 735 
inflammation of, 736 
parasites of, 741 
sarcoma of, 741 
syphilis of, 741 
tuberculosis of, 740 
tumors of, 741 
Thyroiditis, 736 

acute suppurative, 736 
Thyroxin, 735 
Tinea, 1054, 1055 
circinata, 367, 1054 
sycosis, 367, 1055 
tonsurans, 367, 1054 
versicolor, 367 
Tissue changes, progressive, 163 
destruction, excessive, 44 
elasticity, decreased, as cause of 
edema, 79 
Tongue, atrophy of, 626 
black, 626 

geographical, 365, 623 

inflammation of, 622. See also 
Glossitis. 

large, 622 

strawberry, 623 

tubercle of, 627 
Tongue-tie, 622 
Tonsillitis, 632 

catarrhal, 633 

follicular, 633 

lacunar, 633 

pathological physiology of, 634 
phlegmonous, 633 : ? 
Tonsils, abscess of, 633 



Tonsils, congenital malformations of, 
630 

hypertrophy of, 633 

tuberculosis of, 635 
Tophi, gouty, 49, 909 
Toxalbumins, 261 

from plants, poisoning from, 36 
Toxic cirrhoses, 703 

enteritis, 664 

products of bacteria, 36 
effect of, 264 
Toxin, 268 

immunity, acquired, 273 
natural, 272 
Toxins of bacteria, 261 
fate of, 262 

bacterial, 39 
Toxophore, 268 

group, 276 
Trachea, 555 

carcinoma of, 556 

circulatory disturbances, 555 

infectious diseases, 556 

inflammation of, 556 

malformations of, 555 

sarcoma of, 556 

syphilis of, 556 

tuberculosis of, 556 

tumors of, 556 
Trachoma, 380 

bodies, 1015 

of conjunctiva, 1015 
Transitional leukocytes, 432 
Transmissible diseases, 40 
Transplantation of tumors, 168 
Transverse myelitis, without local foci, 

secondary to injury or infectious dis- 
ease, 988 
Traumatic gangrene, 328 

hemorrhage, 66 

porencephaly, 968 

theory of carcinoma, 230 
Traumatism in etiology of disease, 24 
Trematodes, 397 
Trench fever, 371 

mouth, 624 
Treponema pallidum, 352 
Trichinella spiralis, 412 
Trichiniasis, 413 
Trichobacteria, 257 
Trichoepithelioma, 238 
Trichomonas caudata, 386 

elongata, 386 

flagellata, 386 

intestinalis, 385 

vaginalis, 385 
Trichophyton, 367 
Trichorrhexis, 1059 
Trichuris trichiura, 417 
Trilocular heart, 485 
Trophic derangements in necrosis, 111 
Truncus arteriosus, 484 
Trypanosoma, 387 

brucei, 387, 388 

equiperdum, 387 

evansi, 387 

gambiense, 387, 388 

lewisi, 387, 388 

rougeti, 387 



INDEX 



1107 



Trypanosoma, transmission of, 388 
Trypanosomiasis, 975 
Tubal abortion, 848 

mole, 848 

pregnancy, 848 
Tubercle, 332 

bacillus, 332. See also Bacillus tuber- 
culosis. 

bovine, of pearl disease, 150 

foreign body, 149 

lymphoid, 147 

miliary, 337 

of human form, 150 

of skin, 1045 

of tongue, 627 

structure and evolution, 147 
Tubercula dolorosa, 220 
Tubercular leprosy, 345 
Tuberculin, 341 
Tuberculosis, 147, 332 

avian, 343 

bovine, 336 

bronchogenic, 591, 592 
complications in, 599 

definition of, 332 

etiology of, 332 

fowl-, 343 

gallinarum, 343 

healing of lesions, 339 

hematogenic, 591, 600 

intra-uterine transmission, 336 

latent, 340 

lymphogenic, 591, 603 
miliary, 339 

chronic, 602 

general, 600 
of arteries, 536 
of bladder, 795 
of bones, 897 
of brain, 968 
of bronchi, 561 
of choroid, 1026 

plexus, 972 
of ciliary body, 1025 
of conjunctiva, 1017 
of cornea, 1020 
of dura mater, 922 
of esophagus, 640 
of external ear, 1034 
of Fallopian tubes, 846 
of heart, 518 
of intestines, 678 
of iris, 1024 
of joints. 909 

etiology, 909 

pathological anatomy, 909 

secondary disorders, 910 
of kidney, 779 
of larynx, 553 
of liver, 704 
of lungs, 591 
of lymphatic glands, 472 
individual groups, 474 

vessels, 547 
of mammary glands, 877 
of middle ear, 1038 
of mouth, 627 
of muscles, 918 
of nasal cavities, 550 



Tuberculosis of nerve-trunks, 1010 
of optic nerve, 1031 
of ovaries, 835 
of pancreas, 723 
of pelvis of kidney, 790 
of penis, 860 
of pericardium, 522 
of peritoneum, 730 

pathological anatomy, 731 
of pharynx, 635 
of pia-arachnoid, 980 
of placenta, 857 
of pleura, 618 
of prostate, 870 
of retina, 1028 
of seminal vesicles, 874 
of skin, 1053 
of spinal cord, 992 
of spleen, 466 
of suprarenal bodies, 745 
of testicles, 866 
of thoracic duct, 548 
of thymus gland, 748 
of thyroid gland, 740 
of tonsils, 635 
of trachea, 556 
of tympanic membrane, 1035 
of urethra, 810 
of uterus, 822 
of vagina, 851 
of vas deferens, 867 
of veins, 545 
of vulva, 853 

pathological anatomy, 337 

physiology, 341 
pneumonic, 593 

acute, 594 

chronic, 595 
progression of, 339 
relation of human to animal, 336 
seats of, 339 
Tuberculous arthritis, 909 
cirrhosis, 703 
meningitis, 928, 975 

pathological anatomy, 928 
pachymeningitis, external, 978 
pleuritis, 618 
pneumonia, 582 
Tubo-ovarian cysts, 847 
Tumors, 164 

bacteria and, connection between, 

168 
benign, 174 

blastomycetes in cause of, 169 

chemical constitution, 173 

chromaffin, 217 

circumscribed, 171 

classification of, 175 

Cohnheim's theory, 166 

connective-tissue, 176 

defective development as cause, 166 

definition of, 164 

dyscrasia, 230 

epithelial, 223, 1056 

of lung, 607 
etiology of, 165 

external irritation as cause, 166 
from nerve tissues, 213 
gummy, 355 



1108 

Tumors, Hansemann's theory, 167 
Hauser's theory, 167 

Adami's modification, 167 
infectious character, 167 
infiltrating, 171 
malignant, 174 
metastasis of, 174 
mixed, 248 
number of, 172 
of biliary tract, 716 
of bladder, 797 
of bone-marrow, 483 
of brain, 969 
of bronchi, 561 
of choroid, 1026 

plexus, 973 
of ciliary body, 1025 
of conjunctiva, 1018 
of cornea, 1020 
of dura mater, 922, 979 
of esophagus, 640 
of external ear, 1035 
of eyelids, 1032 
of Fallopian tubes, 846 
of heart, 518 
of intestines, 680 
of iris, 1024 
of joints, 911 
of kidneys, 780 

secondary, 783 
of larynx, 554 
of liver, 706 
of lungs, 606 
of lymphatic glands, 478 

vessels, 547 
of middle ear, 1038 
of mouth, 628 
of muscles, 9] 9 
of nails, 1059 
of nasal cavities, 551 
of nervous system, 1011 
of optic nerve, 1031 
of orbit, 1031 
of ovaries, 835 
of pancreas, 723 
of parotid gland, 637 
of pelvis of kidney, 791 
of pericardium, 523 
of peritoneum, 732 
of pharynx, 636 
of pia-arachnoid, 981 
of pituitary body, 750 
of pleura, 619 
of prostate, 872 
of retina, 1028 
of sebaceous glands, 1058 
of skin, 1056 
of spinal cord, 1005 
of spleen, 466 
of stomach, 651 
of suprarenal bodies, 747 
of testicles, 867 
of thoracic duct, 548 
of thymus gland, 748 
of thyroid gland, 741 
of trachea, 556 
of urethra, 810 
of uterus, 824 
of vagina, 852 



INDEX 

Tumors of veins, 545 
parasitic theory, 168 
pathological physiology, 172 
predisposing conditions, 169 
primary, 172, 175 
Ribbert's theory, 167 
secondary, 172, 175 
shape of, 171 
structure of, 170 
svnonyms of, 164 
teratoid, 246, 248 
transplantation of, 168 
Virchow's theory, 166 
Tympanic membrane, 1035 
Typhase, 272 
Typhlitis, 666 
Typhoid fever, 303, 672 
agglutination in, 307 
bacillus of, 303 
carriers, 306 
complications, 676 
definition, 303 
etiology, 303 

Gruber-Durham phenomenon in, 
307 

lesions in other parts complicating, 
677 

pathological anatomy, 306, 672 

physiology, 307 
Widal reaction in, 307 
septicemia, 303 
ulceration of esophagus, 640 
Typhus fever, 375 
icteroides, 369 
recurrens, 357 
Tyroma, 929 
Tyrosin in urine, 806 

Ulcer, 139 

gastric, 646 

indolent, 140 

of bronchi, 558 

of skin, 1053 

peptic, 140, 646 

perforating, of foot, 140 

phagedenic, 140 

round, 646 

of stomach, 140 

serpiginous, 140 
Ulceration of cervix, phagedenic, 820 

typhoid, of esophagus, 640 
Ulcerative endocarditis, 492 

enteritis, 664 

esophagitis, 638 

gastritis, 643 

keratitis, 1019 

stomatitis, 624 
Ulcus exdigestone, 646 
Ultraviolet rays in etiologv of disease, 31, 

32 

Umbilical cord, abnormalities of develop- 
ment, 855 
velamentous insertion of, 855 
Uncinaria americana, 415 

duodenalis, 413 
Uncinariasis, 415 
Unguis incarnatus, 1059 
! Uniceptors, 277 
i Unna's plasma-cells, 129 



INDEX 



1109 



Ununited fracture, 888 
Upward dislocation of uterus, 813 
Urates in urine, 805 
Uratic infarct, 104 

infiltration, 104 
Ureter, dilatation of, 786 

malformations of, 786 

obstructions of, 786 

parasites of, 791 
Ureteritis, 790 
Urethra, carcinoma of, 810 

congenital abnormalities, 806 

cysts of, 810 

inflammation of, 807. See also U 
thritis. 

injuries of, 809 

polypoid tumors of, 810 

sarcoma of, 810 
' stricture of, 809 

syphilis of, 810 

tuberculosis of, 810 

tumors of, 810 
Urethritis, 807 

anterior, 808 

chronic, 809 

gonorrheal, 810 

lesions associated with, 808 

pathological anatomy, 808 

posterior, 808 
Uric acid in urine, 804 
Urinary calculi in bladder, 795 
results of, 797 

diseases of, 753 
Urine, abnormal conditions of, 799 

amount of daily excretion, 758 

bilirubin in, 806 . 

carbonates in, 806 

chemical changes in, 804 

cholesterin in, 806 

color of, 799 

cystin in, 806 

fat-crystals in, 806 

hematoidin in, 806 

hemoglobin in, 806 

hippuric acid in, 806 

indigo in, 806 

leucin in, 806 

methemoglobin in, 806 

oxalate of lime in, 804 

phosphates in, 805 

quantity of, 799 

reaction of, 800 

sediments in, 804 

specific gravity, 799 

sulphates in, 806 

tyros'in in, 806 

urates in, 805 

uric acid in, 804 

xanthin in, 806 
Uriniferous tubules, concretions in, 
779 

Urobilinuria, 801 

Urticaria, 1045 

Uterus, adenoma of, 828 

alterations of position, 812 

amyloid infiltration of, 824 

anatomy of, 811 

anteflexion of, 812 

anteversion of, 812 



Uterus bicornis, 811 
carcinoma of, 830 
congenital abnormalities, 811 
cysts of, 833 
development of, 811 
dilatation of, 815 
duplexus, 812 
erosions of, 820 
fatty degeneration of, 824 
fibroids of, 824 
hemorrhages from, 816 
hyperemia of, 815, 816 
hyperplasia of mucous membrane of, 
824 

hypertrophy of, 824 

infantilis, 811 

infectious diseases of, 820 

inflammation of, 817 

inversion of, 814 

involution of, 83 

lateral displacements of, 813 

leiomyoma of, 824 

myofibroma of, 824 

parasites of, 833 

polypi of, 824 

prolapse of, 813 

puerperal atrophy of, 823 

retroflexion of, 812 

retroversion of, 813 

rupture of, 815 

sarcoma of, 827 

senile atrophy of, 823 

septus, 811 

stenosis of, 815 

syphilis of, 823 

tuberculosis of, 822 

tumors of, 824 

unicornis, 812 

upward dislocation of, 813 
Uveal tract, hyperemia of, 1023 
Uveitis, 1025 

serous, 1024 

Vaccinia, 373 

Vacuolation of erythrocytes, 437 
Vacuolization, 944 
Vagina, carcinoma of, 852 
1 cysts of, 852 

fibroma of, 852 

fistulse of, 850 

hemorrhages into, 850 

hyperemia of , 850 

inflammations of, 850. See also 
Vaginitis. 

myofibroma of, 852 

papilloma of, 852 

sarcoma of, 852 

stenosis of, 849 

syphilis of, 852 

tuberculosis of, 851 

wounds of, 850 
Vaginal cystocele, 849 

rectocele, 849 

walls, prolapse of, 849 
Vaginitis, 850 

acute catarrhal, 850 

aphthous, 851 

catarrhal, acute, 850 
chronic, 851 



1110 

Vaginitis, emphysematous, 851 
erysipeloid, 851 
exfoliative, 850 
pseudomembranous, 850 
senile, 851 
testis, 863, 864 
hemorrhagic, 865 
purulent, 865 
serofibrinous, 865 
Valvular aneurysm, 517 

defects of heart, 487 
Varicella, 375, 1047 
Varicocele, 866 
Varicose aneurysm, 542 

veins of spinal cord, 986 
Varicosity, 544 
Variola, 373, 1047 
Varix, aneurysmal, 542 
Vas deferens, inflammation of, 866 

tuberculosis of, 867 
Vascular goiter, 737 

theories of inflammation, 122 
tissues, phenomena of inflammation 
in, 122 

Vasomotor disturbances, 61 
Vaughan's theory of anaphylaxis, 284 
Vegetable parasites in blood, 458 

of intestines, 684 
Vein-stones, 544 
Veins, 542 

anatomical considerations, 542 

calcification of, 542 

dilatation of, 544 

fatty degeneration, 542 

infectious diseases, 545 

inflammation of, 542. See also 
Phlebitis. 

syphilis of, 545 

thrombosis of, 912 

tuberculosis of, 545 

tumors of, 545 
Venereal wart, 223 
Venom, insect, poisoning from, 37 

snake, poisoning from, 37 
Venous hemorrhage, 65 

hyperemia, 63 
Ventricles, ependymitis of, 973 
Ventricular extrasystoles, 506 

septum, defects of, 486 
Vermes, 397 

Vernal conjunctivitis, 1014 
Verrucse, 1042 
Verrucose endocarditis, 491 
Vesica bipartitis, 792 
Vesicles, 1045 

Vesicular emphysema of lungs, 568 
v-granules, 434 
Vibrio cholerse asiaticse, 347 
Vibrion septique, 329 
Vicarious emphysema of lungs, 568 
Vincent's angina, 358, 624, 635 
Virchow's theory of inflammation, 122 

of tumors, 166 
Viruses, filterable, 369 
Vitamins, 41, 59 
Vitiligo, 1044 

Vitreous degeneration of heart, 501 
humor, 1013, 1022 

chemical changes in, 1022 



INDEX 

Vitreous humor, hemorrhage into, 1022 

inflammation of, 1022 
Volvulus of intestines, 659 
von Jaksch's disease, 457 
von Recklinghausen's disease, 218 
Vulva, abscess of, 853 
adenoma of, 854 
anomalies of, 852 
carcinoma of, 854 
caruncle of, 854 
chancroids of, 854 
cysts of, 854 
diphtheria of, 853 
edema of, 852 
elephantiasis of, 854 
fibroma of, 854 
fibromyxoma of, 854 
gangrene of, 854 
hematoma of, 853 
hyperemia of, 852 

inflammation of, acute catarrhal, 853 
chronic, 853 
phlegmonous, 853 
lipoma of, 854 
myofibroma of, 854 
papillomatous tumors of, 854 
i sarcoma of, 854 
syphilis of, 853 
tuberculosis of, 853 
Vulvitis, 853 

Waldeyer's plasma-cell, 129 
Warts, 224, 1042 

venereal, 223 
Water transmission of disease, 425 
Weak heart, 60 
i Weil's disease, 359 
Wens, 243, 1058 
Whip-worm, 417 

White corpuscles, 431. See also Leuko- 
cytes. 
infarct, 71 

matter of spinal cord, degenerations in, 
1000 

softening of brain, 958 
swelling, 910 
thrombi, 74 
Whooping-cough, Bordet-Gengou bacil- 
lus of, 318 
Widal reaction in typhoid fever, 307 
Widal-Gruber reaction, 272 
Wilm's tumor, 783 
Wilson's disease, 964 
, Winogradsky's nitrosomonas, 261 
Wool-sorters' disease, 326, 328 
Wounds of choroid, 1025 
of cornea, 1020 
of heart, 518 
of vulva, 852 
repair of, 143 
tissue changes from, 24 

! Xanthin in urine, 806 
1 Xanthoma, 182, 1056 
definition of, 182 
diabeticorum, 182 
palpebrarum, 182 
structure of, 182 
vulgare, 182 



Xerosis, 1016 

X-rays in etiology of disease, 31 
Yaws, 358, 1054 

Yellow atrophy of liver, acute, 691 
fever, 369 

definition, 369 
etiology, 369 

pathological anatomy, 370 



INDEX 1111 

Yellow fever, pathological physiology, 370 
role of mosquitoes in, 369 
softening of brain, 958 
Y-granules, 434 

Zenker's hyaline, 94 

change, 306 
Zuckergussleber, 703, 730 
Zymophore, 268 



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